The Pharmacologist June 2016

the

A Publication by The American Society for Pharmacology and Experimental Therapeutics

Pharmacologist Vol. 58 • Number 2 • June 2016

Taxol:

Barking Up the Right Tree

Inside: Farewell Message from the President 2016 Annual Meeting in Review Call for 2017 Award Nominations

The Pharmacologist is published and distributed by the American Society for Pharmacology and Experimental Therapeutics.

Contents 67 Message from the President 69 2016 Annual Meeting in Review 81 Call for 2017 Award Nominations 84 Feature Story: Taxol: Barking Up the Right Tree 96 Meeting News 101 Science Policy News 107 Education News 110 Journals News 112 Membership News Obituaries: Dale Louise Birkle Dreer Nancy Rutledge Zahniser

118 Members in the News 120 Division News 130 Chapter News

THE PHARMACOLOGIST PRODUCTION TEAM Rich Dodenhoff Catherine L. Fry, PhD Dana Kauffman Judith A. Siuciak, PhD Suzie Thompson COUNCIL President Kenneth E. Thummel, PhD President-Elect David R. Sibley, PhD Past President Annette E. Fleckenstein, PhD Secretary/Treasurer Dennis C. Marshall, PhD Secretary/Treasurer-Elect Charles P. France, PhD Past Secretary/Treasurer Paul A. Insel, MD Councilors Wayne Backes, PhD John D. Schuetz, PhD Margaret E. Gnegy, PhD Chair, Board of Publications Trustees Mary E. Vore, PhD Chair, Program Committee Scott Waldman, MD, PhD FASEB Board Representative Brian M. Cox, PhD Executive Officer Judith A. Siuciak, PhD The Pharmacologist (ISSN 0031-7004) is published quarterly in March, June, September, and December by the American Society for Pharmacology and Experimental Therapeutics, 9650 Rockville Pike, Bethesda, MD 20814-3995. Annual subscription rates: $25.00 for ASPET members; $50.00 for U.S. nonmembers and institutions; $75.00 for nonmembers and institutions outside the U.S. Single copy: $25.00. Copyright Š 2016 by the American Society for Pharmacology and Experimental Therapeutics Inc. All rights reserved.

Periodicals postage paid at Bethesda, MD. GST number for Canadian subscribers: BN:13489 2330 RT. ASPET assumes no responsibility for the statements and opinions advanced by contributors to The Pharmacologist.

Postmaster: Send address changes to: The Pharmacologist, ASPET, 9650 Rockville Pike, Bethesda, MD 20814-3995.

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Message from

The President My Fellow Pharmacologists, With the close of another highly successful ASPET Annual Meeting at Experimental Biology (EB) in San Diego in April, my term as President of the American Society for Pharmacology and Experimental Therapeutics (ASPET) is coming to an end. I think we have accomplished much together that I hope has strengthened the society and helped secure its future.

At the outset, I want to thank Dr. Judy Siuciak, ASPET Executive Officer, and all of the ASPET office staff for their superb and dedicated attention to the operations of the society, including most importantly the Experimental Biology meeting, and the support that they provided to me during the past 12 months.

Some of the accomplishments that I would like to highlight played out at EB2016. They include an increase in the number of travel awards made to post-doctoral fellows, graduate and undergraduate students, some of which were supported by the BIG IDEAS project on Enhancing Undergraduate Engagement in ASPET at EB Meetings, an initiative led

by Dr. Carol Beck and Dr. Catherine Davis. Enhancing the attendance of young scientists at EB is one way in which ASPET can support their careers and foster a lasting relationship between them and the society. An ASPET Mentoring Network was established and, at EB2016, there was an inaugural meeting/workshop of “coaches” and “mentees” that is part of the funded BIG IDEAS project – From Senior Mentor to Highly Skilled Career Coach: A Novel Approach to Breaking the Diversity Roadblock, led by Dr. Lynn Wecker and Dr. Susan Ingram. ASPET is also launching this Summer the Pharmacology Industry Internships for PhD Students (PIIPS) program, which will be overseen by ASPET staff with support from Dr. Kay Meier and a PIIPS steering committee. This program is intended to provide graduate students with an industry-based research experience that can help shape critical career decisions. In addition, during its Spring meeting at EB2016, ASPET Council approved funding of a new BIG IDEAS initiative, Surmounting the Insurmountable: Obstacles in Drug Discovery and Development – Real World Case Studies. It will be led by Dr. Kan He, Dr. Tom Woolf and Dr. Paul Hollenberg, as well as other members from the academic and industrial communities. A major goal of this new initiative will be to teach beginning pharmacologists, through discussion of case studies, how to think critically to solve biochemical, pharmacological and pharmaceutical problems that can arise during the discovery and development of new therapeutic agents.

Other educational and mentoring events at EB2016 that bear mentioning include the Undergraduate Research: Cultivating the Next Generation of Researchers Through SURF and Beyond Symposium, with presentations from current institutional SURF directors, individual mentors and truly inspiring talks by past recipients of a SURF award (Natalie Arabian, USC; Chelesa Fearce, Spelman College; and Michael Little, UNC-Chapel Hill) who clearly illustrate how transformative this form of financial support and mentoring can be for emerging young research scientists. Of note, the ASPET SURF program has been in existence since 1992 (25th anniversary in 2017) and has supported research experiences for over 2000 undergraduates. A SURF task force was formed last year to evaluate its performance outcomes and to chart future directions; early results of that analysis suggest remarkable success in fostering careers in the allied health sciences, including pharmacology. ASPET also held for the first time at EB2016 the Undergraduate Networking and Career Development Luncheon, with presentations by Dr. Janet Clark, director for fellowship training at the National Institutes of Mental Health and Dr. Alexandra Newton, professor of pharmacology at the University of California, San Diego. The Graduate Student-Postdoctoral Colloquium featured a provocative and well-received presentation by Dr. Rick McGee, associate dean for faculty recruitment and professional development at Northwestern University, on “Mentoring Your Mentor.”

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68 EB2016 also marked the inaugural in-person meeting of the ASPET Young Scientists Committee (YSC), led by Dr. Karen Tonsfeldt, and predoc/post-doc members representing a variety of divisions and other committees. This committee was formed to give young pharmacologists a stronger voice in setting the agenda of our society and to provide them with opportunities for leadership and career development. One of the first accomplishments of the committee was the development and submission of symposium proposals to be considered for EB2017 programming.

They also reached out to their brethren attending EB2016, through the YSC Photo Booth, to build camaraderie among the young scientists attending the meeting and elicit feedback for focusing future efforts of the committee in the coming year. One of the ideas that is being considered is a plan for the Young Scientists Committee and the Mentoring and Career Development Committee to collaborate on an outreach event for the local (Chicago) K-12 and undergraduate community to foster an interest in the sciences, a basic understanding of the field of pharmacology, and how research in this area can benefit society.

Each of these educational and mentoring initiatives and EB events benefited greatly from the superb support and leadership of Dr. Catherine Fry and Carla Burns in the ASPET office, and were implemented as part of a long-term strategy that I supported at the outset of my presidency to foster development of the next generation of pharmacologists and leaders of ASPET. For those of you who couldn’t make the EB meeting this year, we were delighted to help celebrate the 50th anniversary of PhRMA by recognizing during the Business Meeting their long history of financial support for ASPET members (specifically its young scientists) and reminiscing on that incredible relationship during a joint reception that followed. The San Diego weather that evening was wonderful, as advertised, and contributed to an incredible ambience and heightened level of enthusiasm for events that took place over the next four days. As always, the EB meeting was filled with stimulating lectures from society members and other invited speakers, in particular those special presentations given by winners of the major ASPET society awards.

As President of ASPET, I was honored to host the Presidential Symposium on a topic of personal scientific interest – Precision Medicine in Anti-Cancer Pharmacology. Read more about this event on page 74.

Introduction of the BIG IDEAS initiatives during the last year, with their focus on education and mentoring of the next generation of pharmacology leaders, prompted further introspection by Council and resulted in a decision to embark on a thorough and comprehensive strategic planning process that will determine who we are, where we want to be in the next 5 and 10 years, and how we will get there. This challenging but necessary exercise will be overseen by my successors, Dave Sibley (president-elect) and John Schuetz (president-elect-elect), our Executive Officer Judy Siuciak, and the rest of ASPET Council and office staff. I strongly encourage you to participate in our strategic planning when called upon for input through planned surveys and other data collection and feedback mechanisms.

In closing, I want to express to the ASPET membership my sincere thanks for bestowing on me the distinct honor to serve as president of the Society. It has been an incredible experience, one filled with wonderful memories that I will cherish always.

Kenneth E. Thummel ASPET President

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2016 ANNUAL MEETING

IN REVIEW

The ASPET Annual Meeting at Experimental Biology 2016 took place on April 2–6, 2016 in San Diego, CA. With over 12,000 attendees at EB, members enjoyed a successful meeting experience with an excellent scientific program and great networking and social events.

This year’s business meeting took place on Saturday, April 2 led by President Ken Thummel from the University of Washington. Dr. Thummel updated members on the Society’s current activities, programs, and initiatives. Highlights from his presentation included: • The Otto Krayer Award •A n update on the member-driven BIG IDEAS initiatives • A summary of ongoing global pharmacology partnerships • A review of the ASPET Summer Undergraduate Research Fellowship (SURF) program • ASPET’s increased undergraduate opportunities • Highlights of the EB2016 meeting including the inaugural programming for the Division for Cancer Pharmacology • Improved member communications A report on ASPET’s financial status was presented

by Secretary/Treasurer Dennis Marshall, and a presentation on ASPET’s journals was given by Board of Publications Trustees Chair Mary Vore. Directly

following the business agenda, Dr. Thummel was honored to present awards to this year’s scientific achievement award winners and travel award winners.

Incoming President David Sibley thanks President Ken Thummel for his services.

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“Thank you for organizing such a great meeting. It was amazing.”

–Peggy Gnegy 4

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(1) 2016 ASPET Scientific Achievement Award Winners (2) 2016 P.B. Dews Lifetime Achievement Award winners Roy W. Pickens and Travis Thompson with President Ken Thummel.

(3) 2016 Undergraduate Student Travel Award Winners (4) 2016 ASPET Graduate Student Travel Award Winners (5) 2016 ASPET Young Scientist Travel Award Winners (6) 2016 Washington Fellows (7) 2016 Mentoring Network participants

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71 This year’s opening reception was held jointly with the PhRMA foundation to honor their 50th anniversary. Over 400 people gathered in the open terrace of the San Diego Convention Center to celebrate the start of the annual meeting. Members enjoyed great food, perfect San Diego weather, and a lively atmosphere to catch up with old and new friends.

President Ken Thummel presents a 50 year anniversary gift to PhRMA Foundation’s Eileen Cannon and Terry Bowlin.

2016 ASPET Opening Reception

The ASPET booth in the exhibit hall was very successful this year. We recruited 70 new members, including 8 regular members, 3 postdoc members, 41 graduate student members, and 18 undergraduate student members. We also offered a new t-shirt for sale in our store, which was our highest selling item. If you didn’t get a chance to purchase an ASPET product at the meeting, you can make purchases online at www.aspet.org/store.

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72 New this year, the ASPET member lounge was a huge hit with members in the session hall. We offered members morning coffee, free Wi-Fi, and a place to relax between sessions. The Meet-a-Mentor sessions, Meet-the-Editor sessions, and the ASPET Young Scientist Committee’s photo booth were hosted in the lounge.

Poster Competition

Meet-a-Mentor session in the member lounge

The 2016 Student and Postdoctoral Poster Competition gave students and young scientists an opportunity to present their work in a lively and fun atmosphere. ASPET divisions held their competitions simultaneously and allowed students to talk about their work and network with senior members, colleagues, and friends. The ASPET divisions presented their award winners with cash prizes and award certificates.

To learn who won the division competitions, please turn to the division news section on page 120.

Meet-the-Editor session in the member lounge

“I found it [the new members lounge] so helpful in catching my breath, organizing my thoughts and planning my next stop, as the week progressed.”

– Ken Thummel

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73 The 2016 Dolores C. Shockley Best Presentation Awards were given out at the Student and Postdoctoral Poster Competition. Dr. Shockley was the first African American woman to earn a PhD in pharmacology and the first black woman appointed to chair a pharmacology department in the US.

In the graduate student category, prizes were awarded to Jenaye Robinson (1st) from Texas Southern University, Dominique Jones (2nd) from University of Louisville, and Antoinette Nelson (3rd) from Rutgers University. In the postdoctoral scientist category, prizes were awarded to Rheaclare Fraser-Spears (1st) from the University of Texas Health Science Center, San Antonio and Inigo Valiente-Alandi (2nd) from the Cincinnati Children’s Hospital Medical Center.

ASPET Student/ Postdoc Mixer

Following the poster competition, ASPET students and postdocs socialized at the Student/Postdoc Mixer.

The mixer was packed with members dancing and having fun with friends.

To view the full album of EB2016 pictures, visit us online at: http://bit.ly/1rU8yeo June 2016 • The Pharmacologist

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Annual Meeting Highlights ASPET Presidential Symposium: Precision Medicine in Anti-Cancer Pharmacology The ASPET Presidential Symposium was held on Sunday, April 3 and chaired by Dr. Ken Thummel, ASPET President, and Dr. Susan Cole, chair of the newly constituted Division for Cancer Pharmacology (DCP); DCP was also a co-sponsor of the symposium. We were incredibly fortunate to have outstanding presentations from Dr. Jun Yang at St. Jude Children’s Research Hospital on Thiopurine Pharmacogenetics: From Mechanism to Clinical Action; Dr. Eileen Dolan at the University of Chicago on Genome-Wide Studies of Chemotherapeutic Associated Toxicities; Dr. Mary-Ann Bjornsti at the ASPET President Ken Thummel, with speakers of the ASPET Presidential Symposium during the annual meeting at EB2016.

University of Alabama-Birmingham on Yeast Phenomics: Lessons in Cancer Precision Medicine Initiative and represents an Therapy; and Dr. Liewei Wang at the Mayo Clinic on opportunity for pharmacology to shape the future of Breast Cancer Pharmacogenomics: Application of medicine.

PDX Model. Each presentation highlighted how basic The next Presidential Symposium titled ASPET discovery of the genetic and environmental basis for inter-individual differences in drug efficacy and toxicity Presidential Symposium: Leveraging New Paradigms for GPCR Drug Discovery will be chaired by Presidentmight be harnessed and translated into prospective Elect Dr. Dave Sibley. The symposium will be held at tests that guide clinical decisions and improve the the ASPET Annual Meeting at EB2017 in Chicago. outcomes of pharmacological interventions in the treatment of cancer. This is a focus of the national

ASPET Journals Symposium: Hear It from the Editors—Navigating the Course through Journal Submission and Publication EB 2016 saw the first symposium by ASPET’s journals and co-sponsored by the Board of Publication Trustees (BPT) and all of ASPET’s divisions. The meeting was created as a practical guide for earlycareer scientists and focused on publishing in ASPET’s journals. The presentations highlighted how to write a competitive manuscript, how to effectively deal with

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rejection and revision decisions, and how publication ethics and accountability, among other topics, are applicable to publishing in all research journals. The panel included current and recent editors of the Society’s journals.

Mary Vore, professor emerita in the Department of Toxicology and Cancer Biology at the University

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of Kentucky College of Medicine and chair of the BPT, discussed how to choose a journal for your manuscript. She noted the many competing journals in pharmacology and related fields and highlighted the advantages of publishing in one of the ASPET’s journals. In examining the scope of each journal, Dr. Vore showed the breadth of pharmacology research published by the Society.

Michael F. Jarvis, Volwiler Senior Research Fellow and senior scientific director at AbbVie Inc., served as the editor of The Journal of Pharmacology and Experimental Therapeutics from 2010 to 2015. He addressed the question of how to write a competitive manuscript. There are many resources available, and researchers can benefit from seeking guidance from their academic institutions, scientific societies, journals themselves, and even commercial vendors. Guidelines and checklists providing best practices are available online and cover clinical and preclinical research.

He highlighted that many have been developed to enhance the reproducibility of published research.

Dr. Jarvis described the elements that are critical to a successful manuscript, which start with an important and clear hypothesis. This should be supported by dose-response determinations, positive and negative controls, validated reagents, and sufficient power and appropriate statistical analysis. A detailed and rigorous analysis of the study’s results and limitations should conclude the manuscript. His presentation went

through the sections of an article and examined the purpose and goals of each as well as explaining the effective use of figures and figure legends.

Edward T. Morgan, professor of pharmacology at the Emory University School of Medicine and editor of Drug Metabolism and Disposition spoke about communicating experimental design and analysis considerations. The lack of reproducibility of scientific literature make clear the need to clearly, thoroughly, and effectively present experimental design. Dr. Morgan noted four causes of irreproducible results: flawed science, bad reagents, bad reporting, and biological variability. He went on to cite six red flags that fall under one or more of these causes.

In addition, he noted the “fascination with P” which include the problems of P-chasing or hacking and the need to use P values with other data to determine the significance of a finding. Dr. Morgan showed how ASPET’s journals have responded to these issues through rigorous requirements given in the Instructions to Authors. These include specific requirements for reporting animal and human experiments. He concluded with clear, detailed recommendations for designing experiments and reporting them.

Stephen Traynelis is a professor in the Department of Pharmacology at the Emory University School of Medicine and editor of Molecular Pharmacology. His presentation went step-by-step through the peerreview process, explaining what happens at each stage, why negative decisions may occur, and what avoidable mistakes can lead to rapid rejection. Dr. Traynelis removed the mystery of the peer review process with a detailed guided tour through what many researchers may consider a hazardous journey.

He presented effective and constructive ways to respond to reviewer comments and an invitation to resubmit with a revised manuscript.

Rich Dodenhoff, ASPET’s journals director, spoke about Speakers of the ASPET Journals Symposium, which took place Monday, April 4 during ASPET’s authorship, accountability, Annual Meeting at EB2016.

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ethics, and copyright. He began with the criteria for authorship and explained that authorship ties closely with accountability and ethics in scientific publishing. In the vein of ethics, he addressed image manipulation, discussing what is and is not allowed. Resources about ethics and accountability are numerous and include the Office of Research Integrity and the US Department of Health and Human Services, the International Committee of Medical Journal Editors, and the Committee on Publications Ethics. He spoke about copyright, starting with an explanation that copyright happens automatically when a work is created in a fixed, tangible form and all that that implies in the reuse of published materials.

Copyright can present confusing problems, but excellent resources are available, including circulars from the US Copyright Office, your institution’s librarians, and the Copyright Clearance Center.

The presentations were followed by a question and answer period facilitated by David Sibley, former editor of Pharmacological Reviews, and Darrell Abernethy, editor-in-chief of Pharmacology Research & Perspectives. Audience members and panelists discussed the issues of revealing the names of reviewers and depositing published papers with filesharing sites, among other topics.

All of the slides from the presentations are available on ASPET’s website at http://bit.ly/1XrvqOc and include links to resources. The Board of Publications Trustees will follow up at next year’s meeting with a more indepth look at some of the topics discussed in these presentations, perhaps incorporating more audience interaction. Stay tuned!

Meet-the-Experts Lunch: Careers in Translational and Clinical Pharmacology During the ASPET Annual Meeting at Experimental Biology 2016 in San Diego, the Division for Translational and Clinical Pharmacology (TCP) hosted its second special session aimed at connecting trainees with experienced scientists to answer questions and provide career advice. This “Meetthe-Experts Lunch” featured clinical and translational pharmacologists within the TCP Executive Committee and ASPET, representing diverse careers in academia, industry, and government, as follows: • Pam Hornby - Senior Scientific Director and Fellow, Janssen Research and Development, J&J Adjunct Professor, Department of Pharmacology and Physiology, Drexel University College of Medicine, Chair of TCP and organizer of the Meetthe-Experts Lunch at EB2016 • James Barrett - Director, Clinical and Translational Research Institute; Professor, Department of Pharmacology and Physiology, Drexel University College of Medicine • Thomas Beveridge - Associate Director, Clinical Science, Medical Affairs, Ferring Pharmaceuticals Inc.; Adjunct Assistant Professor, Department of Physiology and Pharmacology, Wake Forest School of Medicine

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• Ross Corriden - Assistant Project Scientist, Department of Pharmacology, University of California, San Diego • Benedict Green - Research Pharmacologist, Poisonous Plant Research Laboratory ARS/USDA • Michael Holinstat - Associate Professor, Department of Pharmacology School of Medicine, University of Michigan • Dennis Marshall - Executive Director, Medical Affairs, Ferring Pharmaceuticals, Inc. • Jeffrey Paul - Clinical Pharmacology Consultant; Clinical Dev. Adjunct Faculty at Drexel University College of Medicine • Scott Waldman - Professor and Chair, Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University

“Thank you so much for the mentorship and guidance.”

More than 50 TCP and ASPET members attended the invitation only event. The lunch opened with each mentor providing a 3 minute summary of the highlights of their career, with Dr. Hornby putting

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• How easy is it to transition from an academic career to becoming an entrepreneur?

• How to prepare for job interviews in a different environment that I am familiar with?

All attendees gained insight into the diversity of viewpoints on where clinical and translational pharmacology is headed and different ways to prepare for these careers. Mentors also discussed additional training requirements needed to The Division for Translational and Clinical Pharmacology Meet-the-Experts Lunch was held work as a successful clinical Tuesday, April 5 during the ASPET Annual Meeting at EB2016. pharmacologist.

The TCP Division is looking forward to continuing this them on the spot by asking for a single word to “Meet-the-Experts” lunch series at next year’s describe themselves. There were very good personal annual meeting in Chicago. There has already been reflections that came out in those single words such significant email follow up from those who attended, as “determined,” “lucky,” “biomedical,” “persistent,” suggesting that this event helped trainees to identify and “flexible,” which along with the brief career and establish mentoring relationships. Interactions histories, helped the participants to decide which via email and LinkedIn continued after the meeting. mentors to visit. The room was set up for trainees to We encourage interested trainees to consider engage in personal discussions with different mentors. involvement in the TCP Executive Committee to add diversity of membership as graduate or post-doctoral representatives. Typically, trainee representatives “I feel like your career path is closely lead TCP communication efforts. Finally, in response aligned to what I’d like mine to look like.” to many questions about exposure to different research careers, the TCP Division has also invited TCP and ASPET graduate and post-doctoral fellows to Trainees made excellent use of the time with apply for one day site visits to experience Executive questions such as: Committee places of work. The pilot program in the • How is industry research different from academic summer of 2016 will host trainees at Janssen R&D, research?

LLC, Pennsylvania and the ARS/USDA Utah. The • How do I get my foot in the door with industry, TCP Division also put together a new internship should I stay in the same lab for my post-doc as my program in medical affairs at Ferring Pharmaceuticals PhD research?

(Parsippany, NJ), and the inaugural year (2016) • How important is it to publish exclusively in high program is currently in progress. Stay tuned for impact journals or is it more important to have many further exciting opportunities to be initiated by the publications in journals with less impact?

TCP in future!

“This was a great event! Thanks for organizing.

I’m very pleased to see that there is follow-up as well.”

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Debut of the Young Scientists Committee at EB2016 ASPET was excited to introduce the newly formed Young Scientists Committee (YSC) at EB2016. The mission of the YSC is to support the development of future pharmacologists and ASPET members, and to provide leadership experience to trainees in ASPET. ASPET has a long and successful history of recruiting and training young pharmacologists, and the goal of the YSC is to further support these efforts by expanding representation of trainees in committees, unifying trainees among divisions, and communicating with senior ASPET officers.

During the YSC’s inaugural year, the committee had a number of accomplishments. The YSC worked with the Science Policy, Mentoring and Career Development, and Program Committees to have a YSC representative on each. The YSC also submitted two postdoc-chaired symposia proposals for EB2017, and all were highly ranked in their respective divisions. It is the committee’s goal to continue these efforts, and the YSC welcomes ideas for future symposia. Members of the YSC also proposed and staffed the photo booth at EB2016.

They got the word about YSC out to the 70 people who stopped to get their pictures taken. Everyone who participated had a great time, and the 17 YSC members hope to see more attendees stop by next year!

Highlights of YSC member involvement at EB2016 include: • 5 members earned ASPET travel awards • 4 members were selected for the new Mentoring Network: Coaching for Career Development program • 11 posters were presented • 1 poster won an award • 9 members served as poster competition judges • 5 members were division platform speakers and 4 were presentation winners • 8 members served as ASPET/Division committee representatives • 2 members received other societal (non-ASPET) awards • 2 members served as division symposia co-chairs In the first face-to-face committee meeting at EB2016, many new, exciting ideas were discussed for the upcoming year. The YSC’s visions include developing a mentoring system for junior students and first-time attendees at EB, performing community The Pharmacologist • June 2016

outreach in Chicago for the 2017 meeting, spearheading a traineecentered symposium at EB2018, and implementing an easy way to help trainees identify career opportunities at the meeting. Senior leadership at ASPET is excited about the committee’s efforts, and the YSC hopes to have their continued support for its activities moving forward. Stay tuned for further details!

Next year at EB2017 in Chicago, a planned effort between the YSC and the Mentoring and Career Development Committee will focus on community outreach to foster communication between scientists and the lay public. This activity is still under development, but the YSC welcomes participation and suggestions from all ASPET members in this effort. YSC members encourage the involvement of all who are interested!

The YSC will be recruiting interested graduate students and postdocs for the committee in 2017.

Please share your thoughts, enthusiasm, and ideas for the YSC by contacting Karen Tonsfeldt, YSC chair, via info@aspet.org.

Attendees enjoying the Young Scientists Committee photo booth.

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Fun Meeting Facts ASPET debuts the new member lounge

1,072 cups of coffee consumed

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36 yellow mums added color 81 places to sit and relax within the lounge

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144 unique WiFi users on opening day

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2:00PM - 3:00PM

– highest • average number of people in lounge daily

10:00AM - 11:00AM Tuesday

• – greatest attendance in lounge

58 educational and scientific sessions were presented over 5 days Most Attended Sessions: 1. Graduate Student - Postdoctoral Colloquium: Mentoring Your Mentor: Key Skills for Effective Mentoring Relationships with Shared Responsibility 2. Invited Lecture: RhoA in Focus: Pathways from GPCRs to Disease 3. Paul M. Vanhoutte Distinguished Lectureship in Vascular Pharmacology 4. Julius Axelrod Award in Pharmacology Lecture: Therapies of Brain Diseases, Past, Present and Future 5. Invited Symposium: GPCR and RhoA as Mediators of Disease 6. Newly Recognized GPCRs in Health, Disease and as Therapeutic Targets

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Top 3 ASPET items purchased

EB attendees embrace technology

New “Experiment.

Fail. Learn.

Repeat.” t-shirt

Einstein t-shirt

• Plush ASPET donkey

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9,817 total mobile app users 7 ASPET symposia in overall top 10% viewed on mobile app

• ASPET booth in top on the mobile app

ASPET draws pharmacology enthusiasts from around the world!

ASPET attendees at EB represented

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different countries

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10% of booths viewed

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ASPET Awards Now Accepting 2017 Award Nominations ASPET is dedicated to recognizing the best research in, contributions to, and accomplishments in all areas of pharmacology. We encourage members to nominate deserving scientists to raise awareness of the outstanding work being done in our field.

Who can submit a nomination?

You must be an ASPET member to submit nominations. For the Lehr Award, self-nominations from ASPET members are permitted.

Who is eligible to receive awards?

Scientists from all over the world and at all career stages are eligible for ASPET’s various awards. Learn more about the specific eligibility details for each award at http://www.aspet.org/awards/.

How do you submit a nomination?

To nominate someone, visit: http://www.aspet.org/ awards/. Review the award criteria and nomination

requirements. Then log in as a member and select “Go to Awards Portal” to be routed to the nomination forms.

When are nominations due?

The deadline for nominations is Thursday, September 15, 2016 at 5:00 EDT. What happens next?

Each nomination is reviewed by all members of the award’s designated award committee. Scores and rankings are given, and compiled results are discussed by the committee, leading to the final selection of the 2017 awardee.

ASPET Scientific Achievement Awards The John J. Abel Award in Pharmacology is presented for original, outstanding research in the field of pharmacology and/or experimental therapeutics by a candidate who is younger than 45. This award, named after the founder of ASPET, was established in 1946 to stimulate fundamental research in pharmacology and experimental therapeutics by young investigators.

The Julius Axelrod Award in Pharmacology is presented for significant contributions to understanding the biochemical mechanisms underlying the pharmacological actions of drugs and for contributions to mentoring other pharmacologists. This award was established in 1991 to honor the memory of the eminent American pharmacologist who shaped the fields of neuroscience, drug metabolism, and biochemistry and who served as a mentor for numerous eminent pharmacologists around the world.

The Otto Krayer Award in Pharmacology is presented to commemorate the enduring legacy of Otto Krayer’s personal qualities: his ethical behavior, his commitment to teaching, his high standards of scientific scholarship, publication, and editorship, his promotion of interdisciplinary research to reveal the actions of drugs or other chemicals, and his guidance and support of younger scientists. The purpose of the award is to recognize an individual whose character and career contributions to pharmacology are in accord with those exemplified

by Otto Krayer. More information on

Otto Krayer.

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The David Lehr Research Award is intended to extend funding for preclinical or clinical research directed toward improving human health.

This award is made possible by an endowment to ASPET from Mrs. Lisa Lehr in honor of her husband, the late Dr. David Lehr, former chair of the Department of Pharmacology of New York Medical College.

It includes two years of funding at $50,000 per year.

The Robert R. Ruffolo Career Achievement Award in Pharmacology honors the scientific achievements of scientists who are at the height of their careers (typically mid-to late-career) and who have made significant contributions to any area of pharmacology. This award recognizes the contributions made to drug discovery and development by Dr. Ruffolo.

The Reynold Spector Award in Clinical Pharmacology recognizes excellence in research and/or teaching in clinical pharmacology. It was established in recognition of Dr. Spector’s dedication and contributions to clinical pharmacology.

The Pharmacia-ASPET Award in Experimental Therapeutics recognizes and stimulates outstanding research in pharmacology and experimental therapeutics, basic laboratory, or clinical research that has had, or potentially will have, a major impact on the pharmacological treatment of disease.

ASPET Division Sponsored Awards Sponsored by the ASPET Division for Drug Metabolism The ASPET Division for Drug Metabolism Early Career Achievement Award has been established to recognize excellent original research by early career investigators in the area of drug metabolism and disposition. The awardee will deliver a lecture at the ASPET Annual Meeting at EB2017 and will be invited to publish a review article in Drug Metabolism and Disposition.

Sponsored by the ASPET Division for Neuropharmacology The ASPET Division for Neuropharmacology Early Career Independent Investigator Award recognizes and honors a young investigator who is working in any area of Neuropharmacology. The award is open to early career stage investigators from all types of organizations, including academia, industry, private, or government institutes.

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Sponsored by the ASPET Division for Toxicology The ASPET Division for Toxicology will present three awards to recognize outstanding research contributions to toxicology by members at various career stages. The awards include the Career Award, the Junior Investigator Award, and the New Investigator Award.

Sponsored by the ASPET Division for Cardiovascular Pharmacology The Benedict R. Lucchesi Young Scientist Travel Award in Cardiac Pharmacology was established to honor Dr. Lucchesi’s lifelong scientific contributions to our better understanding and appreciation of the pharmacological treatment and prevention of cardiovascular disease and for his mentoring of countless prominent cardiovascular pharmacologists in translational approaches.

The applicant must be within 10 years of receiving their PhD.

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Have you mentored a young investigator whose original research is outstanding?

Nominate them for the Abel Award.

Did your mentor have a profound impact on you and the pharmacology community?

Nominate your mentor for the Axelrod Award.

Do you know someone who epitomizes high standards of ethical behavior, scientific scholarship, publication, and teaching?

Nominate them for the Krayer Award.

Are you an investigator looking for extended funding for research directed toward improving human health?

Nominate yourself for the Lehr Research Award.

Do you know a clinical pharmacologist who excels in research and/or teaching?

Nominate them for the Spector Award.

Is the head of your department or lab at the height of their career, having made significant contributions to an area of pharmacology?

Nominate them for the Ruffolo Award.

Do you have a colleague who has made a major impact on the pharmacological treatment of disease?

Nominate them for the Pharmacia-ASPET Award.

ASPET is grateful for all of our members who helped to fund the scientific achievement awards. In particular, for our 2017 awards, we’d like to thank Mrs. Lisa Lehr, Dr. Reynold and Mrs. Michiko Spector, Dr. Robert Ruffolo, and Dr. Charles Rutledge.

June 2016 • The Pharmacologist

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Taxol:

Barking Up the Right Tree

Reprinted with permission from Florida State University Office of Research. Photo: Ray Stanyard.

Rebecca J. Anderson

The Pharmacologist • June 2016

One morning, Bob Holton discovered that his Tallahassee laboratory had been vandalized. An Iowa football coach had broken in, wanting a drug for his dying mother (1, 2).

Reports of innovative synthetic chemistry rarely interest the general public, but Holton’s recently published paper had attracted considerable media attention. Investigators claimed that the drug suppressed Dr. Robert Holton ovarian and breast cancer better than anything else. And, it was exceedingly hard to get.

Holton was attending a North Carolina high school in 1960 when the National Cancer Institute (NCI) first started testing plant extracts for their potential as anticancer drugs. The NCI had created the Cancer Chemotherapy National Service Center five years earlier as a simple service for assessing small synthetic compounds. The screening program rapidly expanded, testing 30,000 small molecules annually, and then added natural products (3, 4).

In June 1960, the US Department of Agriculture (USDA) began collecting a wide variety of plant specimens for the program (4).

Other NCI contractors then prepared plant extracts, conducted initial screening, and isolated pure compounds from crude extracts that exhibited activity. Over the next twenty years, NCI would evaluate 114,045 extracts from more than 15,000 plant species (2, 4).

85

Barclay’s Bark Among those assigned to do the plant collections was Arthur Barclay, a 30-year-old botanist who had joined the USDA’s research branch after graduating from Harvard (3). Barclay’s first assignment for the NCI program was collecting sunflower and daisy specimens in South Africa. In 1961, he was sent to the southwestern US and Mexico (4).

On June 19, 1962, Barclay arrived in northern California and continued collecting specimens throughout northwest Nevada, Oregon, and Washington. On August 21, he ventured to a spot at the foot of Mt. St. Helens in the Gifford Pinchot National Forest (2, 3). At an elevation of 1,500 feet, Barclay and his three graduate student assistants found a 25-foot Pacific yew tree, Taxus brevifolia (3).

They put twigs, needles, and fruit from the tree in a burlap bag labeled PR-4959 and put bark samples in another bag marked PR-4960—in all, about 15 pounds of material (2, 4).

They then hiked seven miles to their base camp in Packwood, Washington, and spread the material on the floor of an abandoned house that served as their impromptu staging area. After a few days, the dried yew specimens (now less than a third of their wet weight) were packed, labeled, and shipped to the USDA’s research center in Beltsville, Maryland (2).

The USDA sent the yew specimens to the Wisconsin Alumni Research Foundation, one of the labs contracted by the NCI to prepare crude plant extracts (3). To test for anticancer activity, the NCI arranged to have the crude extracts screened in bioassays at several other contract labs (e.g., Arthur D. Little, Hazleton Labs, and Microbiological

Associates). The assays included one in vitro assay (KB cell culture) and a few in vivo assays of leukemia in mice (4).

On May 22, 1964, Microbiological Associates in Bethesda, MD, reported that the PR-4960 bark extract was active in the KB assay (3, 4). The lab confirmed the KB activity in June and July, but the in vivo results were inconsistent (5).

The bark extract was active in L1210 leukemia mice in one experiment but not in another. In other leukemia and lymphoma models, the extract was inactive. Nevertheless, the repeated cytotoxic effect in the KB assay met the NCI’s criteria (5, 6). The next step was determining the compound(s) in the extract responsible for activity. The NCI had contracted several academic chemistry laboratories to fractionate active extracts and isolate pure compounds. But for that, the chemists needed a larger sample of bark.

The USDA dispatched Barclay to the spot where he had collected PR-4960. On September 8, 1964, he bagged 30 pounds of bark from the Pacific yew tree, recording the sample as PR-8059 (3, 4). It was shipped to Monroe Wall at the Research Triangle Institute in North Carolina.

The Fifth Wall Monroe Wall began his career at the USDA in 1940. As a chemist, he was responsible for analyzing plant extracts at the agency’s research branch in Philadelphia (4). Ten years later, his priority shifted to cortisone, a newly discovered “wonder drug” for treating rheumatoid arthritis.

Cortisone was a steroid laboriously extracted from animal adrenal glands, and supplies were limited (3).

Because of the great demand, President Harry Truman directed government researchers to find better ways of producing it.

Mount St. Helens in the Gifford Pinchot National Forest in Washington.

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Reprinted with permission from Florida State University Office of Research. Photo: Ray Stanyard.

The USDA’s Philadelphia branch mounted an intensive effort to find plant steroids that could serve as a starting material for making cortisone synthetically. For nine years, Wall’s team sent promising samples to the National Institutes of Health for evaluation (3). Unfortunately, most of the plant extracts lacked steroid precursors.

Wall sent about 1,000 of his plant extracts to the NCI’s fledgling cancer screening program (3, 4). A sample from Camptotheca acuminata, a large shade tree that is native to China, showed impressive activity (2, 3). However, because the USDA research branch’s mandate was steroid chemistry for cortisone production, extracts with anticancer properties were not pursued (3).

Frustrated by the USDA’s lack of interest in C. acuminata, Wall moved to the Research Triangle Institute in July 1960. Founded just two years earlier, this new research venture linked the university towns of Raleigh, Durham, and Chapel Hill, and for Wall, the move to North Carolina was risky. He had built a stellar 20-year reputation at the USDA and left behind a state-of-the-art lab (2, 3).

Starting with “nothing but four walls,” the fifth Wall created a robust chemistry program and a thriving Natural Products Laboratory (3). He also reestablished his relationship with the NCI (2).

By this time, the NCI’s simple screening service had evolved into a “massive machine,” capable of doing everything for drug development from animal breeding

to clinical trials. The NCI also maintained banks of frozen tumors and the world’s largest database of experimental drugs (4).

Wall joined chemists at a handful of academic laboratories that the NCI had contracted to isolate and purify active compounds from crude plant extracts (2, 4).

Along with his colleague, Mansukh Wani, Wall resumed his work on C. acuminata. They succeeded in isolating camptothecin from a sample of wood and bark, and the NCI subsequently initiated clinical trials (3).

From Trash to Treasure In September 1964, Bob Holton was an undergraduate at the University of North Carolina—just 14 miles from Wall’s laboratory—when Barclay’s PR8509 sample of Pacific yew bark arrived. It was one of seven plant samples in that shipment—all “confirmed actives” in the screening assays and all slated for fractionation and isolation (2, 4).

Wall and Wani were preoccupied with camptothecin, especially making supplies so that the NCI could start clinical trials (3). No one knew much about the Pacific yew, and the variable responses in the mouse assays provided little incentive for Wall to change his priorities (4).

About six months after the yew bark arrived, Wall finally started the tedious process of fractionating the crude extract. In a slow, iterative process, each extract fraction was submitted for in vitro (KB) and in vivo (L1210) assessment at Hazleton Laboratories, one of the NCI’s contractors (3, 4).

By December 1965, Wall had exhausted his supply of yew bark and asked the NCI to arrange another collection. In May 1966, Wall received 45 pounds of bark, 135 pounds of twigs and needles, and 55 pounds of wood from Pacific yews (4).

Wall continued refining the extracts. One fraction was 1,000-fold more potent than the crude extract and gave excellent results in the mouse assays (4). On May 20, 1966, an excited Wall told the NCI, “This is the broadest spectrum of activity we have ever noted in our samples” (2, 4). In what proved to be a prophetic observation, Wall noted that the purified yew fraction was active in an assay that led to the discovery of the first vinca alkaloids. None of Wall’s previous Dr. Monroe Wall and Dr. Mansukh Wani

The Pharmacologist • June 2016

Reprinted with permission from Bugwood.org. Photo: Dave Powell, USDA Forest Service (retired).

87

Pacific yew tree, Taxus brevifolia

plant specimens had shown activity in that particular assay (2, 4).

In September 1966, Wall and Wani succeeded in crystallizing the active compound, which they designated K172 (3, 4). Unfortunately, yew bark contained very little K172. From 12 kg of dried bark, they could extract only 0.5 gram of pure K172, a yield of just 0.004% (4).

In August 1966 and again in March 1967, Wall requested more material. “We need a lot more…if we are going to get enough product even for preliminary chemistry and the necessary preliminary antitumor studies” (4). The USDA arranged for another collection, and 2,500 pounds of yew bark were shipped to Wall’s lab in North Carolina (4).

K172 was a complicated molecule. But even before Wall and Wani elucidated its chemical structure, they knew it contained some hydroxyl groups, making it an alcohol (3). With this in mind and also drawing on the yew’s botanical name, Wall named the compound “taxol” in June 1967. He thought taxol “had a nice ring to it,” and the name stuck (3, 4).

Bob Holton had now moved to Florida State University. His doctoral research centered on the “secondary metabolites” produced by flowering plants in the daffodil family (2). Secondary metabolites do not support a plant’s vital functions or growth.

Rather, they play a defensive role, deterring insects and other predators. Not surprisingly, many of these complex molecules are poisonous, but they have also been explored for medicinal utility. Those with cytotoxic properties were ideal candidates for cancer

treatment. Holton, who was training as a synthetic organic chemist, focused on isolating some of these enormously complicated molecules and then finding a way to make them in the lab (2).

Searching for Taxol Now that taxol had been identified as the anticancer substance in yew extracts, the NCI wanted to know the best source of it. They tested extracts from Taxus baccata (English/European yew), T. cuspidata (Japanese yew), T. floridana (Florida yew), T. canadensis (Canadian yew), T. globosa (Mexican yew), and T. chinensis (Chinese yew). Most specimens contained taxol, but the yield was somewhat lower than from Pacific yews (4).

They also tested samples of Pacific yews collected throughout the Pacific Northwest, from California to Alaska. The KB results varied and could not be easily correlated with the location where the trees grew.

In a further study, many extracts of Pacific yew bark, roots, wood, and needles showed at least some activity. Needle extracts were sometimes more active than bark but other times much less. Overall, the NCI concluded that bark from the Pacific yew consistently yielded the most taxol.

Climbing Everest Wall’s main interest was elucidating the chemical structure of taxol. After years of painstaking analysis, he succeeded. The molecule consisted of a small side chain attached to a large three-ring component called a taxane (7).

June 2016 • The Pharmacologist

88 Wall and Wani published their paper in May 1971, and taxol’s chemical structure captured the imagination of many academic researchers. At Stanford University, Robert Holton was 27 years old and just starting his postdoctoral training. When he read the paper, all he could say was, “Wow” (2). Taxol was the ultimate chemical synthesis challenge—but much too complicated for postdoctoral research. For Holton, taxol would have to wait (2).

Organic chemistry professors were also intrigued.

Laboratory synthesis of taxol would require ingenuity and new approaches to chemical reactions. For them, taxol was “a molecular Mount Everest” (4).

The National Institutes of Health provided some grant money for taxol research. A few professors explored structure-activity relationships, but most were driven by the chemical synthesis challenge (1). None of them viewed taxol as a viable commercial product (4).

Monroe Wall, on the other hand, thought the low yield and complex structure should not pose barriers to taxol development. In the early 1970s, he traveled to Bethesda a dozen times to advocate for taxol (2).

This is the kind of chemical that only a tree would make

Reprinted with permission from PNAS. Insights into the mechanism of microtubule stabilization by taxol. “Copyright (2006) National Academy of Sciences, U.S.A.”

But the NCI decision-makers saw only modest activity in the mouse assays and had other compounds that looked more promising.

As a further handicap, Wall could not devote the time to extract all of the taxol needed for development.

In February 1974, he sent his remaining supply of taxol (815 mg) to the Natural Products Branch of the NCI (4).

The timing was fortuitous. The NCI had begun shifting from its heavy reliance on leukemia animal models. Slow-growing solid tumors caused the majority of cancer deaths in the US, and to represent them, the NCI added the Lewis lung and B16 (melanoma) tumor models to their screening program (4). Wall’s taxol sample was tested in these tumor models in April 1974, September 1974, and June 1975. The results were mixed and kept taxol low on the priority list (4, 5).

In October 1976, Matthew Suffness joined the Plant and Animal Products Section of the NCI’s Natural Products Branch. A pharmaceutical chemist, Suffness was

The Pharmacologist • June 2016

well acquainted with plant chemistry and extract screening. He reviewed the accumulated taxol results—some of it dating back 12 years (2, 4). On the strength of the consistent activity in the KB assay and the more recent B16 tumor assay results, Suffness realized that taxol met the NCI’s criteria for further development—but just barely (5).

On April 18, 1977, the NCI finally decided to move forward with taxol (4, 5). The next hurdle was formulating it for clinical trials, and for that, they needed more taxol. The NCI contracted Polysciences, a small industrial chemical supplier in Warrington, Pennsylvania, to purify taxol using Wall’s methods.

At the end of April 1977, Polysciences received “two drums of tar” (4). The 26 kg lot of concentrated extract came from bark collected in the Pacific Northwest in 1967 and 1968, and it had been sitting in storage. Polysciences successfully isolated 110 grams of pure taxol and delivered it to NCI in March 1978 (4).

Most of it was used for formulation development.

Clinicians needed an intravenous liquid for their patients. Unfortunately, taxol was virtually insoluble (5, 8). After a year of failed attempts, the NCI team found that taxol dissolved in a solution of 50% Cremophor EL and 50% ethanol (5, 9). Cremophor EL (a 35:1 mixture of ethylene oxide and castor oil) had been used to formulate other drugs, such as cyclosporine (2). But when given as a large bolus, Cremophor EL could cause vasodilation, shortness of breath, and hypotension (9).

Dr. Susan B. Horwitz

Horwitz Shakes Things Up In parallel with the formulation studies, the NCI researchers began studying taxol’s mechanism of action. They also invited a few external scientists, including Susan Horwitz, to join the effort (10).

Horwitz was a molecular pharmacologist at Albert Einstein College of Medicine and had been studying the cytotoxic mechanism of action of other natural products, bleomycin in particular.

Although unfamiliar with taxol, she was immediately fascinated. “This is the kind of chemical that only a tree would make” (10). She decided to devote a month to the project, and if nothing interesting happened, she would move on. Horwitz received a 10 mg sample in June 1977. And it was interesting. In cultured HeLa cells, taxol potently inhibited cell division (10). She requested another sample in October (4).

Cell division—and other cell functions—require a dynamic equilibrium between microtubules and monomeric tubulins. Any compound that disrupts this equilibrium is likely to be cytotoxic (1, 5, 9).

Several anticancer compounds, including colchicine and the vinca alkaloids, inhibited cell division by binding to tubulin and preventing formation of microtubules. By the 1960s, colchicine had become an indispensable tool to cell biologists, who used it to study cell division.

To Horwitz’s surprise, taxol disrupted cell division differently. Instead of inhibiting microtubule formation like the other antimitotic compounds, taxol shifted the equilibrium in favor of microtubule formation and inhibited their disassembly (10). The accumulated mishmash of microtubules prevented cancer cells from coordinating cell division. The cells soon collapsed and died (2, 3, 9).

Horwitz published her findings in 1979 (10). Cell biologists worldwide immediately recognized the value of taxol for studying cell dynamics.

Taxol’s novel mechanism of action complemented depolymerizing agents like colchicine, and the NCI was flooded with requests for samples of it (4).

The French Connection Horwitz’s paper also sparked the interest of Pierre Potier in France. Potier had been investigating natural products and synthetic compounds that acted like colchicine (6). His group assessed those compounds in a sensitive in vitro assay that measured interference with the tubulin assembly-disassembly process (6).

Potier worked at a facility near Paris, the Centre National de la Recherche Scientifique, which was located on a campus full of Taxus baccata (European yew).

Coincidently, some of those trees had been Dr. Pierre Potier felled to make way for a new road across the campus (6). Potier took advantage of this opportunity to assess the needles, roots, bark, and wood of the European yew for taxol-like activity.

The lab prepared extracts and tested each fraction in the tubulin assay (6). The most abundant active constituent in the needle extracts was 10-deacetylbaccatin III (10-DAB). Potier recognized this molecule as the large taxane ring portion of taxol.

Interestingly, 10-DAB had not been active in the NCI’s screening assays, but Potier’s tubulin assay was more sensitive and detected mild inhibition of microtubule disassembly (6).

Potier’s group published their findings in 1981.

Chemists immediately realized 10-DAB was an ideal starting material for synthesizing taxol (3). Unlike bark, yew needles were a renewable resource, and 10-DAB was easy to obtain. A number of top-notch chemists were awarded NCI grants to find a practical way of adding the small side chain to the C13 site of 10-DAB, which would produce taxol (2, 3).

In France, Potier also pursued taxol synthesis through two collaborations. The first was with Andrew Greene, who headed Centre National’s research group in Grenoble. Greene’s group would synthesize the taxol side chain. Potier’s group in Paris would devise a synthetic route for attaching the side chain to 10-DAB (4).

Potier’s natural products group also signed a collaborative agreement with Rhône-Poulenc Rorer. Together, they would explore the chemistry of taxane compounds, define the structure-activity relationships, and seek new and patentable anticancer compounds (4).

All of these chemists knew attaching the side chain to 10-DAB was easier said than done. The 15-membered taxane ring system of 10-DAB had many points where the side chain preferred to attach, rather than the C13 site that would create taxol (9). Progress was slow.

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Reprinted with permission from ICSN/CNRS.

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Using Yews Toxicology testing of taxol began in October 1980, and to keep development on track, the NCI needed more of it (4). Without a viable synthetic method, the most expedient source remained natural extraction.

And the best extracts, based on the NCI’s assessment, came from Pacific yew bark.

Taxus brevifolia is an evergreen with reddishpurple bark and flat, inch-long needles (3). Yew trees grow very slowly, reaching a height of about 30 feet in 100 years. Yew wood is hard, heavy, and slow to rot (3). The English yew provided wood for longbows that were critical to the English victories at Crecy and Agincourt, and Wordsworth extolled its virtues in his poem, “Yew Trees” (5). But Pacific yew wood was not of much commercial use except for fence posts (3, 4).

Pacific yews grow in the shade of giant conifers, on the banks of streams, in deep gorges, and in damp ravines, but they are widely scattered. According to one Forest Service researcher, “If you walk over 100 acres of forest, you can expect to find yews on four of them” (8).

Young yews are little more than shrubs—too small to harvest any bark from (8). Adding to the difficulties, bark could only be collected during the spring and summer months when the sap was running (4). The paper-thin bark was laboriously hand-peeled, either from the standing trees or after they were felled.

Either way, stripping the bark killed the tree (1, 3).

In October 1981, collectors delivered 3,366 lbs of bark to Polysciences. Over the next year, Polysciences produced about 260 g of pure taxol to support the toxicology studies (4, 5).

Shifting to the Clinic In the late 1970s, the NCI expanded its repertoire of solid tumor screening assays. Colonies of immunosuppressed mice were implanted with human tumors from the colon (CX-1), lung (LX-1), or breast (MX-1)—animal models that represented the three major types of cancer in the US. Taxol inhibited tumor growth in the colon and lung assays. Even better, taxol produced considerable regression of the breast tumors (4).

Phase I clinical trials began in April 1984 at seven clinical sites involving 101 patients (4, 5). Like virtually every other stage of taxol’s development, things got off to a rocky start. Drug injections caused hypersensitivity reactions in about 10% of the patients. The problem was attributed to the Cremophor-ethanol vehicle (5, 9).

The Pharmacologist • June 2016

Pretreatment with antihistamines and dexamethasone and a slow, continuous 24-hour infusion minimized the hypersensitivity responses (1, 5, 9).

Some of the patients with ovarian and renal cell carcinoma responded to taxol treatment, and on April 16, 1985, the NCI decided to move forward with Phase II trials (4, 5). Those trials required considerably more taxol. Having ended its interagency agreement with the USDA, the NCI made arrangements directly with an Oregon fencepost dealer to collect 12,000 lbs of yew bark. Concerns of wildfires delayed collection, but 11,000 lbs of bark were delivered in the fall of 1986 (4).

The Phase II trials were conducted at the same seven centers that had participated in the Phase I trials. The Johns Hopkins Oncology Center recruited ovarian cancer patients, and the Albert Einstein College of Medicine recruited renal cancer patients.

Encouraged by taxol’s response in the B16 (melanoma) mouse assay, the remaining five centers (which were part of the Eastern Cooperative Oncology Group – ECOG) recruited melanoma patients (4).

Because taxol had shown impressive activity in the MX-1 mammary tumor screen, the NCI wanted to recruit breast cancer patients, too. But those trials were delayed. Lack of taxol supplies had become critical (1).

On December 1, 1986, the NCI’s Developmental Chemotherapy Section met to address the crisis. So far, three of the Phase II centers had enrolled patients.

Only one of the 14 melanoma patients at the ECOG centers had responded to taxol. At Johns Hopkins, the results were more encouraging. Two of the first seven patients with refractory ovarian cancer had shown a partial response, and one had a marginal response (4).

The NCI had sufficient taxol to supply the enrolled patients, but there was not enough on hand to start even one more Phase II trial. And, the next delivery from Polysciences was not expected before spring.

At least seven planned Phase II trials were put on hold. ECOG stopped enrollment in February 1987, with 3 of 24 melanoma patients showing partial responses (4). Johns Hopkins continued to enroll ovarian cancer patients (1).

To ease the crisis, the NCI ordered 60,000 lbs of bark, which would yield about 3 kg of taxol. Patrick Connolly, a lumber contractor, collected 37,000 lbs of bark in the 1987 harvest season and delivered the remainder of the bark in August 1988 (4).

Extracting and purifying that much material stretched the capacity at Polysciences to the limit.

91 The NCI contracted Hauser Chemical Research, a natural products facility in Boulder, Colorado, to assist (4). In February 1989, Hauser completed the crude extraction from 25,000 lbs of Connolly’s collection.

Polysciences and Hauser then began isolating pure taxol from the extract.

The 3 kg of taxol produced from Connolly’s bark harvest was sufficient to resume the suspended Phase II clinical trials. But to continue beyond that, NCI realized that they needed even more taxol.

In April 1989, NCI awarded a contract for another 60,000 lbs of bark to John Destito at Advanced Molecular Technologies in Bellevue, Washington.

Destito was a capable, creative, and collaborative entrepreneur. But despite his best efforts, he experienced frustrating delays.

To speed things up, Destito decided to stockpile the yew logs through the winter and peel the bark mechanically after steaming the cut logs at 40°C. Destito’s ingenious method allowed harvesting out of season, automated the debarking process, and produced the same taxol yield as hand-peeling (4).

Going Commercial The clinical results, especially from Johns Hopkins, kept getting better. William McGuire, who led the Johns Hopkins clinical trial, reported his results to the American Society of Clinical Oncology in May 1988.

Noting a 30% response rate, he said, “There is no other drug that has produced this kind of response in drug refractory ovarian cancer…There were patients treated who were two to three weeks from death who are still alive today because of taxol” (4, 11).

At the NCI, one official told a colleague The cost of that public interest was converting Pacific intense. “People are yew bark to taxol begging for it” (4). But the cost of converting Pacific was draining the yew bark to taxol was NCI’s budget draining the NCI’s budget, and many other promising drug candidates were competing for the same funds (2). The NCI wanted to develop taxol but needed help.

The solution was a CRADA. Congress had recently instituted Cooperative Research and Development Agreements under the Federal Technology Transfer Act. CRADAs encouraged and facilitated the transfer of commercially promising knowledge from federal agencies to private industry.

On August 1, 1989, the Federal Register published the NCI’s announcement for the taxol CRADA. To qualify, a drug company needed to have experience developing natural products and be willing to cover the cost of collecting bark, as well as extracting, purifying, and formulating taxol. The NCI would turn over all of its taxol data to the company, and in return, the company was expected to expedite taxol’s development and regulatory approval (1).

Semi-synthesis Succeeds Working independently and largely ignored by the NCI, Pierre Potier and Andrew Greene had continued their efforts to synthesize taxol. In 1988, after nearly a decade of research, they published their “highly efficient practical approach” for attaching 10-DAB to the appropriate side chain (12). They also applied for a French patent.

In the wake of the Potier-Greene paper, the NCI greatly increased funding for taxol chemistry projects.

Purifying taxol from bark took more than a year, and the NCI realized that demand was accelerating much faster than yew trees grew. Soon, 30 chemistry groups were working on the synthesis of taxol (1).

Robert Holton was now a chemistry professor at Florida State University. Academic tenure afforded him more freedom in selecting research projects. He chose taxol. But despite the publicity surrounding the clinical supply crisis and Potier-Greene’s semisynthetic achievement, Holton’s interests were purely academic. He was driven by the intellectual challenge of synthesizing taxol from scratch (2).

Holton had already succeeded in synthesizing part of the taxane ring when Matthew Suffness called him. Suffness, who had trained in the same Stanford lab as Holton, was now Chief of the Natural Products Branch at the NCI (2). He assured Holton that taxol was not just a chemical curiosity. Thousands of patients needed the drug, and “somebody’s gotta figure out how to make it” (2). Holton put aside his total synthesis project and focused on practical solutions.

Within 18 months, Holton found a semi-synthetic route that delivered twice the yield of Potier’s process (2, 4). Holton patented his method in May 1991 and began contacting drug companies that might be interested in adapting it for commercial production of taxol (1, 2). One of them was Bristol-Myers Squibb.

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The Owl in the Tree Concerns were intensifying that taxol extraction from Pacific yew bark was unsustainable. Since the 1940s, the logging industry had been given fairly free rein to clear-cut old-growth forests and harvest commercially valuable species such as Douglas fir, Sitka pine, and western cedar. Loggers gathered the remaining “trash trees,” shrubs, and plants into “slash piles” and burned them (4). The cleared area was then replanted with an even-age forest containing only commercially valued trees.

Aggressive logging had destroyed about 85% of the old-growth forests in the Pacific Northwest, including “trash trees” like the Pacific yew (4). To preserve a portion of the old-growth forests, environmentalists succeeded in listing the spotted owl as a threatened species in June 1990. Unfortunately, the spotted owl was a poorly chosen surrogate for the plants and animals in this habitat. It wasn’t cuddly like baby seals, and the poor spotted owl was caught in a highly politicized battle between environmentalists and workers whose livelihood depended on logging.

Everyone was now hugging the scrawny tree Because yews had been commercially unimportant, no one had bothered to conduct a proper inventory, and estimates varied widely. Regardless, sooner or later the species would be extinct, and everyone was now hugging the scrawny tree. It was the sole source of a potent drug that could help thousands of cancer patients.

In an extraordinary move, both sides came together to support the Pacific Yew Act. Pacific yew trees were declared a public resource, and the Secretaries of Agriculture and Interior were charged with managing all yew trees on federal lands. Pacific yews could be felled only to manufacture taxol (4).

Accelerating Approval After more than a year of negotiations, the NCI and Bristol-Myers Squibb signed the taxol CRADA in

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January 1991—the latest step in a long-standing and special relationship (4). In 1972, Bristol-Myers had been the first drug company to sign an agreement to market drugs emerging from the NCI’s cancer screening program. Furthermore, Bristol-Myers Squibb was one of the few drug companies with broad experience developing cancer drugs and handling natural products (13).

Under the CRADA, Bristol-Myers Squibb took over the NCI’s contracts for all Pacific yew collections of bark, needles, and twigs (1, 9). In addition, the Pacific Yew Act effectively reserved all Pacific yew trees on federal lands for Bristol-Myers Squibb and only for medicinal use until 1998 (4).

To satisfy the environmentalists, Bristol-Myers Squibb paid for research on yew ecology, the first official inventory of Pacific yew trees, and an Environmental Impact Statement assessing the effect of short-term, large-scale bark harvesting (13). BristolMyers Squibb also contracted Weyerhaeuser, the largest supplier of timber in the US, to cultivate Taxus trees and conducted research to optimize their growth and other properties (1, 13-15).

When John Destito’s NCI contract expired, BristolMyers Squibb contracted Hauser Chemical Research in Colorado as its supplier of both yew bark and pure taxol (2, 13). Hauser collected 80,000 lbs of bark in 1990, 1.6 million lbs in 1991, and another 1.6 million lbs in 1992 (1, 13, 16). Hauser’s process improvements doubled the yield of taxol, producing about 230 kg from 1990-1992 (4).

Bristol-Myers Squibb formulated taxol (30 mg/vial) free of charge for the NCI’s clinical programs (1, 13).

In 1991, the company supplied about 3,750 vials per month, enough to treat 500 patients (1, 14).

In 1992, the company increased supplies from 5,000 to 50,000 vials per month (13, 14). This permitted the NCI to establish an ovarian cancer treatment referral program, as well as a referral protocol to treat breast cancer patients (13).

A mere 18 months after signing the CRADA, BristolMyers Squibb submitted the accumulated taxol data to the Food and Drug Administration. Taxol worked in patients who had become resistant to platinum-based therapy, which was the current “best drug” for ovarian cancer, and it was effective in patients who had been heavily pretreated with radiation and chemotherapy— factors that usually reduced responses to subsequent therapy (9, 11).

Reprinted with permission from Florida State University Office of Research. Photo: Ray Stanyard.

93 On December 29, 1992, FDA approved taxol to treat refractory ovarian cancer, making it the first and only approved drug to emerge from NCI’s plant screening program (3, 17).

Taxol by Any Other Name To further protect its investment, Bristol-Myers Squibb secured a trademark for its new product. In a rather controversial move, the US Patent and Trademark Office granted the company’s request to register Taxol on May 26, 1992 (4).

At this point, taxol had been in widespread use as a generic name for more than 20 years. Also, going unnoticed was a laxative product that Continental Laboratories had trademarked and sold as taxol in the early 20th century (5).

Regardless, Bristol-Myers Squibb now had exclusive rights to call its anticancer drug Taxol. Within a couple of years, Taxol had been registered in more than 50 countries (2). In 1993, the USAN authorized “paclitaxel” as the new generic name of the molecule that had formerly been called taxol.

Yew Turn While optimizing extraction procedures, BristolMyers Squibb was working equally hard to reduce, if not eliminate, its dependence on Pacific yew bark (14). The long-term solution to the supply problem was making taxol semi-synthetically, and the company was receptive to Robert Holton’s offer (13).

On April 1, 1990, Bristol-Myers Squibb signed an exclusive licensing agreement with Florida State University to use Holton’s taxol patents, including an improved method that gave an 80% overall yield in just four steps (2). In exchange, Florida State would receive royalties on the revenues derived from Holton’s patents.

Bristol-Myers Squibb made speedy progress in scaling up Taxol production at its plant in Ireland, using Holton’s improved method and 10-DAB obtained from Indena, a natural products company in Milan, Italy (2, 8, 13, 16). Indena extracted large quantities of 10-DAB from renewable biomass (needles and twigs) of European (Taxus baccata) and Himalayan (Taxus wallichiana) yews (13, 15).

Bristol-Myers Squibb needed regulatory approval to change Taxol manufacturing from bark extraction to the new semi-synthetic process (13). The FDA approved the change on October 14, 1994, making further bark collections unnecessary (17).

The Bristol-Myers Squibb contract with Hauser was not renewed, and with that, the Pacific yew crisis ended. Environmentalists rejoiced and federal conservation officials were relieved (15). The little yew tree had gone from trash to treasure to trivial (2).

A Quantum Leap Abundant Taxol supplies hastened the pace of clinical trials for other cancers. The first reports of efficacy in refractory advanced breast cancer came from the MD Anderson Cancer Center in October 1990 (1). The response rate of 56% was even better than in ovarian cancer (18). A trial at Memorial SloanKettering in 1992 confirmed the results (19). Taxol was effective even in patients who had become resistant to anthracycline-based therapy, the current “best drug” for breast cancer (9). The FDA approved Taxol for refractory breast cancer in April 1994 and for non-small cell lung cancer in June 1998 (17).

When Taxol made its debut in January 1993, it was hailed as the most important anti-cancer drug in 15 years, but it was not perfect (2, 8). As with other chemotherapy agents, bone marrow suppression and white blood cell depletion were common. Taxol also caused neuropathy, typically in the hands and feet, and cardiac disturbances (9).

Nevertheless, Taxol was the best thing The little yew tree clinicians could offer at had gone from trash the time (2). In 1995, to treasure to trivial it was the best-selling cancer drug in the world with more than $500 million in sales. In 2000, sales reached nearly $1.6 billion (2).

Totally Synthesized Chemists were still lured to the challenge of synthesizing Taxol from scratch . As Robert Holton explained to a reporter, “The ring systems are unexplored ground. The stereochemistry, the variety of substituents, the conformational peculiarities, the strange reactivity…it’s an incredible challenge” (1). More than 100 academic groups worldwide were working on it (1, 2).

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94 Then, in a virtual photo finish, two groups succeeded (2, 4). On February 17, 1994, Kyriacos Nicolaou and his team at the Scripps Research Institute reported their success (20). Within a week, Holton’s group at Florida State University published their work (21).

Total synthesis of Taxol was a major intellectual achievement, but it was of little practical importance.

Nicolaou’s method involved 28 steps (9). Holton’s synthesis required 40 steps, and the yield was an abysmal 2% (2, 4).

Enter Taxotere

Reprinted with permission from Virginia Tech. Photo: David G.I. Kingston.

While Taxol made headlines in the US, Potier, Greene, and their colleagues in France continued to improve their own semi-synthetic method. In collaboration with Rhône-Poulenc Rorer, they also studied the structure-activity relationships of about 40 intermediates and analogs (1).

Among those compounds was RP56976, which was slightly more active than Taxol in the tubulin assay.

RP56976 also exhibited significant antitumor activity

(6). Most impressively, it was 25% more soluble and had better bioavailability than Taxol (1, 6, 9). RP56976 was named Taxotere (generic name, docetaxel).

In 1990, Rhône-Poulenc Rorer began Phase I clinical trials in Europe and the US under a research and development agreement with the NCI (1, 9). Referring to their own semi-synthetic method, Potier boasted, “Our group has solved the problem of industrial production…We are today producing very large amounts of Taxotere” (1).

The FDA approved Taxotere for advanced breast cancer treatment in 1995 (4). It was subsequently approved alone or in combination with other agents for non-small cell lung cancer, prostate cancer, and head and neck cancer (1, 14, 17).

University Royalty Traditionally, American universities aggressively insulated their research from all commercial influences. But the tech-transfer deal between Florida State University and Bristol-Myers Squib caught the attention of many university administrators (2). In 1996, Florida State received more than $28 million in Taxol royalties, and by the end of the decade, the royalties topped $200 million. It was one of the largest patent pay-outs for a single university in history (2).

Florida State used the royalties to underwrite a dozen endowed professorships. Also, under its policy, the university awarded faculty inventors 40% of the royalties arising from their patents, making Holton a very wealthy man (2).

The royalties fundamentally changed Holton’s perspective. His achievements were widely publicized, and hundreds of cancer patients and their loved ones contacted him. He shifted his academic chemistry pursuits and invested his royalties in applied research. He wanted to find a better Taxol analog. “If you have the opportunity to do something that could save someone’s life, you just have to do it” (2).

References 1. Borman

S (September 2, 1991) Scientists mobilize to increase supply of anticancer drug taxol. Chem Eng News 69(35): 11-18.

2. Stephenson

F (Fall 2002) A tale of taxol. Research in Review, Florida State University; available from: http://www.rinr.fsu.edu/ fall2002/taxol.html.

Chemical structures of paclitaxel (Taxol™), docetaxel (Taxotere™) and 10-deacetylbaccatin III (precursor).

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3. Ginsberg

J (April 23, 2003) A National Historic Chemical Landmark: The Discovery of Camptothecin and Taxol®. Science that Matters, American Chemical Society; available from: http:// www.acs.org/content/acs/en/education/whatischemistry/ landmarks/camptothecintaxol.html.

95 4. Goodman J and Walsh V (2001) The Story of taxol: Nature and Politics in the Pursuit of an Anti-Cancer Drug, Cambridge University Press, Cambridge.

5. Kingston DGI (2007) The shape of things to come: structural and synthetic studies of taxol and related compounds. Phytochem 68(14): 1844-1854.

Biosketch:

6. Guénard D, Guéritte-Voegelein F, and Potier P (1993) Taxol and Taxotere: discovery, chemistry, and structure-activity relationships. Acc Chem Res 26: 160-167.

7. Wani MC, Taylor HL, Wall ME, Coggon P, and McPhail AT (1971) Plant antitumor agents.

VI. Isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. J Am Chem Soc 93(9): 2325-2327.

8. Kolata G (May 13, 1991) Tree yields a cancer treatment, but ecological cost may be high.

New York Times; available from: http://www.nytimes.com/1991/05/13/us/tree-yields-a-cancertreatment-but-ecological-cost-may-be-high.html.

9. Joel SP (March 7, 1994) Taxol and Taxotere: from yew tree to tumor cell. Chemistry & Industry, pp. 172-175.

10. Schiff PB, Fant J, and Horwitz SB (1979) Promotion of microtubule assembly in vitro by taxol.

Nature 227: 665-667.

11. McGuire WP, Rowinsky EK, Rosenshein NB, Grumbine FC, Ettinger DS, Armstrong DK, and Donehower RC (1989) Taxol: A unique antineoplastic agent with significant activity in advanced ovarian epithelial neoplasms. Ann Intern Med 111: 273-279.

12. Denis JN, Greene AE, Guenard D, Gueritte-Voegelein F, Mangatal L, and Potier P (1988) Highly efficient, practical approach to natural taxol. J Am Chem Soc 110(17): 5917-5919.

13. DeFuria MD and Horovitz Z (1993) Taxol commercial supply strategy. J Natl Cancer Inst Monogr 15: 195-198.

14. Pink Sheet (March 9, 1992) Bristol-Myers Squibb plans taxol NDA filing by “mid-1992”: 1993 approval possible: supply to NCI will cover all 12,500 refractory cancer patients; available from: https://www.pharmamedtechbi.com/publications/the-pink-sheet/54/010/bristolmyerssquibb-plans-taxol-nda-filing-by-mid1992-1993-approval-possible-supply-to-nci-will.

15. Barnard J (March 13, 1994) Old-growth yew spared as cancer drug source: health: drug firm decides it can’t risk millions producing medication that comes only from slow-growing wild trees. Los Angeles Times; available from: http://articles.latimes.com/1994-03-13/local/me33404_1_national-cancer-institute.

16. New York Times (January 30, 1993) New source of cancer drug spares yew tree; available from: http://www.nytimes.com/1993/01/31/us/new-source-of-cancer-drug-spares-yew-tree. html.

17. New York Times (December 12, 1994) New version of taxol is approved by FDA; available from: http://www.nytimes.com/1994/12/13/science/new-version-of-taxol-is-approved-by-fda. html.

18. Holmes FA, Walters RS, Theriault RL, Forman AD, Newton LK, Raber MN, Buzdar AU, Frye DK, and Hortobagyi GN (1991) Phase II trial of taxol, an active drug in the treatment of metastatic breast cancer. J Natl Cancer Inst 83(24): 1797-1805.

19. Reichman BS, Seidman AD, Crown JPA, Heelan R, Hakes TB, Lebwohl DE, Gilewski TA, Surbone A, Currie V, Hudis CA et al. (1993) Paclitaxel and recombinant human granulocyte colony-stimulating factor as initial chemotherapy for metastatic breast cancer. J Clin Oncol 11(10): 1943-1951.

Rebecca J. Anderson holds a bachelor’s in chemistry from Coe College and earned her doctorate in pharmacology from Georgetown University. She has 25 years of experience in pharmaceutical research and development and now works as a technical writer.

Her most recent book is Nevirapine and the Quest to End Pediatric AIDS. Email

rebeccanderson@msn.com.

In the next issue of The Pharmacologist…

Dr. Anderson will share the story of chlorpromazine and the dawn of psychopharmacology.

Don’t miss the September 2016 issue.

20. Nicolaou KC, Yang Z, Liu JJ, Ueno H, Nantermet PG, Guy RK, Claiborne CF, Renaud J, Couladouros EA, Paulvannan K et al. (1994) Total synthesis of taxol. Nature 367: 630-634.

21. Holton RA, Kim HB, Somoza C, Liang F, Biediger RJ, Boatman PD, Shindo M, Smith CC, and Kim S (1994) First total synthesis of taxol. 2. Completion of the C and D rings. J Am Chem Soc 116(4): 1599-1600.

ASPET recognizes that Taxol is a registered trademark of Bristol-Myers Squibb and that Taxotere is a registered trademark of Sanofi.

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Meeting News Submitted by Michael Wood, PhD

ASPET and ADDC Meet to Review Progress in Academic Drug Discovery Even by casual observation, it seems clear that the licensing of drug candidates is becoming more important to the pharmaceutical industry. In fact, analysts estimate that the proportion of major pharma pipeline candidates originating from outside currently exceeds 50% and predictions suggest that this share will continue to increase. Amid this ongoing industry transformation, a traditional partner is building prominence in a nontraditional capacity.

The role for academia in drug discovery is expanding.

In recognition of this trend, the Academic Drug Discovery Consortium (ADDC) was established in 2012. ASPET connected with the ADDC to co-organize and convene a colloquium on the topic of academic drug discovery directly following the ASPET Annual Meeting at Experimental Biology 2016 in San Diego.

The program was funded by fifteen commercial sponsors, underscoring the interest of both pharma/ biotech and contract research organizations in academic drug discovery.

The colloquium kicked off on the afternoon of April 6 with a partnering event in which leaders of academic discovery centers met with both pharmaceutical search and evaluation experts and representatives from contract research service providers resulting in over 200 interactions. One attendee, Dr. Richard Neubig, professor and chair of the Department of Pharmacology and Toxicology at Michigan State University, commented that “the partnering meetings provided a good mix of potential collaboration/licensing partners and vendors with useful resources for drug discovery applications.” The contacts made during the partnering session expanded the networks of the participants and will undoubtedly catalyze future discussions on collaboration. Given the complexity and the scope of drug discovery, partnership is essential to success and the rapid-fire partnering session of the colloquium was an efficient means to quickly expand networks.

The scientific program of the colloquium launched the following morning with a series of presentations focused on academic drug discovery success stories. The audience heard from established academic discovery centers and newcomers as well.

The individual partnering meetings were held the day before the scientific program Speakers highlighted academic of the Drug Discovery Colloquium.

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studies that sparked key insights into biomedical challenges. They explained how those insights matured into programs that then moved through stages of the drug discovery value chain, and how some had been licensed by commercial enterprises that were either start-ups or established biotech/pharm companies. Dr. John Lazo, professor of pharmacology at the University of Virginia, pointed out that “drug discovery is really at the foundation of ASPET” and described the success stories as templates for “how academics can participate in what is considered commercial territory.” Three of the eight program presentations were selected from ASPET member submissions: Dr. Rangan The Drug Discovery Colloquium was titled “Drug Discovery in America: Recent Successes and Emerging Opportunities.”

Maitra of RTI International – Discovery and Characterization of Apelin Receptor Ligands investments to improve global health. His presentation as Therapeutics for Metabolic Syndrome, served as a reminder that non-governmental Dr. Joseph M. Salvino of Drexel University College organizations can stimulate research into treatments of Medicine – Cx3cr1 Chemokine Antagonists Halt for underserved populations. Reviews of the Structural Metastatic Spreading In Animal Models of Metastasis, Genomics Consortium and the Tau Consortium were and Dr. Matthew Duvernay of Vanderbilt University followed by introductions to the National Cancer – Towards an Efficacious, in vivo Protease Activated Institute Experimental Therapeutics (NExt) and the Receptor 4 Antagonist. The collection of success National Institutes of Health (NIH) Blueprint programs. stories was diverse in both approach and content.

It is worth noting that both programs were specifically However, there were several unifying themes. designed to foster academic Common threads among drug discovery. A panel the presentations were The partnering meetings provided the use of team-based a good mix of potential collaboration/ discussion on partnering drug discovery programs approaches, examples licensing partners and vendors with concluded the speaking of creative solutions to portion of the colloquium, useful resources for drug discovery obstacles and what Dr. and a combined poster/ Lazo labeled as “examples applications buffet rounded out a full day of how failure can lead of programming. Despite to success.” The role the ambitious meeting agenda, attendees entered of academic drug discovery is expanding and this segment of the colloquium provided a means to pause the poster session with indomitable enthusiasm and continued a dialogue on the future trajectory of and review the recent collective experience. academic drug discovery. There can be little question The next stage of the colloquium focused on that the excitement reverberating throughout the assessing some of the resources available to academic drug discovery colloquium will continue to academics with an interest in drug discovery. Dr. echo. It also seems likely that the theme should be Mike Poole, director of the Global Health Office of revisited again in the near future. the President at the Bill & Melinda Gates Foundation, began by revealing how the foundation prioritizes

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ASPET-JPS Lecture at the 89th Annual Meeting of the Japanese Pharmacological Society Submitted by P. Jeffrey Conn, PhD

The beautiful port city of Yokohama, Japan provided the setting for the 89th Annual Meeting of the Japanese Pharmacological Society (JPS), held March 9 - 11, 2016. The Pacifico Yokohama Conference Center, located in the modern Minato Mirai district, served as the meeting venue.

Established in the mid-1800s, the relatively young city of Yokohama has become the second largest city in the ancient country of Japan, combining stunning modern architecture with breathtaking ocean views.

The skyscrapers and elevated moving sidewalks of this futuristic city by the sea were an appropriate backdrop as over 2,000 scientists gathered to hear presentations and participate in discussions regarding the latest research in a broad range of areas of modern pharmacology and biomedical research. The meeting’s theme, “Voyage Beyond the Horizon,” was chosen, in the words of meeting president and organizer, Dr. Kunio Ishii, “in order to

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show that our only path to opening up a bright future for pharmacology lies in taking on bold challenges in unknown fields.” This is a highly appropriate theme at a time when there is a renewed focus in biomedical sciences on translational research and integrating our understanding from an atomic and molecular level to highly complex systems and ultimately human health and disease. As an inherently integrative discipline that spans molecular, cellular, and systems research, pharmacology plays a central role in bridging discoveries across these multiple levels.

Indeed, the evolution of pharmacology as a discipline combined with an increase in collaboration among scientists around the world has created more potential for positive impact than at any time in history. Dr. Ishii’s vision for the JPS meeting correlates perfectly with ASPET’s current emphasis on partnering with other pharmacological societies to facilitate the sharing of information and to encourage collaborative efforts that will lead to new discoveries and advances in treatment for citizens in every country and at every level of society. Consistent with this effort, ASPET has partnered with the British Pharmacological Society (BPS), the Chinese

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Pharmacological Society (CNPHARS), and the JPS. Components of the partnerships include invited lectures, sponsored symposia, and opportunities for cultural and scientific exchange.

It was my honor to present the ASPET-JPS lecture at the 89th Annual Meeting of the JPS. Speaking on the topic “Allosteric modulators of GPCRs as a novel approach to treatment of CNS disorders,” I shared a vision for appropriate and critical roles of academic drug discovery efforts in helping to bring about the next generation of medicines for human diseases that are not effectively treated with current therapeutic agents. As an example, I focused on breakthroughs in discovery and optimization of novel, highly selective positive allosteric modulators of individual subtypes of muscarinic acetylcholine receptors and advancing these novel compounds into development for treatment of devastating brain disorders. These successes highlight the need for intense efforts in every major area included in the overarching discipline of pharmacology, including medicinal chemistry, molecular modeling, cellular and systems physiology, drug metabolism and pharmacokinetics, behavioral pharmacology, and advanced in vivo imaging of drug action in identified brain circuits.

There could be no more fitting place for presentation of these new advances than at the JPS meeting. The studies outlined in this talk trace their roots back to the discovery and use of acetylcholinesterase (AChE) inhibitors for treatment of Alzheimer’s disease. Donepezil (brand name Aricept), the gold-standard acetylcholinesterase inhibitor, was

discovered and developed by Dr. Hachiro Sugimoto and his coworkers in the Japanese laboratories of Eisai Co Ltd., and represents just one of many examples of the strong tradition of pharmacology and drug discovery in Japan.

The ASPET-JPS lecture was only one of many talks and sessions at the JPS meeting highlighting the excellence in pharmacology in Japan and the importance of international collaboration in advancing our discipline. There was no greater example than the work of Dr. Satoshi Ōmura, who gave the plenary lecture. Dr. Ōmura shared the 2015 Nobel Prize in Physiology and Medicine with Dr. William C. Campbell (USA) for their collaboration leading to the discovery of avermectins/ivermectin through a collaborative research program with Merck & Co., Inc. Ivermectin is a ground breaking antiparasitic medicine that has had a tremendous impact in providing an effective treatment for river blindness and elephantiasis. Read more about Ivermectin in ASPET’s March 2016 issue of The Pharmacologist: http://bit.ly/1piu9fm Continuing with Japan’s rich history in pharmacology, Kyoto, Japan, will be the setting for the IUPHAR 18th World Congress of Basic and Clinical Pharmacology, July 1-6, 2018. This meeting will be hosted by the JPS and the Japanese Society of Clinical Pharmacology and Therapeutics and is being organized under the leadership of Dr. Masamitsu Iino, who serves as president of the JPS. Details of the upcoming IUPHAR Congress can be found at www.wcp2018.org/.

The Minato Mirai district in Yokohama with views of the congress venue.

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Pharmacology 2016 with Guest Societies: ASPET, ASCPT, CNPHARS ASPET is pleased to be a guest society at the British Pharmacological Society’s (BPS) annual meeting, Pharmacology 2016, taking place December 13 – 15, 2016.

This will be an international event with two other guest societies, the American Society for Clinical Pharmacology and Therapeutics and the Chinese Pharmacological Society.

We will be holding a joint symposium with the BPS entitled, The Long Reach of the Bowel: Translating Microbiome Science into Therapeutics for Systemic Human Diseases, chaired by ASPET members Pamela J. Hornby, PhD from Janssen and Ross Corriden, PhD from the University of California, San Diego.

Abstract submission and registration will be opening in June 2016. Please check the BPS website for more details: http://bit.ly/1ryonqB.

ASPET will be offering travel awards on a competitive basis to members interested in attending Pharmacology 2016. Undergraduate students, graduate students, and postdoctoral scientists are encouraged to apply. Visit https://www.aspet.org/ ASPET_Travel_Awards/ for more information.

Council Approves Proposal from the BIG IDEAS II Initiative The ASPET council has approved the funding of a BIG IDEAS II Initiative proposal entitled Surmounting the Insurmountable – Obstacles in Drug Discovery and Development: Real-World Case Studies submitted by Drs. Kan He, Paul F. Hollenberg, Michael Holinstat, A. David Rodrigues, Hequn Yin, W. Griffiths Humphreys, Thomas F. Woolf, Emily E. Scott, Wen Chyi Shyu, and Darrell R. Abernethy. The leaders of this BIG IDEAS project will organize a session at the ASPET Annual Meeting at EB2017 to provide a forum for pharmacological experts to discuss “real world” stories recounting when, in their own experience, insurmountable problems arose and explain how critical thinking and problem-solving skills were used for the drug development process to continue.

Stay tuned for more information about this exciting new BIG IDEAS project!

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Science Policy

Federal Funding Levels for Science Agencies Uncertain Despite Bipartisan Support The passage of the omnibus spending bill last December yielded positive results for major science agencies, who received muchneeded increases to help in mitigating the continued effects of 2013’s sequestration.

The Bipartisan Budget Act of 2015 lifted the spending caps by $80 billion, or 3.9%, over two years, so the appropriations committees are able

to move forward regardless of a full congressional budget resolution. In fiscal year (FY) 2016, the discretionary spending cap increased by 5.2%, which brought a $2 billion boost for the National Institutes of Health (NIH). For the current year, there is an almost 6% increase for research and development (R&D). Appropriators on both sides of the aisle have voiced support for biomedical research and backed it up with votes

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and legislation, but the funding constraints in the agreement make FY 2017 allocations less certain. The caps will remain fundamentally flat for FY 2017, which will make spending levels for the year only slightly above sequestration levels; a situation not unlike the circumstances of two years ago, again following a two-year budget agreement. Also similar is the added factor of an election year, leading many legislators to resist controversial votes across party lines and spend more time campaigning in their districts.

Meanwhile, the Obama administration’s science budget request for FY 2017, which includes discretionary spending and previously-approved mandatory spending, would increase overall R&D to $148.8 billion, an increase of 1.4% above FY 2016 levels. That is less than the rate of inflation. But with the additional R&D requested through mandatory spending, the total would reach $152.9 billion, a 4.2% increase.

It is likely that the President proposed mandatory spending to circumvent the discretionary spending caps. Many argue, however, that the challenges

of mandatory spending ultimately outweigh the benefits. For example, new mandatory spending is subject to pay-as-you-go (PAYGO) rules, meaning it must be deficit-neutral and offset by revenue increases or spending cuts elsewhere. Appropriators are historically weary of mandatory spending, as it essentially removes their oversight of how dollars are allocated. The President’s proposal did succeed in resurrecting the conversation on mandatory vs. discretionary funding, and many have suggested it will be considered again in future cycles.

House Speaker Paul Ryan (R-WI) initially stated that he hoped to have all appropriations bills passed through the House in July. The current outlook, however, with continued conflict among the congressional majority, the threat of policy riders, and elections, suggests that we may be in for another fourth quarter of heated negotiations and continuing resolutions.

ASPET Submits Testimony to Congress on the Importance of NIH Funding in the FY 2017 Appropriations Cycle The House and Senate appropriations committees solicited testimony on funding priorities from stakeholder organizations as they began their work on the fiscal year (FY) 2017 budget for the federal science agencies. ASPET responded with statements to the appropriations subcommittees on Labor, Health and Human Services, and Related Agencies (LHHS) in both the House and the Senate.

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The testimony outlines the importance of sustained funding and appreciates the $2 billion increase for NIH in FY 2016; urging Congress to continue their support for biomedical research with a recommendation of $35 billion for NIH in FY 2017.

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Testimony of Kenneth E. Thummel on behalf of The American Society for Pharmacology & Experimental Therapeutics (ASPET) Submitted for the record to the Senate Committee on Appropriations Subcommittee on Labor, Health and Human Services, Education, and Related Agencies Senator Roy Blunt, Chairman; Senator Patty Murray, Ranking Member Regarding

Council Kenneth E. Thummel President University of Washington

David R. Sibley

President-Elect Bethesda, Maryland

Annette E. Fleckenstein Past President University of Utah

Fiscal Year (FY) 2017 Appropriations for the National Institutes of Health

Dennis C. Marshall

• Steady and sustained investment in NIH is critical to improving human health, stimulating state and local economies, and maintaining the nation’s global competitiveness.

Charles P. France

• The short-term implications of decreased funding for NIH is that only 1 out of 6 grant applications are funded, the lowest rate in the agency’s history, leaving unfunded many highly innovative ideas that have important implications for human health.

Paul A. Insel

• The long-term implications of a lack of sustained federal investment in biomedical research are more dire: the U.S. share of global research and development will decline, as a consequence of increasing research-related spending by China, Russia, and the European Union. In addition, an increasing number of scientists who trained in and/or working in the U.S. will leave to pursue careers in other countries, further compromising our competiveness and leadership in the health sector of the global economy.

Secretary/Treasurer Ferring Pharmaceuticals, Inc. Secretary/Treasurer-Elect University of Texas Health Science Center –- San Antonio Past Secretary/Treasurer University of California – San Diego

John D. Schuetz

Councilor St. Jude Children’s Research Hospital

Margaret E. Gnegy

Councilor University of Michigan Medical School

Wayne L. Backes

Councilor Louisiana State University Medical Center

Mary E. Vore

Chair, Board of Publications Trustees University of Kentucky

Brian M. Cox

FASEB Board Representative Uniformed Services University of the Health Sciences

Scott A. Waldman

Chair, Program Committee Thomas Jefferson University

Judith A. Siuciak

Executive Officer

• Lawmakers must secure a bipartisan, balanced approach to deficit reduction so that vital investments in biomedical research can be sustained in the best interests of the nation.

• We call upon Congress to ensure that NIH remains a national priority, by awarding an FY2017 minimum budget of $35 billion to restore purchasing power lost over the last decade and to increase the pool of talented young scientists who pursue a career in biomedical research that will advance the health of the American people.

The American Society for Pharmacology and Experimental Therapeutics (ASPET) respectfully submits the following testimony regarding Fiscal Year (FY) 2017 federal appropriations for biomedical research. ASPET is a 5,100-member professional society, whose members conduct basic, translational, and clinical pharmacological research within the academic, industrial and government sectors and are educators of research, medical, dental, pharmacy and other health professionals. Our members discover and develop new therapeutic agents that fight existing and emerging diseases, and disseminate that knowledge to improve human health. Sustainable, consistent funding for research is critical to the development of new disease prevention and treatment modalities. To this end, ASPET recommends a minimum of $35 billion for NIH in FY 2017.

Overview ASPET recognizes and very much appreciates the investment in research made by Congress with the $2 billion increase in funding for NIH included in the FY2016 omnibus appropriations bills. However, sustained commitment from Congress in FY 2017 is essential to mitigate losses from budget sequestration initiated in FY 2013. From 2003-2013, NIH budget failed to keep pace with inflation in research costs leading to a nearly 25% reduction in the agency’s purchasing power and 34% reduction in the primary grant mechanism that supports investigator-initiated research. Budget sequestration since 2013 has effectively codified the loss. A FY 2017 budget of $35 billion would help restore the agency’s lost purchasing power that has occurred over the past decade and enable the NIH to fund 465 more research grants.

9650 Rockville Pike | Bethesda | MD | 20814-3995 P: (301) 634-7060 | F: (301) 634-7061 | E: info@aspet.org | www.aspet.org

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Diminished Support for NIH Will Negatively Impact Human Health Industry, venture capital, and private philanthropy can supplement some elements of health research but they cannot replace the investment in basic, translational and clinical biomedical research provided by NIH. Much of the research undertaken by industry builds upon the discoveries generated from NIH-funded projects. The majority of NIH’s investment in basic biomedical research is broad with a long-term commitment, thereby providing an ongoing source of discoveries that are utilized by commercial entities to manufacture and market diagnostics, drugs and devices. Many such entities have shrunk their research and development programs and thus, are making smaller commitments to invest in research that may be of higher risk and require several years to fully mature. High-risk but high impact efforts, especially in basic research, represent the essential role played by NIH and its funded investigators.

Past investment in NIH-funded basic research has led to many innovative medicines. In addition, NIH-funded research has provided major gains in our knowledge of the human genome, resulting in enhanced drug efficacy and a reduction in adverse drug reactions that currently limit the effectiveness of potential life-saving medications. NIH is the world leader in efforts to prevent and treat HIV-AIDS; recent genetic studies have pinpointed disease-causing variants that have led to improved cure rates, but further advances and improvements in technology will be delayed with diminished NIH funding. The evolution of patient care into what has been termed “personalized” or “precision medicine” and its application to a wide range of clinical disorders, including cancer, necessitates research to identify and test optimal diagnostic and therapeutic approaches for individuals. Past investigator support from NIH has revealed new frontiers of immunopharmacology and regenerative medicine, which are saving millions of dollars by reducing in-patient hospital care for debilitative autoimmune diseases, such as rheumatoid arthritis, and restoring movement and function through regenerative interventions. Moreover, NIH is the only health organization capable of mounting an effective response to understand the mechanisms and develop treatments for rapidly emerging infectious diseases such as the Zika virus. Enhanced and sustained funding of NIH is essential for continued improvements in the prevention and treatment of these and many other diseases.

Investing in NIH Helps America Compete Economically NIH research funding catalyzes private sector growth. More than 83% of NIH funding is awarded to over 3,000 universities, medical schools, teaching hospitals and other research institutions in every state in our nation. One national study found that combined federal and state funded research at the nation’s medical schools and hospitals supports almost 300,000 jobs and adds nearly $45 billion to the U.S. economy. NIH funding also provides the foundation for major scientific innovations in the pharmaceutical and biotechnology industries, with new drug targets being discovered through NIH-supported basic research that can then be translated into novel drug treatments. Thus, an investment in NIH will help create jobs and promote economic growth. By contrast, a stagnating NIH budget will mean forfeiture of future discoveries and jobs to other countries, which are eager to “pick up this slack”.

If funding for the next ten years is similar to that of the past decade, the nation will lose a generation of young scientists. Increasingly, these individuals, seeing no prospects for careers in biomedical research, will leave the research enterprise or look for employment in foreign countries. The “brain drain” of young scientific talent seriously jeopardizes the nation’s leadership in biomedical research and compromises future advances in the prevention and treatment of disease. A 2013 survey of ASPET’s membership revealed that 45% of post-doctoral trainees and 25% of graduate students say they are no longer considering a career in biomedical research due to the restrictive funding environment; 50% of graduate students and 29% of post-doctoral trainees say they are willing to consider leaving the U.S. in order to pursue a career in biomedical research.

It is a sobering fact that the U.S. share of global research and development investment has declined substantially over that last two decades. In contrast, other nations are investing aggressively in science. For example, China has grown its science portfolio with annual increases to the research and development budget averaging over 20% annually since 2000. Russia plans to increase support for research substantially over the next decade. The European Union, despite great economic distress among its member nations, has proposed to increase spending on research and innovation by 45% between 2014 and 2020. All of these nations recognize the long-term economic value of scientific research and they are prioritizing their budgets accordingly.

Conclusion ASPET acknowledges the many competing and important spending decisions that are made by the Subcommittee. However, NIH’s contribution to the nation’s economic well-being and to the health of its citizens should make it one of the nation’s top funding priorities. Ensuring a long-term commitment to discovering cures for disease is one major way in which we can work together as a Nation to reduce Medicare Medicaid expenditures without cutting benefits. Moreover, investment in research today has the potential, through new discoveries, to improve the quality, while lowering the cost of, health care, especially through efforts on the major causes of death of Americans. Lawmakers must replace sequestration in 2016 and beyond with a bipartisan, balanced approach to deficit reduction so that vital investments can be made that are in the best long-term interest of the nation. With enhanced and sustained funding, NIH can begin to reverse the decline in its operational footprint and help achieve its potential to address the most promising scientific opportunities and critical healthcare needs of our country. A budget of at least $35 billion in FY 2017 will build on the progress of the FY2016 funding, expand opportunities for investigation and increase the likelihood of new discoveries that prevent, diagnose, and treat disease.

9650 Rockville Pike | Bethesda | MD | 20814-3995 P: (301) 634-7060 | F: (301) 634-7061 | E: info@aspet.org | www.aspet.org

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ASPET Washington Fellows Visit Congress

Lauren Haar of Loyola University of Chicago following her meeting with Senator Sherrod Brown (D-Ohio).

For the fourth consecutive year, ASPET’s Washington Fellows traveled to Washington, DC for meetings with their congressional delegations to discuss the importance of funding for biomedical Susanna Aguirre, ASPET’s manager of government affairs and science policy, research; making the case for steady Congressman James P. McGovern (MA-02), and Allyson Marshall of the University and sustained support for the National of Massachusetts School of Medicine.

Institutes of Health.

The 2016 Fellows, comprised of 2015 Washington Fellow Philip Saccone, a eleven graduate students, postdoctoral graduate student from the University of Michigan scientists, and junior faculty, visited fifty-seven Medical Center, appropriately asserts that effective congressional offices from all over the country. advocacy requires a consistent effort for a relatively Fellows informed their congressional delegation that long period of time: “Advocates need to make an their home institutions are under great stress, with effort to build a relationship with members and their pharmacology and other related departments often staff, and to be a resource for them on a particular smaller than they were just a few years ago. Fellows issue. The political landscape is always shifting, questioned the viability of their institutions and the and you never know where or when an opportunity country’s biomedical research enterprise if the next will arise—it may appear in the most unlikely of decade is anything like the past ten years. Another circumstances and be delivered by the most unlikely recurring theme was that once labs close and jobs people. Much like research, advocacy requires are lost, it is very difficult to bring the infrastructure persistence and resilience. If you’re not involved, and intellectual capital back in their home districts. you can’t expect to have a seat at the table when Fellows did an excellent job of incorporating state something important comes up.” funding data into their discussions, and all of them ASPET would like to thank and acknowledge the offered to make themselves available to their commitment and great effort by the 2016 Washington congressional offices as a future resource or host at Fellows for being great representatives of ASPET, their respective institutions. advocates for biomedical research, and future leaders!

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2017 Washington Fellows Program Submit your application by September 6, 2016 S Program Mission

Who Should Apply?

The mission of the ASPET Washington Fellows Program is to enable developing and early career scientists interested in science policy to learn about and become more engaged in public policy issues. Fellows will develop an understanding of how public policy decisions made in Washington help shape and impact science policy, such as funding for the National Institutes of Health and other science agencies. Fellows will also learn how to advocate effectively on Capitol Hill and in their home districts. This program will help Fellows develop the skills and insights to become future leaders in science.

The ASPET Washington Fellows Program is open to any graduate student, postdoctoral trainee, or researcher no more than four years past the completion of his/her postdoctoral training. Applicants must be members of ASPET in good standing and have a strong interest in science and its intersection with public policy. Fellows will be selected by the ASPET Science Policy Committee.

What Will ASPET Fellows Do?

All applications must contain the following information and be submitted by September 6, 2016, as a single combined PDF:

 Advocate on Capitol Hill: ASPET Fellows will come to Washington, DC, to meet with their congressional delegation to advocate for biomedical research and increased funding for the NIH. Fellows will be well trained by ASPET and prepared with the appropriate message to deliver to Congress. ASPET will cover transportation costs, hotel, and other reasonable expenses that follow ASPET’s reimbursement policy.  Become Advocates in their Home Districts: ASPET Fellows will meet with Members of Congress in their home district, act as a conduit to inform colleagues within their departments/institutions about federal legislative matters, write op-ed pieces to local papers, etc. All these activities will be undertaken with the support and advice of ASPET.  Attend the ASPET Annual Meeting at Experimental Biology 2017: ASPET Fellows will receive complimentary registration to attend the 2017 ASPET Annual Meeting in Chicago.

Application Information ASPET anticipates up to 10 Washington Fellows Program participants in 2017. Fellows serve one-year terms.

 A letter (no more than two pages) from the applicant stating their interest in public policy and why they are interested in the ASPET Washington Fellows Program  A Curriculum Vitae  A letter of support from the candidate’s mentor and/or department chair Incomplete applications and/ or applications received after September 6, 2016, will not be considered.

For more info: www.aspet.org/ASPET_Washington_Fellows_Program (301) 634-7060 publicaffairs@aspet.org The Pharmacologist • June 2016

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Education News Introducing the Pharmacology Education Project (PEP)

Many educators have scoured the Internet using a search engine to find just the right presentation or part of a presentation that can be used in teaching pharmacology. Students, too, use a search engine to find pharmacologyrelated content for their use in education or research. The results are often disappointing.

This was the rationale behind the creation of the International Union of Basic and Clinical Pharmacology (IUPHAR) Pharmacology Education Project (PEP).

With initial funding from the American Society for Pharmacology and Experimental Therapeutics (ASPET), the dream of a site where students and educators can find curated pharmacology content is becoming a reality. We are

pleased to announce the availability of the IUPHAR PEP website, www.pharmacologyeducation.org.

The IUPHAR PEP developed out of the need to deliver an online resource with a clear educational focus as a complement to the Guide to Pharmacology.

The IUPHAR PEP is a simple, attractive, easily searchable resource that supports students of pharmacological and other biomedical sciences such as medicine, nursing, and pharmacy, as well as those who teach them. The project should be particularly attractive to those in resource-poor countries or where pharmacology is less well developed.

The layout of the PEP website is divided into four main sections (Principles of Pharmacology, Principles of Clinical Pharmacology, Drugs, and Therapeutics), each comprised of several modules (e.g., adverse drug reactions under Principles of Pharmacology) that, in turn, are divided into topics (e.g. pharmacovigilance under adverse drug reactions).

The format for each topic includes a brief summary of the topic followed by curated and annotated links to other resources.

The Project is led by Simon Maxwell, secretary, IUPHAR-Education Section and University of Edinburgh, UK, and John Szarek, councilor, ASPET Division of Pharmacology Education and The Commonwealth Medical College, Scranton PA. They convened an inaugural Editorial Board comprised of an international group of educators and innovators in pharmacology education, including Leszek Wojnowski, University Medical Center, Mainz, Germany; Antonio Sarikas, Technische Universität, Munich, Germany; Elizabeth Davis, Monash University, Australia; Kelly Karpa, Penn State College of Medicine, United States; and Chay-Hoon Tan, National University of Singapore, Singapore. Elena Faccenda is the curator of the IUPHAR PEP website.

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The current resources found on the PEP website represent only the beginning of a project that we hope will grow rapidly and be utilized by the international community of pharmacologists. There is much more still to be developed, and we look forward to contributions from the international pharmacology community to expand the website’s offerings.

The IUPHAR PEP has the potential to significantly enhance pharmacology knowledge and learning across many disciplines worldwide. To achieve this, we need you to consider contributing materials and then point relevant learners (e.g., your students)

toward them. Whatever your research interests are in pharmacology, there will be a part of the site that you can contribute to or improve. Please take this opportunity to familiarize yourself with the site and then consider contributing to the project. We also are looking for partners to help with funding. Please write to us at admin@pharmacologyeducation.org.

Simon Maxwell, Co-Lead, IUPHAR PEP John L. Szarek, Co-Lead, IUPHAR PEP Elena Faccenda, Curator, IUPHAR PEP

ASPET Names 2016 Individual Summer Undergraduate Research Fellows The ASPET Summer Undergraduate Research Fellowship (SURF) program is designed to introduce undergraduate students to pharmacology research through a 10-week summer laboratory research experience. The goal of the program is to use authentic, mentored research experiences in pharmacology to heighten student interest in careers in research and related health care disciplines.

ASPET offers both institutional and individual SURF awards. Institutions with funded fellowship programs are listed at: http://bit.ly/1rbToje. The individual fellowships are designed to support students whose home campus lacks an institutional program or who seek more specialized training opportunities at a different university.

ASPET congratulates the six students selected for 2016 individual fellowships: William Capell, a student at the University of South Carolina, will conduct research with Dr. Michy Kelly at the University of South Carolina School of Medicine. Mr. Capell studies William Capell University of South Carolina

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the cAMP/cGMP-degrading enzyme PDE11A4, which is preferentially expressed in the hippocampal formation in the brain. Subcellular compartmentspecific dysfunction in cyclic nucleotide signaling is associated with neuropsychiatric disease. Mr. Capell aims to uncover the intramolecular signals controlling PDE11A4 compartmentalization and catalytic activity to identify novel mechanisms for therapeutically targeting this enzyme.

Ashton Faler, a student at the University of Findlay College of Pharmacy, will conduct research in the lab of Dr. Ryan Schneider.

Ms. Faler will build on Dr. Schneider’s lab’s efforts to investigate the anti-cancer effects of synthetic chalcone and flavonoid derivatives in several human glioblastoma Ashton Faler cell lines. Additionally, she University of Findlay will attempt to elucidate College of Pharmacy the mechanism(s) of these derivatives by investigating cell death pathways.

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Dillion Hutson, a student at Tulane University, will conduct research with Dr. Sarah Lindsey at the Tulane University School of Medicine.

Mr. Hutson’s project will characterize transcriptional effects of the G proteincoupled estrogen receptor (GPER). Although GPCRs are not normally associated Dillion Hutson with transcriptional effects, Tulane University research from Dr. Lindsey’s lab has consistently found that GPER activation induces genomic changes. Mr. Hutson will investigate whether these effects occur in response to cAMP activation or an alternative pathway.

Scott King, a student at Washington & Jefferson College, will conduct research with Dr. Catherine Davis at the Johns Hopkins University School of Medicine. Mr. King’s research will test therapies aimed at eliminating cognitive impairment following radiation exposure. He will evaluate the effectiveness Scott King of erythropoietin in reducing Washington & Jefferson these impairments using a College rodent behavioral model. His work is designed to address the lack of effective treatments for radiation-induced cognitive impairments and to better understand the mechanisms of radiation damage to the CNS.

Rebecca Spry, a student at Oglethorpe University, will conduct research in the lab of Dr. Kevin Murnane at Mercer University. Ms. Spry will study new treatments for Parkinson’s disease (PD), focusing on Omega-3 fatty acids that preserve neurons and normalize dopamine neurotransmitter levels. These Rebecca Spry are hallmark symptoms of PD, Oglethorpe University and current PD therapeutics do not address all of these symptoms.

Nathan Wainscott, a student at the University of Louisville, will conduct research in the lab of Dr. J. Christopher States at the University of Louisville School of Medicine. Mr. Wainscott will be testing the ability of several lead compounds targeting the anaphase promoting complex to arrest Nathan Wainscott the cell cycle and induce University of Louisville apoptosis in lung cancer cell lines. He will then determine the cell cycle phase in which this arrest is induced by the presence of specific cycle markers.

We wish the 2016 individual fellows as well as the fellows participating in the SURF institutional programs a productive and fun summer of research!

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Journals News New Editorial Board Members The Board of Publications Trustees is pleased to welcome the following new editorial board members since the last issue of The Pharmacologist.

Drug Metabolism and Disposition added Dr. Yurong Lai with Bristol-Myers Squibb and the University of Rhode Island to the Editorial Advisory Board.

Dr. Andrea Cignarella with the University of Padova joined the JPET Editorial Advisory Board.

Molecular Pharmacology’s Editorial Advisory Board added Dr. Henrik Dohlman, University of North Carolina, Chapel Hill; Dr. Kasper Hansen, University of Montana; Dr. Shelley Hooks, University of Georgia College of Pharmacy; Dr. Adriano Marchese, Medical College of Wisconsin; Dr. Robyn Meech, Flinders University of South Australia; Dr. Zhi Shi, Jinan University; Dr. Greg Tall, University of Rochester; Dr. Joanne Wang, University of Washington; and Dr. Wen Xie, University of Pittsburgh. Dr. Alan Smrcka, University of Rochester, is now an associate editor for the journal.

Improvements to Manuscript Submission Process ASPET’s journals will move to single PDF manuscript submission in the near future. Source files for text and images will not be required until acceptance once the new workflow is put into place.

Authors will submit a single PDF file containing the manuscript and all figures for initial submission and revisions. This should ease the submission process.

The manuscript submission system BenchPress implemented a drag-and-drop feature for ASPET’s journals recently. This makes it easier and much faster to upload source files.

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ASPET’s journals department staff members have been working with BenchPress to implement improvements to the manuscript submission process for authors, reviewers, and editors. Look for more improvements in the coming months. Although we work to prevent problems, staff members are available by email and telephone to step in when authors need help. Contact us at journals@aspet.org or by calling 301-634-7060 Monday through Friday from 8:00AM 5:00PM for assistance or to answer questions.

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Publish your paper in an ASPET Journal

Journals of the American Society for Pharmacology and Experimental Therapeutics

Inuential Journals...

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Membership News A Tribute to Dr. Dale Louise Birkle Dreer (1955-2016) Submitted by Lynn Wecker, PhD Dale Louise Birkle Dreer, chief of the Office of Scientific Review at the National Center for Complementary and Integrative Health (NCCIH), National Institutes of Health (NIH), passed away on Saturday, March 12, 2016 after a brief illness. Dale was Dr. Dreer born November 11, 1955 in Fort Eustice, Virginia. She received a BS in chemistry from Bridgewater College and a PhD in pharmacology and toxicology from the Medical College of Virginia in 1982 under the tutelage of Dr. Earl F. Ellis, investigating the effects of norepinephrine on arachidonic acid metabolism in feline cerebral cortex and murine neuroblastoma cells.

Following graduation, Dale pursued post-doctoral studies with Dr. Nicolas Bazan at the Louisiana State University Medical Center in New Orleans, where she studied arachidonic acid metabolism and lipoxygenase activity in the retina and cornea, and characterized the increase in free fatty acids in brain and neuronal cultures in response to increased neuronal activity.

In 1988, Dale accepted a faculty position in the Department of Pharmacology and Toxicology at West Virginia University (WVU) Medical Center led by Dr. Bill Fleming. During the 12 years Dale spent at WVU, she established an independent NIH-funded research program, mentored 4 PhD students, and rose through the ranks from assistant to full professor.

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Her initial focus characterized seizure-induced alterations in free fatty acids and diacyglycerols, following which she became very interested in stress and corticotropin-releasing factor. These studies represented the primary focus of Dale’s efforts until 2000, when she left academia to serve as a grants administrator for the National Center for Complementary and Alternative Medicine (NCCAM, which became NCCIH) at the NIH. Dale’s scientific expertise on brain structure and function, particularly as related to the consequence of drugs and environmental insult exposure, in concert with her commitment to research, led to her well-deserved promotion in 2009 to chief of NCCAM’s Office of Scientific Review.

In addition to her scientific endeavors, Dale was active in her community serving as parliamentarian for the American Society for Neurochemistry (ASN) from 1995-2001 and as a member of ASPET’s Program Committee from 2004-2009. At the ASPET Graduate Student-Postdoctoral Colloquium at EB2015 in Boston, Dale presented a talk entitled “Working for America” that was very interesting and well received by all.

Dale is survived by her husband Duane Dreer, her stepson Jacob Dreer, her sister Karen and her brother Kent and his wife Rene. Beyond her scientific expertise, Dale was known for her patience, infectious smile, and personality. We will all miss her greatly.

Dale was a member of ASPET since 1993.

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A Tribute to Dr. Nancy Rutledge Zahniser (1948-2016) Submitted by Habibeh Khoshbouei, PhD and Joanna Peris, PhD Dr. Nancy Rutledge Zahniser, PhD, passed away peacefully at her home in Denver, Colorado on May 5, 2016 after being diagnosed with neuroglioblastoma in December 2014. Dr. Zahniser was born on October 26, 1948 and raised in Chillicothe, OH. She Dr. Zahniser received a PhD in pharmacology in 1977 from the University of Pittsburgh. Dr. Zahniser did her postdoctoral training in the lab of Dr. Perry Molinoff in the Department of Pharmacology, School of Medicine at the University of Colorado Health Sciences Center (UCHSC) in Denver, CO. Subsequently, Dr. Zahniser was hired by the UCHSC Department of Pharmacology as a tenure-track assistant professor in 1981, rising quickly through the ranks to become full professor with tenure in 1991. Dr. Zahniser also held concurrent faculty appointments in the neuroscience program and the medical student training program at the University of Colorado School of Medicine.

Dr. Zahniser’s research focused on better understanding the brain neurotransmitter dopamine (DA) and the addictive drugs that alter its function.

She was the first to demonstrate that DA receptor binding is influenced by guanine nucleotides and that release regulating presynaptic D2 DA autoreceptors exist on rat striatal neurons. Her research was continuously funded by the National Institutes of Health (NIH) since 1981, including by RCDA, MERIT and Senior Scientist awards from the National Institute on Drug Abuse (NIDA). She was thoroughly committed to helping both graduate students and postdoctoral trainees advance their own careers, mentoring the research projects of 9 thesis students and 22 postdoctoral fellows in her lab. Together, they have published over 150 papers, reviews and book chapters. Many of Dr. Zahniser’s graduate students and postdoctoral trainees now run their own independent neuroscience laboratories.

In addition to serving as vice-chair and acting chair of the Department of Pharmacology from 2003-2006, Dr. Zahniser was also the CU School of Medicine associate dean for research education from 2007-2012, serving as a resource for persons applying for training grants, fellowships, and career awards. Dr. Zahniser directed an NIAAA-supported postdoctoral training grant, NIGMSfunded predoctoral pharmacology training grant and ASPET-supported Summer Undergraduate Research Fellowship program for under-represented students.

She served as a regular member of two NIH study sections, the NIDA National Advisory Council and the NIDA Intramural Research Program Board of Scientific Counselors, as well as an ad hoc member of numerous other National Science Foundation (NSF) and NIH review panels. In addition to a very active history of reviewing for all the major neuroscience and pharmacology journals, Dr. Zahniser was on the editorial boards of Pharmacological Communications, CNS Neuroscience and Therapeutics and the Journal of Neuroscience Methods.

Dr. Zahniser was a member of the American Society for Pharmacology and Experimental Therapeutics (ASPET) since 1982 and a member of the Society for Neuroscience since 1979. She received the Award in Excellence in Pharmacology/Toxicology from the PhRMA Foundation honoring her career achievements in the field of dopamine regulation in drug addiction in both 1984 and 2014. She served on the ASPET Council as Secretary–Treasurer in 2001– 2002 and was selected as a fellow in the prestigious Executive Leadership in Academic Medicine (ELAM) program for women in 2005–2006.

Dr. Zahniser’s absence will be felt by the multitudes of former students, post-docs and young faculty who Nancy tirelessly and generously supported over the years. She made a point at every scientific conference to attend their presentations, read their grant proposals and give them advice on new techniques or collaborations to further their careers. Nancy was a highly ethical scientist who was a role model for many.

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New Members REGULAR MEMBERS Eric Blomme, AbbVie, IL Mitsi A. Blount, Emory Univ, GA Dion R. Brocks, Univ of Alberta, Canada Amanda Brooks, North Dakota State Univ Alexander Bryant, Ironwood Pharmaceuticals, MA Ping Chen, Mayo Clinic, MN Shao-yu Chen, Univ of Louisville, KY Blaise M. Costa, Virginia Coll of Osteopathic Med Ivan L. Csanaky, Children’s Mercy Hospital & Clinics, MO Paul A. Davies, Tufts Univ - Sch of Med, MA Ellen J. Hess, Emory Univ - Sch of Med, GA Peter J. Houghton, Univ of Texas HSC, San Antonio Ying Huang, Western Univ of Health Sciences, CA Junguk Hur, Univ of North Dakota Takanari Inoue, Johns Hopkins Univ, MD Srinivas R. Iyengar, Icahn Sch of Med at Mount Sinai, NY Anand Iyer, Hampton Univ - Sch of Pharmacy, VA Shankaranarayanan Jeyakodi, OmniActive Health Technologies Inc., India Haitao Ji, Univ of Utah Vijaya Juturu, OmniActive Health Technologies Inc., NJ Kishore K. Katyayan, Eli Lilly & Company, IN Seher A. Khan, Lake Erie Coll of Osteopathic Med, PA Yu Shin Kim, Univ of Texas Med Branch Caroline Lee, Ardea Biosciences, CA Xue-Qing Li, AstraZeneca R&D Gothenburg, Sweden Michael P. Maher, Janssen R&D, LLC, CA Paul G. Mermelstein, Univ of Minnesota

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Grover P. Miller, Univ of Arkansas for Med Sciences Miguel Muzzio, IITRI, IL S. Priya Narayanan, GA Theresa V. Nguyen, Merck Research Labs, NJ Chidi I. Nosiri, Abia State Univ, Nigeria Ritu Singh, Corning Life Sciences, MA Kunhua Song, Univ of Colorado - Sch of Med David Sweatt, Vanderbilt Univ, TN Douglas D. Thomas, Univ of Illinois at Chicago Dong Wang, Univ of California, San Diego Thomas F. Woolf, Biotranex, NJ Zhengping Yi, Wayne State Univ, MI

POSTDOCTORAL MEMBERS Jonah S. Aprioku, Univ of Port Harcourt, Nigeria David I. Brown, Univ of North Carolina, Chapel Hill Sugasini Dhavamani, Univ of Illinois Matthew W. Gorr, CA Sandeep Kumar Kumar, Washington Univ - Sch of Med, MO Guruprasad Kuntamallappanavar, Univ of Tennessee HSC Dorwin Z. Lajot, DL Nutritional Consultancy & Supply, Philippines Daniel E. O’Brien, Vanderbilt Univ, TN Peter O. Oladimeji, St. Jude Children’s Res Hospital, TN

AFFILIATE MEMBERS Sarah R. Anthony, Univ of Cincinnati, OH Cindy B. McReynolds, EicOsis, CA

GRADUATE STUDENT MEMBERS Kodye L. Abbott, Auburn Univ, AL Mohammed M. Alhadidy, Univ of South Florida - Morsani Coll of Med William R. Arnold, Univ of Illinois, Urbana-Champaign Aria L. Byrd, Emory Univ, GA Gisela A. Camacho Hernandez, Univ Autonoma de Baja California, Mexico Kirti K. Chahal, Guru Jambheshwar Univ of Science & Technology, CA Somenath R. Chowdhury, CSIR-Indian Inst of Chemical Biology, Kolkata, India Emily E. Delman, Wright State Univ, OH Samuel C. Eaton, Univ of North Carolina Joseph O. Emudainohwo, Delta State Univ, Abraka, Nigeria Eric E. Figueroa, Vanderbilt Univ, TN Johanna Finn, Univ of Illinois at Chicago Courtney A. Follit, Southern Methodist Univ, TX Kuljeet Gugnani, MCPHS Univ, MA Joo-Hui Han, Chungnam National Univ - Coll of Pharmacy, South Korea Benedicta U. Iwuagwu, Robert Gordon Univ, UK Mohd M. Khan, Univ of Maryland School of Pharmacy, Baltimore Krishnaprasad G. Koorse, CoVAS Mannuthy, India Andrew G. Kunihiro, Univ of Arizona, AZ Montserrat A. Lara Velazquez, Johns Hopkins Univ, MD Ashok Mandala, CSIR-Indian Inst of Chemical Biology, India Michelle E. Martino, Rutgers Univ, NJ Tanzir B. Mortuza, Univ of Georgia Hannah V. Oakes, East Tennessee State Univ Bolape A. Oyekanmi, Federal Univ of Technology, Akure, Nigeria Anastasia Robinson, Howard Univ, DC

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Yalin S. Sahin, Hacettepe Univ, Turkey Aishwarya Sathyanarayan, Univ of Minnesota Shenghua Y. Sinkler, Univ of Missouri Dheeraj Soni, Univ of Illinois at Chicago Phillip A. Starski, Mayo Clinic, MN Andrew D. van der Vaart, Virginia Commonwealth Univ Brayden D. Whitlock, Univ of Alberta, Canada Aurellia Whitmore, Florida A&M Univ Andrew L. Willeford, Univ of California, San Diego Amirah F. Yusuf, Univ of Ibadan, Nigeria

UNDERGRADUATE STUDENT MEMBERS Savannah J. Afsahi, Nanomedical Diagnostics, CA Naishka Caldero, Univ of Puerto Rico William R. Capell, Univ of South Carolina Brandon D. Griess, California State Univ, Northridge Meagan E. Hackey, Roger Williams Univ, RI Lauren E. Harbaugh, St. Vincent Coll, PA Trinity A. Kronk, Emory Univ, GA Krista M. Lotesto, IL Abigail E. Moore, Michigan State Univ

Elsa J. Rosario, Queens Coll, NY Julie A. Rutkauskas, St. Vincent Coll, PA Eric J. Witherspoon, Morehouse Coll, MO George M. Yoshida, Univ of Cincinnati, OH

In Sympathy Dale Louise Birkle Dreer James Fisher Ronald L. Williams Nancy Rutledge Zahniser

We would like to congratulate Dr. Michael Tranter on being the grand prize winner of the $100.00 AMEX gift card for participating in the ASPET 2015-2016 Member-Get-A-Member program. All participants in the program received an ASPET logo T-shirt this year. Thanks to the recruiting effort of our members, we welcomed 19 new members this year through the Member-Get-A-Member program. We appreciate your contribution to the growth of ASPET.

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HOW TO GET INVOLVED IN

■ ASPET Annual Meeting/ASPET meetings • Submit a symposium proposal • Nominate a colleague, peer, or yourself for a scientific achievement award • Attend the ASPET Business Meeting and Awards Presentation at Experimental Biology (EB) • Participate at your division’s annual meeting at EB • Volunteer to help judge your division’s poster competition at EB • Submit an abstract to EB in an ASPET topic category • Give back to the community through the Day of Service at EB

■ Divisions • Send updates and ideas for consideration to your division’s Communications Officer (e.g., content suggestions for the web, news and achievements of fellow pharmacologists for Members in the News, LinkedIn discussion ideas) • Be sure to sign up for primary or secondary membership in divisions of interest • Join your division’s LinkedIn group page if they have one so you can contribute to the conversation • Students and postdocs: apply to be part of your division’s best presentation competition(s) at EB

■ Education • Order copies of Explore Pharmacology, ASPET’s booklet on careers, research, and other opportunities within the discipline, to hand out at your institution or at meetings • Suggest educational resources for the website

■ Journals • Contribute; use what you know to benefit the entire discipline by submitting papers • Volunteer; put your time and talent to good use by volunteering to review for any of our journals • Encourage your library to subscribe to ASPET’s journals or maintain the subscriptions they currently have

■ Leadership • Nominate a colleague, peer, or yourself for an elected position • Vote in elections and bylaws changes • Volunteer to serve on an ASPET committee – contact committee chairs about potential openings

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One of the questions we hear most frequently from members is “how

do I become

more engaged with the society?” Whether you are looking for leadership opportunities,

developmental experiences, networking, or a chance to be more involved in divisions and committees, there are many opportunities for engagement in the work of the society. Below are some of the ways you can contribute to ASPET while furthering your own growth and professional development.

■ Membership • Help grow the Society by participating in the Member-Get-A-Member recruiting program.

• Join one of ASPET’s regional chapters • Donate to any of our funds; contributions to ASPET funds help support research, travel awards, science advocacy and career development • Respond to ASPET surveys to help us improve your experience • If you are a department chair, encourage recruitment and/or participate in a recruitment campaign. ASPET can supply the chair with membership applications attached to a packet of membership information.

• Pass out ASPET marketing materials (e.g., member benefits pamphlet, brochures for programs of interest) to individuals you think would be interested (contact ASPET for details on obtaining materials)

■ Programs • Undergraduates and faculty mentors: apply for the Summer Undergraduate Research Fellowship program • Graduate students and post-docs: apply for the Washington Fellows program • Graduate students and post-docs: apply for the Mentoring Network program; faculty: apply to be a mentor

■ Science Policy • Contact your Congressional offices on the importance of appropriations for federally funded science agencies • Write an op-ed piece in your local newspaper regarding the importance of biomedical research funding

■ Writing • Propose a topic and submit a written article for consideration by The Pharmacologist; submissions can be sent to info@aspet.org • Contribute to Pharm Talk, ASPET’s blog for young scientists; submissions for consideration can be sent to info@aspet.org • Volunteer to write articles or news updates for your division to appear in The Pharmacologist or on the website; contact your division’s communications officer

These are some of the most common ways to get involved, but there are many possibilities for member engagement. We encourage you to reach out to us through info@aspet.org with your ideas. Here are some general tips to keep in mind: • Include detailed information in your request for getting involved, including specific aspects of the Society or area(s) of interest • Route your request appropriately; staff, division leadership, and committee leadership are generally the most appropriate points of contact. If you need more help contacting a specific individual, get in touch with us via info@aspet.org • Stay informed about opportunities by following us on Facebook and Twitter and reading our NewsBrief; make sure you are receiving our direct emails as well

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Members in the News Achievements, Awards, Promotions, and Scientific Breakthroughs Namandje N. Bumpus, PhD

Dr. Namandje Bumpus Johns Hopkins University

Dr. Atul Laddu Georgia Thrombosis Forum (GTF)

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Namandje Bumpus was recently named as one of 105 innovative scientists to receive a Presidential Early Career Award for Scientists and Engineers this year. This extremely prestigious award is the highest honor given by the United States government for early career investigators employed by or funded by a number of different departments or agencies. The award was conferred by President Obama in a ceremony at the White House.

Dr. Bumpus, currently an associate professor of pharmacology, has been on the faculty at Johns Hopkins University since 2010. She is funded by the Department of Health and Human Services with an R01 from the NIGMS titled “Cellular Signaling in Drug-induced Toxicity” and a U19 project from the NIAID titled “Tissue Pharmacology Imaging and Modeling.” Overall, her laboratory studies drug metabolism, focusing specifically on drugs used to prevent and treat HIV infection and determining whether genetic differences alter drug metabolism and thus clinical efficacy. Dr. Bumpus previously won the 2015 Division for Drug Metabolism Early Career Achievement Award for this work.

She has served as councilor of the Division for Drug Metabolism and will

be the Division Secretary/TreasurerElect starting July 1, 2016.

Dr. Bumpus has been a member of ASPET since 2008. She is a member of the Division for Drug Metabolism, the Division for Translational and Clinical Pharmacology, and the Division for Toxicology.

Atul Laddu, MD, PhD Dr. Atul Laddu founded Georgia Thrombosis Forum (GTF), an affiliate of the North American Thrombosis Forum (NATF). Under his direction, a team of volunteers has been working since 2012 to promote awareness of the deadly conditions of deep vein thrombosis (DVT) and pulmonary embolism (PE) in the state of Georgia.

Statistics indicate one clot develops every minute, and one patient dies of clots every six minutes. DVT and PE affect over 900,000 people in the United States annually, resulting in high mortality rates. An immediate need thus exists to spread public awareness and promote networks to support organizations such as the GTF. Dr. Laddu and Ms. Richa Bhome, a 9th grader and contributing author to this article, along with several other GTF volunteers have made significant contributions to spreading awareness of thrombosis in Georgia communities.

These include receiving recognition

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by Georgia Governor Nathan Deal awarding the GTF a proclamation for Thrombosis Awareness Month. The GTF is run with the efforts of young and adult community volunteers under the mentorship of Dr. Laddu. Many young GTF volunteers have written articles featured on the NATF website (www.natfonline.org) regarding educational activities and the work done by the volunteers in the community. Additional achievements for the GTF include media recognition and the Highest Award of Excellence to Dr. Laddu for community service

by Governor Deal. Dr. Laddu has also spearheaded opportunities for the GTF’s young members to receive internships at Harvard and Loyola Universities and to make presentations in front of faculty.

According to Dr. Laddu, the GTF’s future plans include moving forward with the young volunteers to conduct research in different countries and find relationships between different conditions and thrombosis.

The direction for the GTF is at the grassroots level because “the youth are the future of GTF, and the future is here.”

Dr. Laddu has been a retired member of ASPET since 1972. He is a member of the Division for Cardiovascular Pharmacology and the Division for Translational and Clinical Pharmacology.

Joanna Jacob Joanna “Jacy” Jacob and Andrew van der Vaart, graduate students in the Department of Pharmacology and Toxicology at Virginia Commonwealth University won the 2016 Lab Grammy Song Parody of the Year Award for their video “We Found Drugs,” which parodied the song “We Found Love”

by Rihanna. They competed against ten videos from various scientific disciplines in this year’s Lab Grammy Song Parody competition. The video sends a humorous and educational message to students to consider pharmacology as a career. Ms. Jacob researches the effects of ethanol on opioid tolerance with Dr. William L. Dewey, professor and chair of the Department of Pharmacology and Toxicology at Virginia Commonwealth University.

Ms. Jacob has been a member of ASPET since 2015. She is a member of the Division for Neuropharmacology, the Division for Behavioral Pharmacology, the Division for Molecular Pharmacology, the Division for Toxicology, and the Division for Translational and Clinical Pharmacology.

Joanna Jacob Virginia Commonwealth University

GTF members

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Division News 2016 Division Award Winners 1 2

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(1) BEH Best Presentation Competition Winners (Poster Sessions) - In the postdoctoral scientist category, the top prizes were awarded to Jacques Nguyen (1st), Jessica Anand (2nd), Brenda Gannon (2nd), and Sarah Withey (2nd).

(2) BEH Best Presentation Competition Winners (Poster Sessions) - In the undergraduate student category, the top prizes were awarded to Caitlin Labay (1st) and Mary Logan (2nd).

(3) CVP Trainee Showcase Winners (Oral Sessions) - In the graduate student category, the top prizes for trainee talks were awarded to Kristin Luther (1st), Nadia Ayala-Lopez (2nd) (not pictured), and Goutham Vasam (3rd).

(4) DM Best Presentation Competition Winners (Poster Sessions) - In the graduate student category, the top prizes were awarded to Julie Lade (1st), Joseph Jilek (2nd), and Faith Stevison (3rd).

BEH = Division for Behavioral Pharmacology DCP = Division for Cancer Pharmacology CVP = Division for Cardiovascular Pharmacology DDD = Division for Drug Discovery and Development DM = Division for Drug Metabolism

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MOL = Division for Molecular Pharmacology NEU = Division for Neuropharmacology DPE = Division for Pharmacology Education TOX = Division for Toxicology TCP = Division for Translational and Clinical Pharmacology

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(1) DCP Best Presentation Competition Winners (Poster Sessions) - In the undergraduate student category, the top prize was awarded to Gloria Le (1st). In the graduate student category, top prizes were awarded to Chen Shan Woodcock (1st) and Kristan Cleveland (2nd). In the postdoctoral scientist category, the top prize was awarded to Shu Zhou (1st).

(2) CVP Best Presentation Competition Winners (Poster Sessions) - In the graduate student category, the top prizes were awarded to Krishnaraj Rathod (1st), Alexa Hendricks (2nd), Santosh Suryavanshi (3rd), and Lingxin Zhang (HM) (not pictured).

(3) BEH Best Presentation Competition Winners (Poster Sessions) - In the graduate student category, the top prizes were awarded to Rachel Altshuler (1st) and Fernando Moura (2nd).

(4) CVP Trainee Showcase Winners (Oral Sessions) - In the postdoctoral scientist category, the top prizes for trainee talks were awarded to Inigo Valiente-Alandi (1st) and Jacob Myerson (2nd) (not pictured).

(5) CVP Best Presentation Competition Winners (Poster Sessions) - In the undergraduate student category, the top prizes were awarded to Patrick Liu (1st) (not pictured) and Brendan Mullan (2nd).

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(1) TOX Best Presentation Competition Winners (Poster Sessions) - In the postdoctoral scientist category, the top prizes were awarded to Alessandro Venosa (1st) and Hailiang Liu (2nd) (not pictured).

(2) MOL Best Presentation Competition Winners (Oral Sessions) - In the postdoctoral scientist category, the top prizes for oral presentations were awarded to Jennifer Cash (1st), Laurel Grisanti (2nd), and Kathryn Luderman (3rd).

(3) DDD Best Presentation Competition Winners (Poster Sessions) - In the young scientist category, the top prizes were awarded to Jenaye Robinson (1st) and Amit Sharma (2nd).

(4) TOX New Investigator Award winner Jamie J. Bernard, PhD (5) MOL Best Presentation Competition Winners (Poster Sessions) - In the graduate student category, the top prizes for poster presentations were awarded to Jason Davis (1st), Doungkamol Alongkronrusmee (finalist), Jugajyoti Baruah (finalist), Robert Cameron (finalist), and Kathryn Livingston (finalist).

(6) TCP Young Investigator Platform Session Winners (Oral Sessions) - In the postdoctoral scientist category, the top prizes were awarded to Naeem Patil (1st) and Matthew Jennis (2nd).

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(1) TOX Junior Investigator Award winner Brian S. Cummings, PhD (2) NEU Best Presentation Competition Winners (Poster Sessions) - In the undergraduate student category, the top prizes for poster presentations were awarded to Tyler Hinshaw (1st) and Nicole Colon Carrion (2nd) (not pictured). In the graduate student category, the top prizes for poster presentations were awarded to Sumitra Pati (1st), Sophia Kaska (2nd), and Danielle Tomasello (3rd).

(3) NEU Best Presentation Competition Winners (Oral Sessions) - In the postdoctoral scientist category, the top prizes for oral presentations were awarded to Matthew Robson (1st), Erin Calipari (2nd), and Erin Bobeck (3rd).

(4) TCP Best Presentation Competition Winners (Poster Sessions) - In the graduate student category, the top prizes were awarded to Jamie Moscovitz (1st), Jeremy Miyauchi (2nd), Clark Sims (3rd), Mikeal Boberg (HM) (not pictured), and Blessy George (HM) (not pictured).

(5) TCP Best Presentation Competition Winners (Poster Sessions) - In the undergraduate student category, the top prize was awarded to Mark Wiley (1st).

BEH = Division for Behavioral Pharmacology DCP = Division for Cancer Pharmacology CVP = Division for Cardiovascular Pharmacology DDD = Division for Drug Discovery and Development DM = Division for Drug Metabolism

MOL = Division for Molecular Pharmacology NEU = Division for Neuropharmacology DPE = Division for Pharmacology Education TOX = Division for Toxicology TCP = Division for Translational and Clinical Pharmacology

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(1) DM Best Presentation Competition Winners (Poster Sessions) - In the postdoctoral scientist category, the top prizes were awarded to Sasmita Tripathy (1st), Luc Rougee (2nd), and Aanchal Mehrotra (3rd).

(2) TOX Career Award winner John D. Schuetz, PhD (3) TOX Best Presentation Competition Winners (Poster Sessions) - In the graduate student category, the top prizes were awarded to Katiria Flores (1st), Souvarish Sarkar (2nd), and Rachel Murphy (3rd).

(4) NEU Early Career Independent Investigator Award winner Ryan A. Drenan, PhD (5) TCP Young Investigator Platform Session Winners (Oral Sessions) - In the graduate student category, the top prizes were awarded to Amanda Stolarz (1st) and Brett McGregor (2nd).

(6) TCP Awards for the Early Career Faculty Showcase were given to Michelle Kimple and Avner Schlessinger.

(7) DPE Travel Awards for Pharmacology Educators were awarded to Katharina Brandl, PhD and Dovenia Ponnoth, PhD.

BEH = Division for Behavioral Pharmacology DCP = Division for Cancer Pharmacology CVP = Division for Cardiovascular Pharmacology DDD = Division for Drug Discovery and Development DM = Division for Drug Metabolism

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MOL = Division for Molecular Pharmacology NEU = Division for Neuropharmacology DPE = Division for Pharmacology Education TOX = Division for Toxicology TCP = Division for Translational and Clinical Pharmacology

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James R. Gillette Best Paper Award Each year the Division for Drug Metabolism presents two James R. Gillette Best Paper Awards: one for the best paper in the area of drug metabolism and the other for the best paper in drug transport and pharmacokinetics.

The Gillette award in the drug metabolism category was given to Yun-Chen Tien, PhD, for her work done in the laboratory of Xiaobo Zhong, PhD, at the University of Connecticut. Dr. Tien received a cash award and certificate, and this work was presented by Dr. Zhong at the James Gillette Award and Platform Session at the 2016 ASPET Annual Meeting in San Diego.

The award-winning paper was titled “Dose of Phenobarbital and Age of Treatment at Early Life Are Two Key Factors for the Persistent Induction of Cytochrome P450 Enzymes in Adult Mouse Liver,” and was authored by Y.C. Tien, K. Liu, C. Pope, P. Wang, X. Ma, and X.B. Zhong. The authors investigated possible consequences on adult drug metabolism after receiving drug treatment at neonate and infant stages. Phenobarbital was used as a model drug and mouse as an in vivo model to demonstrate that the phenobarbital dose and the age at which treatment occurred are the two key factors for the persistent induction of gene expression and consequential increases of enzyme activities of several tested P450 genes in adult liver. These results may stimulate studies to evaluate the long-term impacts of drug treatment with different doses at neonatal and infant ages in humans on drug metabolism, therapeutic efficacy, and drug-induced toxicity throughout the rest of life.

Dr. Tien has been a postdoctoral fellow in Dr. Zhong’s Lab since 2013. She received her PhD in pharmacology from China Medical University. In addition to this award, she also received the first place Best Presentation Award in the postdoctoral category at the 19th North American ISSX/29th JSSX meeting in 2014 and the first place Best Presentation Award in the postdoctoral category from the Division for Drug Metabolism at the ASPET Annual Meeting at EB2015.

Dr. Yun-Chen Tien, second from right, first row

Dr. Zhong is an associate professor of pharmacology and toxicology at the University of Connecticut, School of Pharmacy. He received a PhD degree in molecular biology from Wageningen University in the Netherlands and trained as a postdoctoral fellow in genomics at the Yale University School of Medicine. Dr. Zhong was an assistant and associate professor at the University of Kansas Medical Center before he joined the University of Connecticut in 2012. A former councilor of the Division for Drug Metabolism, he currently serves on numerous editorial boards and several NIH study sections, including Developmental Pharmacology and Environmental Epigenomics. Dr. Zhong is currently funded by the National Institutes of General Medical Sciences and the National Institute of Environmental Health Sciences at the NIH. Research areas in his laboratory include P450-mediated drug metabolism, developmental pharmacology, pharmacogenetics, and pharmacoepigenetics for precision medicine.

The Gillette Award honors the late NIH Pharmacologist James R. Gillette, Ph.D. (http://dmd. aspetjournals.org/cgi/reprint/31/12/1474.pdf ), who was a scholar, scientist, philosopher, and supervisor of pharmacologists worldwide. During his career, Gillette published more than 300 papers and chapters and co-edited seven books. He was considered a visionary and significant contributor to the field of drug metabolism and pharmacokinetics.

Read about the James R. Gillette Drug Metabolism Best Paper Award winner in the drug transport and pharmacokinetics category, Dr. Lilly East, in the March 2016 issue of The Pharmacologist: http://bit.ly/1piu9fm

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2016 Paul M. Vanhoutte Distinguished Lectureship in Vascular Pharmacology

Mark T. Nelson, PhD, winner of the Vanhoutte Distinguished Lectureship with Paul M. Vanhoutte, MD, PhD.

The Pharmacologist • June 2016

Dr. Mark Nelson delivered this year’s Paul M. Vanhoutte Distinguished Lectureship in Vascular Pharmacology titled “Capillaries as Decoders of the Neural Rhythm of the Brain: Translating Thought into Blood Flow.” This award is sponsored by the Division for Cardiovascular Pharmacology and was established to honor Dr. Vanhoutte’s lifelong scientific contributions to the field of endothelial and vascular smooth muscle biology and for his outstanding contributions to mentoring numerous prominent trainees in the field of vascular physiology and pharmacology. Dr. Nelson is the chair of the Department of Pharmacology and distinguished professor at the University of Vermont.

He received a $1000 honorarium, a custom designed crystal bowl, and travel expenses to the ASPET Annual Meeting at Experimental Biology 2016. Dr. Nelson was recognized for his significant contributions to the field of vascular pharmacology and for his exceptional mentoring and service to ASPET and the Division for Cardiovascular Pharmacology.

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Division for Pharmacology Education Inducts Three New Fellows into the Academy of Pharmacology Educators completing post-doctoral research at Weill Cornell Medical College and the University of Miami School of Medicine, she joined the faculty at Nova Southeastern University.

In 2009, she became part of the Founding Faculty for the University of Central Florida College of Medicine. In her 19 plus years of teaching, she has taught most topics in pharmacology to medical, dental, and optometry students and also to allied health undergraduates in both small classrooms and large lecturestyle classes. She received a travel award from ASPET’S Division for Pharmacology Education in 2013 and is currently serving on the Executive A. Laurel Gorman, PhD, Nicole C. Kwiek, PhD, and Thomas C. Westfall, PhD (not pictured) were inducted into the Academy of Pharmacology Educators pictured with Committee of DPE. She has received Carol Beck, PhD (center). multiple teaching awards for her excellence and creativity in teaching.

Her medical education research The Academy of Pharmacology Educators interests include the use of simulations, innovative was established in 2010 in order to recognize and blended learning teaching techniques, and individuals who have made exemplary contributions curriculum development and assessment, all in the to pharmacology education in one or more of context of pharmacology education. the following areas: student-teacher interaction, Academy inductee Nicole C. Kwiek, PhD is clinical innovative contributions, scholarly endeavors, assistant professor and director of undergraduate professional development, and service. Three new studies at the Ohio State University College of members were inducted into the Academy during Pharmacy. She received her BS in biochemistry the Annual Meeting of the Division for Pharmacology from Ohio State, a PhD in pharmacology from Duke Education at EB 2016. More information about the University, followed by a postdoctoral fellowship at the Academy, including application instructions and a Duke Center for Science Education. Since joining the roster of inductees, can be found at http://www.aspet.

OSU faculty, she has received the BS Pharmaceutical org/Education/Academy.

Sciences Distinguished Teaching Award three times.

Academy inductee A. Laurel Gorman, PhD received She currently co-directs the Generation Rx Initiative, her BS in interdisciplinary studies (neurosciences) a learning community of Ohio State faculty, staff, and from the University of Florida and her PhD in students studying the problem of prescription drug pharmacology from LSU Medical School. After abuse. This project, designed to prevent misuse and

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abuse of prescription medication, provides online educational materials and hands-on learning at Ohio State University’s Center of Science and Industry. She has developed and taught MOOCs on pharmacologyrelated topics through Coursera and iTunesU. Dr. Kwiek is the lead administrator and teacher of Ohio State University’s College of Pharmacy’s Pills, Potions, and Poisons science enrichment program for high school students.

Academy inductee Thomas C. Westfall, PhD is the William Beaumont Professor and chair emeritus of the Department of Pharmacology and Physiology at St. Louis University School of Medicine. He received his PhD from West Virginia University. Dr. Westfall has been actively teaching pharmacology to medical students and other health care profession students for over 52 years as part of the faculty at universities in Missouri, West Virginia, and Virginia. He has been a PhD supervisor for 27 PhD students, a postdoctoral mentor for 17 fellows, and has served on over 100 prelim or thesis committees for PhD or MD/ PhD students. Dr. Westfall has been honored with

multiple teaching awards at St. Louis University. He has authored or co-authored chapters in multiple pharmacology textbooks, particularly chapters related to autonomic pharmacology or neuropharmacology.

He has served on multiple ASPET committees and in leadership roles, including chair of the Division for Neuropharmacology (1991-1993). He was recognized in 2015 for having been an ASPET member for 50 years. His successful research career consisted of more than 28 NIH grants with more than $12 million in funding and a total of 103 years of support.

During his 34 years as chair of the Department of Pharmacological and Physiological Science at St. Louis University School of Medicine, Dr. Westfall hired and mentored many junior faculty and was the principal investigator on two NIH T32 training grants.

The Division for Pharmacology Education considers it a privilege to add these three educator scholars to the roster of the Academy of Pharmacology Educators and is greatly appreciative of the many contributions made by these three individuals.

Have You Joined a Division?

Take full advantage of ASPET Membership by joining a Division!

• Participate in creating scientific programming for the annual meeting • Network with people in your field at mixers, Division programs, and on each Division’s LinkedIn group • Participate in running the Division and planning activities • Receive special notices about events and activities of interest in your field

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2016 Division Mixers ASPET members attended division-sponsored mixers at EB2016 to network and socialize with friends and colleagues.

Many divisions held their award ceremonies and honored their out-going leadership at the mixers.

View our photo collection from the 2016 annual meeting on Flickr: http://bit.ly/1rU8yeo

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Chapter News Great Lakes Chapter 29th Annual Meeting, July 7th, 2016 The Great Lakes Chapter (GLC) of ASPET will hold its 29th Annual Scientific Meeting on Thursday, July 7, 2016 at the Feinberg School of Medicine, Northwestern University, Hughes Auditorium, Lurie Building, 303 E Superior Street, Chicago, IL. Check the GLC website www.aspet.org/GLC for more information about the 29th annual GLC meeting.

Abstracts are due by June 27th, 2016.

The meeting schedule includes: • Poster Session (8:30AM – 10:30AM) • Vendor Exhibit (8:30AM – 12:00PM) • Young Investigator Symposium (10:45AM – 11:45AM) • Lunch & Learn Career Workshop (12:00PM – 1:30PM)

The Pharmacologist • June 2016

•S ymposium: Basic and Translational Advances in Neurological Disease: From Signaling to Therapeutics (1:30PM – 4:45PM) Keynote: Dr. Alfred George (Northwestern University): “Therapeutic Targeting of Ion Channels in Genetic Epilepsy” Speakers: Dr. Eric Karran (AbbVie), Dr. Robert Vassar (Northwestern Univ.), Dr. Natalie Tronson (Univ. of Michigan), Dr. Anthony West (Rosalind Franklin Univ.)

• Poster Awards & Business Meeting (4:45PM – 5:30PM)

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VISIT THE ASPET CAREER CENTER TODAY! WWW.ASPET.ORG/CAREERCENTER/

WHAT YOU NEED: ASPET’S CAREER CENTER HAS IT Jobseekers:

Employers:

 No registration fee

 Searchable résumé database

 Advanced search options

 Hassle-free posting; online account management tools

 Sign up for automatic email notifications of new jobs that match your criteria

 Reach ASPET’s Twitter followers (over 1,000), LinkedIn Members (over 2,000), and email subscribers (over 4,000)

 Free & confidential résumé posting  Access to jobs posted on the National Healthcare Career Network (NHCN)  Career management resources including career tips, coaching, résumé writing, online profile development, and much more

 Post to just ASPET or to entire NHCN network  Sign up for automatic email notifications of new résumés that match your criteria  Job activity tracking

ASPET is committed to your success: The ASPET Career Center is the best resource for matching job seekers and employers in the pharmacology and related health science fields. Our vast range of resources and tools will help you look for jobs, find great employees, and proactively manage your career goals.

9650 Rockville Pike, Bethesda, MD 20814-3995 Main Office: 301.634.7060 www.aspet.org

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Explore Pharmacology Graduate Studies in Pharmacology Promote your graduate program in our 2016 edition of Explore Pharmacology. This publication gives college students an overview of the fundamentals and applications of pharmacology.

In addition, it describes the many employment opportunities that await graduate pharmacologists and outlines the academic path that they are advised to follow. There is no better place to advertise your graduate program!

Benets of Advertising with Explore Pharmacology: Distributed to 1,100+ undergraduate students and ASPET Undergraduate Student Members who have a direct interest in pharmacology and related graduate programs Distributed at the Annual Biomedical Research Conference for Minority Students (ABRCMS), the Society for Advancement of Chicanos and Native Americans in Science (SACNAS) meeting, and the Society for Neuroscience Annual Meeting where over 30,000 attendees are expected

Explore Pharmacology Graduate Studies in Pharmacology

Copies will be sent to each of the 21 universities that participate in ASPET’s Summer Undergraduate Research Fellowship (SURF) program

Advertising Opportunities

American Society for Pharmacology and Experimental Therapeutics www.aspet.org

Advertise with a ¼ page, ½ page, or full page, 4-color display ad Enhance your visibility by advertising on one of the covers (inside front, inside back, or back cover) with a full page, 4-color ad Your ad will be highlighted on the ASPET Departments and Training Programs in Pharmacology webpage with a link to your website from September 1 - December 31, 2016

Act quickly, the Space and Materials deadline is Friday, July 15.

If you have questions or would like to see sample ads, contact ASPET’s advertising department: Jason Wells Advertising Manager jwells@faseb.org 301.634.7117 www.faseb.org/adnet/aspet The Pharmacologist • June 2016