June 2015 - The Pharmacologist

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the

A Publication by The American Society for Pharmacology and Experimental Therapeutics

Pharmacologist Vol. 57 • Number 2 • June 2015

How the Humble Horseshoe Crab Saves Lives

Inside: Farewell Message from the President EB 2015 in Review Call for Award Nominations

June 2015 • The Pharmacologist

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

Contents...

71 Message from the President 72 EB 2015 in Review 78 EB 2015 Program Highlights 82 Fun Stats from EB 2015 85 Call for Award Nominations 88 Feature Story: Blue Bloods: How the Humble Horseshoe Crab Helps Save Human Lives

97 Science Policy News 106 Education News 110 Journal News 114 New Membership 116 In Sympathy – Dr. William Fleming 118 Members in the News 119 Division News 130 Meetings & Congresses

THE PHARMACOLOGIST PRODUCTION TEAM Prateeksha Nagar Suzie Thompson Rich Dodenhoff Judith A. Siuciak, PhD COUNCIL President Annette E. Fleckenstein, PhD President-Elect Kenneth E. Thummel, PhD Past President Richard R. Neubig, MD, PhD Secretary/Treasurer Paul A. Insel, MD Secretary/Treasurer-Elect Dennis C. Marshall, PhD Past Secretary/Treasurer Sandra P. Welch, PhD Councilors Charles P. France, 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: $20.00 for ASPET members; $45.00 for U.S. nonmembers and institutions; $70.00 for nonmembers and institutions outside the U.S. Single copy: $20.00. Copyright © 2015 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: It has been my privilege to serve as president of the American Society for Pharmacology and Experimental Therapeutics (ASPET). It has been a year highlighted by many positive changes that are directly attributable to the outstanding efforts of those in the ASPET office. These consist of important improvements in communications with ASPET members, including a fresh new look for both The Pharmacologist and the ASPET website. Cooperative initiatives with the International Union of Basic and Clinical Pharmacology continue. A Division for Cancer Pharmacology was initiated. Important new journal features were initiated, including the introduction of visual abstracts, CrossCheck/iThenticate, and revised instructions to authors that proactively and enthusiastically support the NIH-Nature-Science/AAAS workshop-initiated Principles and Guidelines for Reporting Preclinical Research.

Legislative outreach continues, including visits to Capitol Hill in efforts to advocate for sustained funding from the National Institutes of Health (NIH) and other agencies so as to ensure a bright future for biomedical research. Interaction with the NIH and other important thought leaders continues, as evidenced in part by the inaugural Presidential Symposium at EB 2015.

Both the David Lehr Research Award and the Reynold Spector Award in Clinical Pharmacology were presented for the first time. ASPET continues to be very grateful to Mrs. Lehr and to Dr. and Mrs. Spector for their very generous support of the Society.

During the past year, ASPET has invested substantial resources toward supporting young scientists.

As one example, three inaugural BIG IDEAS initiatives were launched, with particular emphases on undergraduate education, mentoring and diversity, and partnering with industry. As another example, the Mentoring and Career Development Committee provided exceptional programming for young scientists at the recent Experimental Biology meeting. Young scientists are key to the future of the discipline of pharmacology, and their support must continue to be a key priority for the Society.

I sincerely thank both the ASPET staff and the ASPET Council for their tremendous efforts this year. I also thank the Division leadership, who have met regularly this year and have cooperated to initiate many improvements for the membership. Finally, I express gratitude to the ASPET membership for the opportunity to serve the Society as its president.

Sincerely,

Annette E. Fleckenstein

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EB 2015

IN REVIEW The ASPET Annual Meeting at Experimental Biology 2015 took place on March 28–April 1, 2015 in Boston, MA. With over 14,300 attendees this year, we held a highly successful meeting with very well attended sessions, fun social events, great networking opportunities, and a bustling booth in the exhibit hall.

ASPET members filled the room on Saturday, March 28 to attend this year’s business meeting. President Annette Fleckenstein updated members on the Society’s current activities, programs, and initiatives.

Highlights included the 2015 ASPET election results, an announcement about our new Division for Cancer Pharmacology, information about improvements made to member communications, such as The Pharmacologist and the new annual meeting website, an introduction of ASPET’s new Education Manager, Dr. Catherine Fry, and an update on the 3 BIG IDEAS chosen from our 2014 BIG IDEAS initiative. Members

Mrs. Lehr speaking at the awards ceremony

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in attendance discussed and voted on sending three bylaws changes forward to the membership-atlarge. Reports were given from the ASPET Finance Committee and the Board of Publications Trustees.

Finally, the 2015 ASPET award winners were recognized and presented their awards. It was an honor to have Mrs. Lisa Lehr and Dr. Reynold Spector, who both gave moving speeches, with us at the business meeting to help present the inaugural awards for the David Lehr Research Award and the Reynold Spector Award in Clinical Pharmacology, respectively.

2015 ASPET Scientific Achievement Award Winners

Dr. Spector speaking at the awards ceremony

73 2015 ASPET Young Scientist Travel Award Winners Incoming President Kenneth Thummel thanks President Annette Fleckenstein for her services.

2015 SURF Travel Award Winners

2015 Washington Fellows Travel Award Winners

2015 ASPET Graduate Student Travel Award Winners

Following the ASPET Business Meeting, members celebrated the start of the 2015 Annual Meeting with an opening reception. With over 300 people in attendance, members enjoyed great food, an open bar, and a lively atmosphere to catch up with old and new friends.

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74 The ASPET booth in the exhibit hall had very good traffic this year, and our booth activities were vibrant and successful. We signed up a record number of new members with 103 new applications. This included 10 new regular members, 2 new postdoc members, 39 new graduate student members, and 52 new undergraduate student members. We also offered two new products for sale in our store, a men’s necktie

ASPET Exhibit Hall Booth

Dr. Myron Toews models the new ASPET necktie.

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Meet-A-Mentor

and a ladies’ scarf. We sold 124 items, with the ASPET plush donkey still being our number one selling item. If you didn’t get a chance to purchase an ASPET logo’d product at the meeting, you can make purchases online at www.aspet.org/store. We also hosted a Meeta-Mentor event at our booth where students signed up for appointments to meet with members of the Mentoring and Career Development Committee.

75 The Student and Postdoctoral Best Abstract Competition gave students and young scientists a chance to present their work in a lively and fun atmosphere. All ASPET divisions held their competitions simultaneously.

The competitions provided a great opportunity for 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.

Best Abstract Competition

Also, given out at the Student and Postdoctoral Best Abstract Competition was the 2015 Dolores C. Shockley Best Abstract Award. 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 2009, Dr. Shockley received the Distinguished Alumni Award from her alma mater, Purdue University. First place was awarded to Dominique Jones from the University of Louisville for her abstract entitled “miR-186 Inhibition Alters Cell Proliferation and Colony Formation in Prostate Cancer,” second place went to Alina Monteagudo from the University of Rochester for her abstract entitled “Transglutaminase 2 as a Possible Chemotherapeutic Target in Glioblastoma Multiforme,” and third place was shared by Kerri Pryce from SUNY-Buffalo for his abstract entitled “Regulation of the sodium-activated potassium channel Slack by MAGI-1” and Ariell Joiner from the University of Michigan for her abstract entitled “The Role of Cilia in the Regulation of Olfactory Horizontal Dr. Ashley Guillory presents Dominique Jones, Alina Monteagudo, Ariell Joiner, and Kerri Pryce with the 2015 Dolores C. Shockley Best Basal Cells.”

Abstract Awards.

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76 Following the poster competition, ASPET Students and Postdocs socialized at the Student/Postdoc Mixer.

The room was packed with young members dancing and having fun with friends.

ASPET Student/Postdoc Mixer

On Friday, March 27, 2015, ASPET members spent the day volunteering at Cradles to Crayons, helping the children of Boston.

To view the full album of EB 2015 pictures, visit us online at: www.flickr.com/photos/ aspet_photo_gallery

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See Ne y xt ou Yea r!

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experimentalbiology.org

2016 San Diego April 2 – 6 Abstract Deadline: Friday, November 6, 2015

Annual Meetings of:

American Society for Investigative Pathology

American Society for Nutrition

American Society for Pharmacology and Experimental Therapeutics

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EB 2015 Program Highlights ASPET Presidential Symposium Navigating the Future of Biomedical Research

The inaugural ASPET Presidential Symposium titled “Navigating the Future of Biomedical Research” was held during the annual meeting at EB2015.

We were pleased to welcome the inaugural ASPET Presidential Symposium to our annual meeting at EB 2015. The symposium, which focused on “Navigating the Future of Biomedical Research”, was organized by ASPET President Annette Fleckenstein and highlighted challenging issues such as the evolving nature of careers in science, reproducibility, optimizing NIH-funded research, and pharmaceutical discovery and development. The panel included a diverse array of speakers who have worked in academia, government, and industry during their careers and brought to the symposium a valuable perspective on science in the 21st century.

Michael S. Teitelbaum, senior research associate at the Labor and Worklife Program at Harvard Law School, discussed the patterns and trends in science labor markets. Dr. Teitelbaum was Science Careers Person of the Year in 2013, which honors an individual who has made a significant and sustained

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contribution to the welfare of early-career scientists.

His book Falling Behind? Boom, Bust, and the Global Race for Scientific Talent, which examines the historic pattern of recurrent panics over supposed shortages of scientific talent, was released in March 2014.

Dr. Teitelbaum noted the productivity of US basic research but emphasized the need to implement policies to stabilize funding to avoid the recurring “alarm/boom/bust” cycles noted since the 1940s. He proposed “candidate stabilizers” such as aligning graduate education more with career prospects than research funds and emphasized the need to grow R&D in a steady, predictable manner through longerterm (e.g., 5 year) budget plans and counter-cyclicals (e.g., bridge funding).

Nancy L. Desmond, office director and associate director for Research Training and Career Development at the National Institutes of Mental Health (NIMH) discussed the National Institutes of Health (NIH) and NIMH mechanisms for enhancing the training of students and postdocs to better prepare them for careers, including developing professional skills that are transferrable, the use of Individual Development Plans (IDPs) in grant progress reports, the NIH Broadening Experiences in Scientific Training (BEST) program, and the NIMH Biobehavioral Research Awards for Innovative New Scientists (BRAINS) for early stage investigators.

Shai Silberberg, program director for the Extramural Research Program at the National Institute of Neurological Disorders and Stroke (NINDS), focused on “Assuring a Bright Future for Biomedical Research.” Dr. Silberberg’s lecture addressed the issue of reproducible experimental results head-on, describing the impact of bias, both unintentional and

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intentional, at all stages of research. He also discussed efforts to improve the rigor of science and the importance of professional integrity in research.

Phil Skolnick, director of the Division of Pharmacotherapies and Medical Consequences of Drug Abuse at the National Institutes of Drug Abuse (NIDA), delivered a talk titled “Navigating the Future of Drug Development: Calm Seas or Stormy Weather?” Dr. Skolnick, who has extensive experience in corporate and academic drug research, leads a team involved in phases of therapeutic drug development and clinical trial infrastructure. He described the challenges faced by the pharmaceutical industry, especially in the CNS disorders area, where significant decreases in returns on R&D investments have led to retreats from some therapeutic areas.

Dr. Skolnick noted contributing factors including the increasing availability of generics and the underdelivery of technology and genetics to contribute to new drug discovery. To address these challenges, he proposed an increasing decision-making role for scientists, a focus on identifying new drugs that improve upon current agents, and cited improved patent protection as an important incentive for future industry investment.

As the director of the Division of Pharmacology, Physiology, and Biological Chemistry at the National Institute of General Medical Sciences (NIGMS), Michael E. Rogers oversees the administration of more than 1500 research and training grants. Dr. Rogers summarized NIH/NIGMS new directions in supporting research in the context of the current funding environment. These include programs to fund investigators instead of projects, a new biosketch format that emphasizes contributions to science, and a revised grant resubmission policy at NIH. At NIGMS, transformative efforts are directed toward pursuing a broad and diverse research portfolio, new guidelines for funding investigators with substantial unrestricted research support, the MIRA (Maximizing Investigators’ Research Award) program, and mechanisms for providing training in scientific rigor and reproducibility. Dr. Rogers noted a recent increase in the success rate of funding at NIGMS after a long decline.

We look forward to next year’s ASPET Presidential Symposium, which will be organized by Dr. Ken Thummel.

Meet-the-Experts Lunch: Benchside-to-Bedside Research Sponsored by the Division for Translational and Clinical Research

The inaugural Division for Translational and Clinical Research Meet-the-Experts Lunch was held during the annual meeting at EB 2015.

The Division for Translational and Clinical Pharmacology (TCP) sponsored a “Meet the Experts Lunch: Benchside-to-Bedside Research” at the annual meeting in Boston. The session, which featured four prominent clinical pharmacologists from academia, industry, and government, was wellattended and gave the attendees insight into a diverse spectrum of viewpoints regarding where clinical and translational pharmacology is heading and how best to prepare

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ourselves for this transition. The lunch opened with a general introduction of the topic and speakers by the chair, Michael Holinstat, a translational pharmacologist working in basic and translational research in cardiovascular medicine at the University of Michigan.

Following general introductions, each of the speakers described their background and view points on where the field is heading and how best to traverse the challenges going forward.

Andre Terzic, a physician scientist at the Mayo Clinic who focuses on cardiovascular and regenerative medicine, opened with insightful comments regarding what are the important questions of today and possibly tomorrow and where he sees the field moving. His talk was followed by Darrell Abernethy, the associate director for drug safety in the Office of Clinical Pharmacology at the FDA, who discussed his experiences both in academia as well as government and what some of the challenges are moving forward as well as the potential areas for growth in the field. Next, the participants heard from George Christ, the director of Basic Science and Translational Research in Orthopedics at the

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University of Virginia. Dr. Christ discussed the exciting field of regenerative medicine and how this field, which is just beginning to come of age, will blossom over the next five to ten years and play a central role in benchside-to-bedside medicine.

The final speaker for the session was Scott Waldman, who is chair of the Department of Pharmacology and Experimental Therapeutics at Thomas Jefferson University. Dr. Waldman discussed how he was able to take a basic science discovery in his lab and translate this discovery into a clinical study and eventually a clinical trial. He further discussed the importance of following through with novel ideas and how the lab and clinic can work symbiotically to advance important clinical science concepts for unmet needs. Junior investigators including graduate students, postdoctoral fellows, and assistant professors, especially benefited from this session through direct interaction and question and answer periods with each of the speakers. The Division for Translational and Clinical Pharmacology is looking forward to continuing this “Meet the Experts” lunch series at next years’ meeting in San Diego.

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Explore Pharmacology Graduate Studies in Pharmacology Promote your graduate program in our Special Graduate Program 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, 2015

Act quickly, the Space and Materials deadline is Wednesday, 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

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Fun Stats at

EB 2015

Find Some Fun Stats Below to See How Well We Did at EB 2015 ASPET Booth

ASPET Sessions Most Popular ASPET Events

Thank you for visiting us at the ASPET booth!

We received double the number of new member applications from students at the ASPET booth in Boston than we had at EB 2014. The ASPET store did well too!

19%

of shoppers purchased the Einstein T-shirt

28% 13%

of shoppers purchased an ASPET donkey

of shoppers purchased a child-size T-shirt

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1 Julius Axelrod Award in Pharmacology Lecture 2 Graduate Student-Postdoctoral Colloquium: How to Get Started 3 Julius Axelrod Symposium: The Ins and Outs of G Protein-Coupled Receptor Signaling 4 Biased GPCR Signaling in Drug Development: From Theory to Physiology 5 Cardiac Fibroblasts: Fair-Weather Friends in Myocardial Fibrosis and Repair

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ASPET Events ASPET had 1 event in the top 2% of all EB events bookmarked on the Mobile App (Colloquium)

ASPET Members Go Mobile!

ASPET had 12 events in the top 10% of all EB events bookmarked on the Mobile App

Over 76% of EB participants downloaded the EB 2015 Mobile App! Top Bookmarked ASPET Events on the EB Mobile App:

Interest in Pharmacology is increasing at EB!

1 2 3 4 5

Graduate Student-Postdoctoral Colloquium: How to Get Started Julius Axelrod Award in Pharmacology Lecture The Human Microbiome: Systems Pharmacology Insights and the Potential for New Drug Discovery ASPET Opening and Awards Reception Speed Networking for Careers beyond the Academic Bench

• ASPET abstract submissions increased by 8% over last year.

• ASPET registrants increased by 13% over last year.

• The number of submissions to ASPET Travel Awards increased by 29%.

• The number of submissions to ASPET’s Best Abstract Awards increased by 15%.

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Call for Award Nominations ASPET Scientific Achievement Awards ASPET presents several major awards to recognize accomplishments either in specific areas of pharmacology or contributions to and accomplishments in the discipline in general. We will be launching a new online award nomination system by this summer. The deadline for nominations is September 15, 2015.

For more information about these awards and to access the new online nomination system, please visit: www.aspet.org/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 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.

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ASPET Division Sponsored Awards

The Robert R. Ruffolo Career Achievement Award in Pharmacology recognizes 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 was established in 2011 in recognition of the contributions made to drug discovery and development by Dr. Ruffolo.

The Louis S. Goodman and Alfred Gilman Award in Receptor Pharmacology was established in 1980 to recognize and stimulate outstanding research in pharmacology of biological receptors. Such research might provide a better understanding of the mechanisms of biological processes and potentially provide the basis for the discovery of drugs useful in the treatment of diseases.

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Sponsored by the ASPET Division for Drug Metabolism The B. B. Brodie Award in Drug Metabolism recognizes outstanding original research contributions in drug metabolism and disposition, particularly those having a major impact on future research in the field. This award was established to honor the fundamental contributions of Bernard B. Brodie in the field of drug metabolism and disposition.

Sponsored by the ASPET Division for Behavioral Pharmacology The P. B. Dews Award for Research in Behavioral Pharmacology recognizes outstanding lifetime achievements in research, teaching, and professional service in the field of behavioral pharmacology.

The award honors Peter Dews for his seminal contributions to the development of behavioral pharmacology as a discipline.

Sponsored by the ASPET Division for Cardiovascular Pharmacology The Paul M. Vanhoutte Distinguished Lectureship in Vascular Pharmacology was established to honor Dr. Vanhoutte’s lifelong scientific contributions to our better understanding and appreciation of the importance of endothelial cells and vascular smooth muscle function in health and disease and for his mentoring of countless prominent endothelial and vascular biologists and pharmacologists. This award includes a state-of-theart lecture on recent advances in vascular biology and pharmacology at the ASPET Annual Meeting.

Proposed amendments to ASPET bylaws have been approved by the membership-at-large. Thank you for voting! View the amendments here: www.aspet.org/2015_Proposed_Changes_to_Bylaws/

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Nominate Candidates for ASPET Awards Did your mentor have a profound impact on you and the pharmacology community?

Nominate them for the Axelrod Award.

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

Nominate them for the Abel 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.

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 know someone who is performing outstanding research in the pharmacology of biological receptors?

Nominate them for the Goodman and Gilman Award.

Exercise your membership benefits! Nominate someone who has made an impression on you.

Face it‌most of the time, research is a thankless job. What better way to give long deserved kudos to our everyday unsung heroes! Only ASPET members may nominate candidates for awards, so please make sure your membership is up-to-date.

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Blue Bloods: How the Humble Horseshoe Crab Helps Save Human Lives Rebecca J. Anderson

It all started with one sick crab.

Frederik Bang was spending the summer at the Marine Biological Laboratory in Woods Hole, Massachusetts, and contemplating his choices for research. He had his pick among a treasure trove of marine species in MBL’s Supply Department, stocked daily from the local fish catch. Horseshoe crabs were plentiful, and the sick one, in Frederik Bang particular, piqued his interest.

Bang was a pathologist and Photo by unidentified photographer.

Alan Mason Chesney Medical routinely used marine organisms Archives of The Johns Hopkins to gain insights into biological Medical Institutions. mechanisms of clinical significance. In the US Army Medical Corps, he had directed research studies on malaria and other tropical diseases in the South Pacific. After World War II, he joined the Medical School faculty at Johns Hopkins University and spent his summers rotating between field laboratories in France (Station biologique de Roscoff); Calcutta, India; and Woods Hole. At Roscoff, he studied a marine worm that produced a thick mucus, hoping to elucidate the mechanisms responsible for cystic fibrosis. In Calcutta, he studied parasites and diarrhea. In Woods Hole, he played around with oysters and marine worms, among other things.

In 1953, Bang was appointed chairman of the Department of Pathobiology at the Johns Hopkins School of Public Health. For his summertime research, he headed to Woods Hole, where he spotted that sick horseshoe crab. When it died, Bang conducted a necropsy to determine why. He discovered that the crab’s entire blood volume had clotted into a semi-solid gel (1). Thus began a cascade of landmark investigations and the discovery of a substance that has protected the lives of millions of patients.

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Characterizing the Clots In 1885, W. H. Howell first reported that blood withdrawn from the horseshoe crab “almost immediately” forms a solid clot (2). But most of what Bang learned about the jelly-like clots came from Leo Loeb. During his summer visits to Woods Hole in the 1920s, Loeb extensively studied horseshoe crabs and characterized the clotting phenomenon.

Blood circulating in the horseshoe crab (Limulus polyphemus) contains only one type of cell, the amebocyte: a clear, nucleated, oblong cell that is packed with granules. When Loeb placed blood on a glass slide, he observed that the amebocytes changed their shape and released their granules, which then formed a gel (3, 4). Loeb also observed that the amebocytes collected around certain foreign bodies, but he did not pursue studies to determine whether natural pathogens could trigger granule release and gel formation. Bang suspected the trigger was marine bacteria (1).

A colony of horseshoe crabs off the Atlantic coast.

Photo by Breese Greg, U.S. Fish and Wildlife Service. In the Public Domain.

Horseshoe crabs live on the soft sandy and muddy bottoms of near-shore seawater, which is teeming with bacteria—one billion bacteria per ml (5, 6). Some sort of bacterial infection had likely made the crab sick and caused the intravascular coagulation that Bang observed. Pursuing this possibility, he followed the guidelines established by Robert Koch, who had proposed criteria for determining that bacteria cause a given disease (7).

During the summers of 1953 and 1954, Bang extracted bacteria at random from fresh seawater and injected samples into a series of horseshoe crabs.

The injected bacteria “caused an active progressive disease marked by extensive intravascular clotting and death” (1).

In subsequent experiments, he isolated bacteria from naturally diseased animals and identified Vibrio, a rod-shaped Gram-negative bacterium (8). Under the microscope, Bang saw that bacteria caused amebocytes to change their shape and release their granules (1). When he mixed pure cultures of Vibrio with amebocytes, a “much heavier gel-like material” formed (8). The gel trapped and immobilized live bacteria within minutes.

All of these findings satisfied Koch’s postulates, but some of Bang’s observations seemed to refute the idea that his horseshoe crabs were suffering from a bacterial infection. He boiled bacterial suspensions to kill the bacteria and found “to our surprise” that the sterile liquid still “caused extensive intravascular clotting in a few minutes after injection” and killed the crabs within a few hours (1, 7). Also, when he added his sterile liquid to blood removed from healthy horseshoe crabs, it induced “a stable gel” (1). Bang concluded that the pathogen responsible for these effects was a heat-stable bacterial “toxin” (1).

By the early 1960s, Bang had learned as much as he could about the pathology of bacterial infections in the horseshoe crab. To study the clotting reaction further and to characterize the putative toxin, he needed the expertise of a hematologist.

While planning his next trip to Woods Hole, Bang called C. Lockard Conley, the founder and chairman of the Division of Hematology at Johns Hopkins. Conley headed an active research group studying blood coagulation, platelets, and hemorrhagic diseases, and Bang asked if Conley could recommend someone to assist with the blood clotting experiments.

To everyone’s surprise, the rather straight-laced and old-school Conley proposed Jack Levin, a young hematologist who had only recently joined his research group. Starting research fellows in Conley’s lab just didn’t get selected to spend a summer at such a prestigious facility (9). The Marine Biological Laboratory attracted biologists from all over the world, and its productivity was “equivalent to that of many of the country’s universities combined” (10).

Without exaggeration, Lewis Thomas said, “If you can think of good questions to ask about the life of the earth, it should be as good a place as any to go for answers” (10). So, when Conley asked him, Levin jumped at the opportunity. “Joining Dr. Bang,” Levin

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said, “was one of the smartest professional decisions I ever made” (9).

Jack Levin

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The Big Bang

Jack Levin

In the 1960s and 1970s, the Marine Biological Laboratory was a place “put together…by what can only be described as a bunch of people...It seems to have a mind of its own, which it makes up in its own way” (10). When Levin arrived, Bang handed him a horseshoe crab and said, “Go to it” (9). The large, intimidating creature had nine eyes, ten legs, and a long spikey tail protruding from its massive shell. But Levin soon discovered his experimental subject was docile, cooperative, and well suited to his studies.

Hemocyanin accounts for 90% of the cell-free protein floating in the plasma of horseshoe crab blood. This copper-containing protein turns blue when oxygenated, making the crab’s blood a milky shade of blue. When Levin separated the blood cells from plasma, he saw that (unlike the platelets in

Jack Levin collecting blood from a horseshoe crab at the Marine Biological Laboratory.

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Flasks of blue blood collected from horseshoe crabs. The white layer in the flask on the right shows amebocytes settling from the blood plasma.

mammalian plasma) the horseshoe crab’s blue plasma did not clot. The clotting factor, whatever it was, resided in the amebocytes.

Levin also discovered, to his dismay, that the clotting process was remarkably robust. In all of his early experiments, blood extracted from the crabs clotted spontaneously. Levin tried every anti-coagulant treatment, but nothing prevented the blood from clotting (9).

Finally, as a last resort, he made use of his studies in Conley’s laboratory, where he had seen rabbit blood coagulate after exposure to bacterial endotoxins.

Bacterial endotoxins survive the standard wet sterilization procedure that kills bacteria. Levin thought perhaps endotoxin contamination of his laboratory equipment was causing the persistent blood clotting.

To test his theory, he baked all of his glassware with sustained dry heat (the only way to ensure inactivation of endotoxins) and found that blood extracted and placed in his heat-treated glassware did not clot. Subsequently, he conducted all of his experiments with glassware that had been rigorously decontaminated in a drying oven at 180-190°C for over 2 h. In addition, he used only distilled water and other solutions that had been certified as endotoxin-free for human use (9).

Other than those precautions, though, Levin worked under Spartan conditions. Despite its stellar reputation, Woods Hole operated like a summer camp. One cold water spigot served the whole lab. For hot water, they boiled it over a gas flame.

91 Open windows provided the only air conditioning and ventilation, and Levin conducted all of his experiments bare-handed. Other workers routinely carted fresh marine specimens in and out for their experiments. There was no fume hood, and Levin’s use of N-ethyl-maleimide (a potent eye irritant he needed to prepare his amebocytes and prevent them from clumping) annoyed his lab mates and discouraged visitors.

Despite the makeshift environment, Levin succeeded in controlling all of his subsequent experiments, thanks to the baked glassware and

significantly to the marine ecosystem. Horseshoe crabs are a predator of mollusks and marine worms, and their eggs provide a food source for shorebirds, fish, and crustaceans (13, 14). They also churn and aerate ocean sediments, which facilitates oxygenation of the estuaries and marine food production (15).

Somehow, horseshoe crabs have adjusted to life in a bacterial soup in which 95% of the singlecell organisms are Gram-negative bacteria (6).

Crabs lack an immune system and cannot produce antibodies, but they have developed simple, efficient mechanisms for fending off environmental threats (5). The amebocytes in their blood serve many of the same functions as white blood cells in mammals.

Amebocytes engulf foreign or dead cells, transport and store digested materials, and repair wound sites, among other things (16).

The horseshoe crab’s rudimentary circulatory system is highly functional. Rather than an extensive network of arteries, veins, and capillaries, it is characterized by large sinuses that allow direct

careful laboratory technique. “My most valuable laboratory instrument was that drying oven” (9).

Levin and Bang reported their initial findings in 1964. They demonstrated that the amebocyte is necessary for clotting horseshoe crab blood. The clotting factors are located in the granules of the amebocytes and not in the blood plasma. And the gelclot reaction occurs when those clotting factors are exposed to bacterial endotoxins (11, 12).

Endotoxins are lipopolysaccharides, which are found in the outermost cell wall layer of Gram-negative bacteria. Little bits of lipopolysaccharides break off as the bacteria move in their environment. When the bacteria are killed or crushed, they release larger amounts. Levin’s results were consistent with Bang’s earlier observation that horseshoe crab blood clotted when exposed to dead Gram-negative bacteria. Bang had also observed that Gram-positive bacteria do not induce a clotting reaction (1). (The cell walls of Grampositive bacteria do not contain lipopolysaccharides.)

In the Public Domain

Horseshoe crabs are a resilient species. They can trace their ancestry back more than 400 million years to the Paleozoic era—before humans, before the dinosaurs, and even before flowering plants.

Surviving in the Bacterial Soup Horseshoe crabs are a resilient species. They can trace their ancestry back more than 400 million years to the Paleozoic era—before humans, before the dinosaurs, and even before flowering plants.

Along the Atlantic and Gulf coasts, they contribute

A view of the horseshoe crab’s anatomy

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contact of blood with the crab’s internal tissues.

However, these sinuses also give bacteria easy and extensive access to internal organs if the crab is wounded or its helmet-shaped shell is cracked.

Fortunately, over the eons, the horseshoe crab has developed an exquisitely sensitive mechanism for detecting endotoxin and combatting invasion by even minute amounts of bacteria.

In response to a bacterial threat, amebocytes release their granules and liberate clotting proteins. A gel forms to trap and prevent further entry of bacteria at the trauma point, as well as block the leakage of blood.

Other antimicrobial substances (such as tachyplesins and big defensins) are also released by the amebocytes and liquidate the trapped microbes (17).

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Photomicrograph of amebocytes from a horseshoe crab. Each ovoid cell is packed with granules.

Reducing to Practice

Jack Levin

Levin and Bang developed methods for extracting and isolating the clotting factors from the amebocyte granules (12, 18). A needle is inserted in the crab’s cardiac chamber from the dorsal side, and the blue blood is collected. After centrifuging, the blue supernatant fluid is discarded and the packed amebocytes are washed with saline. The cells are then osmotically lysed by adding distilled water, releasing the substances responsible for gel formation. The cellular debris is removed by centrifugation and the supernatant lysate is stored.

The resulting protein mixture was named Limulus amebocyte lysate, or LAL, a very descriptive moniker

comprised of the generic name of the horseshoe crab (Limulus), the blood cell that contains the clotting substances (amebocyte), and the process Levin and Bang used to harvest them (lysis).

The horseshoe crab is not the only species whose blood will clot in the presence of Gram-negative bacteria or their endotoxins. Investigators observed the same clotting mechanism in lobsters, oysters, and even some insects, but blood extraction from those animals was challenging (7). Levin found horseshoe crabs ideal: they are large, have a large blood volume, and have only one type of blood cell, from which the clotting substances can be easily extracted (9).

Levin was the first to use LAL in an assay for detecting bacterial endotoxins (19). A small amount of LAL was mixed with a sample solution in a test tube (18). If endotoxin was present in the sample, the solution gelled and stuck to the bottom of the tube when inverted. Although the rate of gel formation can be used to determine endotoxin concentration, more recent quantitative methods using photometric and turbidimetric endpoints have also been developed and certified by the US Pharmacopeia (20).

LAL Lift-Off

LAL test. Test tubes on the left are control samples of LAL; on the right, endotoxin has been added. The upper panel shows gel formation. The lower panel shows flocculent that forms early in the clotting reaction or in samples containing low concentrations of endotoxin.

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Across Eel Pond from the Marine Biological Laboratory where Levin and Bang were conducting their experiments, Stanley Watson, a microbiologist at the Woods Hole Oceanographic Institution, was studying the role of bacteria in the marine nitrogen cycle. He had isolated membrane fractions from some Gram-negative marine bacteria and was looking for a way to assess the purity of his samples (21).

93 A colleague told him about LAL, which Levin and Bang had recently isolated at MBL. Commercial sources of LAL were not available, so Watson obtained horseshoe crabs from the MBL Supply Department and set up production in his garage (9, 21). Unfortunately, his first batches were not sensitive enough for his purposes (21).

Watson decided to “spend a few weeks” trying to improve the sensitivity and reproducibility of his LAL batches (21). The weeks turned into months and a major research effort. Ultimately, he succeeded.

Watson’s LAL could reliably detect as little as 10-12 g of endotoxin (22). He not only produced LAL for his own research but also shared excess samples with other scientists who were studying bacterial endotoxins (5). When demand outpaced supply, he patented his procedure, set up a small company (Associates of Cape Cod, Inc.), and produced LAL as a lyophilized product (22).

Protecting Patients All Gram-negative bacteria, including Pseudomonas, Salmonella, and Escherichia, release endotoxin fragments from their cell walls. The immune systems of healthy people routinely handle these microorganisms when ingested, but in the bloodstream, as little as 10-6 g of endotoxin can cause endotoxemia: a high fever, organ failure, and possibly septic shock (22, 23). Endotoxin contamination is the most common cause of fever induced by intravenous drugs and fluids, blood products, and disposable pharmaceutical devices (24, 25).

Since the 1940s, pharmaceutical manufacturers had relied on the rabbit Pyrogen Test for detecting endotoxins in injectable drugs because, like humans, rabbits exhibit a pyrogenic response to endotoxin exposure. In the Pyrogen Test, rabbits are injected with a small amount of solution from a sterile drug batch. If the animals develop a fever, the batch is considered pyrogenic and is rejected. The Pyrogen Test and a test for sterility became the two most important tools in parenteral drug manufacturing (5).

Unfortunately, the Pyrogen Test has inherent disadvantages. It is time-consuming, expensive, and nonspecific. Also, the method produces results that are only qualitative, and the induced fever varies between animals due to differences in animal handling and interlaboratory factors. Some critics raised concerns about excessive use of animals.

Regulatory officials still accept the Pyrogen Test as a method for detecting bacterial endotoxin, but they were willing to consider alternatives. Legionnaires Disease provided a compelling argument in favor of LAL use. The endotoxin of the Legionnaires’ bacillus has a different spectrum of toxicity than other, more common, Gram-negative bacteria. It induces only a weak pyrogenic response in rabbits, but it is readily detected by LAL—1000-fold greater sensitivity (24).

Regulatory officials saw the LAL test as a simple, reproducible, inexpensive, and highly sensitive alternative to the Pyrogen Test. Also, LAL could be used to assay for endotoxin in products (such as radiopharmaceuticals, cancer chemotherapy agents, vaccines, and intrathecal drugs) that are not amenable to testing in rabbits (24, 25).

The Food and Drug Administration’s Office of Biologics established a reference standard for use in determining the sensitivity of each batch of LAL, and quantitation of endotoxin was defined in “Endotoxin Units” (7, 18, 20). In 1973, the FDA published the first guidelines for the manufacture of LAL (26). In 1977, Associates of Cape Cod received the first commercial license from the FDA to manufacture LAL for use in pharmaceutical assays (5, 27).

Also in 1977, the FDA issued the first in a series of guidance documents regarding validation and use of LAL to detect endotoxins in medical products, and regulatory officials began accepting data from the LAL test as an alternative to the Pyrogen Test (5, 24, 27).

In parallel, the US Pharmacopeia issued a series of monographs that established specific limits for bacterial endotoxin contamination in various parenteral products (e.g., intravenous drugs, intrathecal drugs, sterile water for injection, and radiopharmaceuticals) (20, 24).

Some manufacturers were reluctant to employ LAL because it was “too sensitive,” but most of them readily adopted LAL as their preferred quality control method for parenteral drugs (24). Unlike the Pyrogen Test, which (for practical reasons) was only used to assess the end product, LAL tests could be applied across the entire manufacturing process of both the drug substance and formulated product (7). This series of quality control tests was especially beneficial for biological drugs, which are expensive to produce.

Rejecting an entire lot of finished biological product was much more costly than detecting and addressing contamination at earlier stages of production.

Virtually all intravenous drugs, as well as in-process materials (i.e., containers and closures, sterile water,

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Biosketch:

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 be exploring a story about the “sleepy” sickness, Oliver Sacks, and the early days of L-DOPA. Don’t miss the exciting September 2015 issue.

bulk drug materials, and excipients), must now pass these multiple LAL checkpoints before marketing (7). In addition, the needles and tubing used to deliver those drugs, as well as implantable devices (e.g., pacemakers) and artificial kidneys used for renal dialysis, are also checked for endotoxins using the LAL test (5).

LAL has some limitations. It cannot distinguish between live and dead bacteria, nor differentiate between species of bacteria-generated endotoxins.

Fungi, as well as endotoxins, will elicit the clotting reaction. Still, the LAL test has been widely used not only for quality control of injectable drugs but also in many other situations. It is a handy method for rapid diagnosis of urinary tract infections and spinal meningitis. Other analysts have used LAL to assess food spoilage (fish, milk, and ground beef), as well as air and water quality (5).

In recognition of Frederik Bang’s insightful research and its healthcare impact, the International Endotoxin and Innate Immunity Society and the Stanley Watson Foundation established the Frederik Bang Award in 1985. The biennial award recognizes scientists for lifetime achievements in endotoxin research.

LAL on an Industrial Scale From one sick crab, a new industry emerged based on Bang and Levin’s discoveries. Specialist facilities in the United States, Japan, and China (including Associates of Cape Cod, Charles River, Lonza, Wako Chemicals, and Hyglos) now produce LAL commercially. They collect 600,000 horseshoe crabs each year and harvest the blood, which is worth $60,000 per gallon (5, 28).

Along the eastern coast of the United States, horseshoe crabs are caught in the spring when they swim into very shallow water to spawn. Although industrial-scale production of LAL has been streamlined, the method remains essentially the same as that first described by Levin and Bang.

Technicians extract no more than 30% of

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each crab’s blood, and the animals are then released back into the sea.

Studies have shown that the horseshoe crab’s blood volume rebounds in about a week. Hemocyanin takes more than 6 weeks to recover, and the blood cell count returns to normal in about 2-3 months (5, 13). Theoretically, horseshoe crabs could be bled several times a year, but the New England LAL manufacturers collect them only once a year. This restricted bleeding schedule allows the animals to recover, and they may be recaptured and bled again in subsequent years.

From one sick crab, a new industry emerged based on Bang and Levin’s discoveries.

When released, the horseshoe crabs return to their natural spawning areas, but the impact of biomedical bleeding on spawning productivity is unknown. Recent studies have shown that horseshoe crabs are more lethargic, slower, and less likely to follow the tides for several weeks after being bled (13). The bleeding and catch-and-release procedures result in an estimated 8-15% mortality in males and 1029% mortality in females (13).

Commercial harvesting of horseshoe crabs by fisheries (for bait) and by the biomedical industry (for LAL) is closely monitored and regulated in the United States (15). Of particular concern are decreases in the proportion of spawning females (from 30% to 10%) and in the number of eggs deposited in spawning beaches (13, 14). Research conducted by the US Geological Survey along the Atlantic and Gulf coasts suggested that multiple factors are likely responsible for these declines, including overharvesting of the crabs for fishing bait (a preferred bait for eels and predatory mollusks) and perhaps climate change (29).

Off the shores of Cape Cod where biomedical harvesting is concentrated, bait fishing has not been allowed since

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The clotting cascade in LAL. Bacterial endotoxins activate Factor C, which in turn activates Factor B. Similarly, fungal glucans activate Factor G. When activated by either Factor B’ or Factor G’, the clotting enzyme is activated, resulting in cleavage of coagulogen to produce coagulin.

2000 (5). Yet, despite the catch-and-release practices of LAL manufacturers, the loss of horseshoe crabs in this area, especially females, has been a growing concern (15). The Massachusetts Division of Marine Fisheries examined the factors contributing to horseshoe crab mortality resulting from biomedical bleeding. Based on the results of these studies, LAL manufacturers implemented gentler handling procedures in 2009, aimed at restoring the horseshoe crab population (15).

Synthetic Alternatives The declining horseshoe crab population poses a serious threat to both the marine ecosystem and pharmaceutical manufacturers who rely on the LAL test for quality control. Consequently, researchers have been exploring endotoxin detection alternatives that are not dependent on extraction of LAL from horseshoe crab blood.

Levin and his colleagues proved that the reaction between endotoxin and LAL was enzymatic and described essentially all of the endpoints that are currently in use (30, 31). They also isolated, partially purified, and described coagulogen, the gel-producing protein in LAL (31). Subsequent researchers identified five LAL proteins that are involved in clot formation.

The first four proteins in the clotting cascade (Factors C, B, G, and proclotting enzyme) are serine proteinase pro-enzymes. The final substance is coagulogen, a

soluble protein that is cleaved to produce coagulin, an insoluble gel (17).

Factor C is highly sensitive for detecting the lipopolysaccharides found in the cell walls of Gramnegative bacteria, whereas Factor G is highly sensitive to the (1,3)--glucan present in the cell walls of fungi.

Invading pathogens trigger activation of these factors, resulting in the sequential activation of Factor B and the proclotting enzyme. In the final step of this cascade, the activated clotting enzyme converts coagulogen to coagulin (17).

Several research groups have devised assays using recombinant Factor C. The rFC reagent has been designed to activate a fluorogenic substrate in the presence of endotoxin and produce a fluorescent product. Commercial kits utilizing recombinant Factor C are available from Lonza (PyroGeneTM) and Hyglos (EndoZyme® rFC). Unlike LAL, which is activated by both the lipopolysaccharides of Gramnegative bacteria and the glucans from fungi, the rFC fluorescence assays are selective for bacterial endotoxins.

While the rFC assays provide researchers with a valuable tool for endotoxin detection in laboratory research, pharmaceutical manufacturers still rely almost exclusively on the LAL test. The FDA permits the use of alternative endotoxin assays if the methods have been validated according to US Pharmacopeia compendial procedures (20, 27). But compendial validation is a long and challenging process, compared to the already-accepted LAL standard (5, 7).

Consequently, the lowly horseshoe crab, with its helmet-shaped shell, prehistoric ancestry, and blue blood, remains the sole sentry protecting millions of patients from otherwise deadly endotoxincontaminated drugs.

Koch’s Postulates • The bacteria must be present in every case of the disease.

• The bacteria must be isolated from the host with the disease and grown in pure culture.

• A pure culture of the bacteria causes the specific disease when it is inoculated into a healthy susceptible host.

• The bacteria must be recoverable from the experimentally infected host.

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References 1. Bang F (1956) A bacterial disease of Limulus polyphemus. Bull Johns Hopkins Hosp 98(5):325-351.

2. Howell WH (1885) Observations upon the chemical composition and coagulation of the blood of Limulus polyphemus, Callinectes hastatus, and Cucumaria sp. Johns Hopkins Univ Circulars 5(43):4-5.

3. Loeb L (1927) Amoeboid movement and agglutination of amoebocytes of limulus and the relation of these processes to tissue formation and thrombosis. Protoplasma 2(1):512-553.

4. Loeb L (1928) Amoebocyte tissue and amoeboid movement.

Protoplasma 4(1):596-625.

5. ERDG (2009) The Horseshoe Crab: How does the horseshoe crab protect the public health? available from: horseshoecrab. org/med/med.html 6. Watson SW, Novitsky TJ, Quinby HL, and Valois FW (1977) Determination of bacterial number and biomass in the marine environment. Appl Environ Microbiol 33(4):940-946.

7. Williams KL (2007) Limulus amebocyte lysate discovery, mechanism, and application, in Endotoxins: Pyrogens, LAL Testing and Depyrogenation, 3rd ed (Williams KL ed) pp 191217, Informa Healthcare, New York.

8. Shirodkar MV, Warwick A, and Bang FB (1960) The in vitro reaction of Limulus amebocytes to bacteria. Biol Bull 118(2):324-337.

9. Levin J, personal communication.

10. Thomas L (1974) The Lives of a Cell: Notes of a Biology Watcher. Viking Press, New York.

11. Levin J and Bang FB (1964) The role of endotoxin in the extracellular coagulation of Limulus blood. Bull Johns Hopkins Hosp 115 265-274.

12. Levin J and Bang FB (1964) A description of cellular coagulation in the Limulus. Bull Johns Hopkins Hosp 115:337345.

13. Anderson RL, Watson WH, and Chabot CC (2013) Sublethal behavioral and physiological effects of the biomedical bleeding process on the American horseshoe crab, Limulus polyphemus.

Biol Bull 225:137-151.

14. Morris, W (August 22, 2014) Will a shorebird knot up bacterial endotoxin assay supplies? PDA Letter; available from: www.pda.org/publications/pda-publications/pda-letter/ latest-news/2014/08/22/will-a-shorebird-knot-up-bacterialendotoxin-assay-supplies15. Leschen AS and Correia SJ (2010) Mortality in female horseshoe crabs (Limulus polyphemus) from biomedical bleeding and handling: implications for fisheries management.

Marine and Freshwater Behavior and Physiology 43(2):135-147.

16. Marine Biological Laboratory. The horseshoe crab: Blue blood; available from: hermes.mbl.edu/marine_org/images/animals/ Limulus/blood/bang.html

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17. Bergner A, Oganessyan V, Muta T, Iwanaga S, Typke D, Huber R, and Bode W (1996) Crystal structure of coagulogen, the clotting protein from horseshoe crab: a structural homologue of nerve growth factor. EMBO J 15(24):6789-6797.

18. Jorgensen JH and Smith RF (1973) Preparation, sensitivity, and specificity of Limulus lysate for endotoxin assay. Appl Microbiol 26(1):43-48.

19. Levin J, Tomasulo PA, and Oser RS (1970) Detection of endotoxin in human blood and demonstration of an inhibitor. J Lab Clin Med 75:903-911.

20. US Pharmacopeial Convention (2011) Chapter <85>, Bacterial Endotoxins Test; available from: www.usp.org/sites/default/ files/usp_pdf/EN/USPNF/revisions/m98830-bacterial_ endotoxins_test.pdf.

21. Watson SW and Novitsky TJ (1991) Determination of bacterial number and biomass in the marine-environment by Watson, SW, Novitsky, TJ, Quinby, HL, and Valois, VW. Current Contents/ Agriculture Biology & Environmental Sciences 50:10.

22. Sullivan JD and Watson SW (1978) Limulus lysate of improved sensitivity and preparing the same. US patent 4,107,077. 1978 Aug 15.

23. Beers MH, Porter RS, Jones TV, Kaplan JL, and Berkwits M,editors (2006) The Merck Manual of Diagnosis and Therapy.

Merck Research Laboratories, Whitehouse Station, New Jersey.

24. FDA (March 20, 1985) Inspection Technical Guides: Bacterial endotoxins/pyrogens, no. 40; available from: www.fda.gov/ICECI/Inspections/InspectionGuides/ InspectionTechnicalGuides/ucm072918.htm.

25. Blechová R and Pivodová D (2001) Limulus amebocyte lysate (LAL) test–an alternative method for detection of bacterial endotoxins. Acta Vet Brno 70:291-296.

26. FDA (Sept. 18, 1973) Limulus amebocyte lysate: additional standards. Federal Register 38(180):26103-26132.

27. FDA (June 2012) Guidance for industry pyrogen and endotoxins testing: questions and answers; available from: www.fda. gov/Drugs/GuidanceComplianceRegulatoryInformation/ Guidances/ucm314718.htm.

28. Monks K (Sept 4, 2014) Why this crab’s blood could save your life. CNN; available from: www.cnn.com/2014/09/04/health/ this-crabs-blood-could-save-your-life/index.html.

29. Faurby S, King TL, Obst M, Hallerman EM, Pertoldi C, and Funch P (2010) Population dynamics of American horseshoe crabs—historic climatic events and recent anthropogenic pressures. Molec Ecol 19:3088-3100.

30. Levin J and Bang FB (1968) Clottable protein in Limulus: its localization and kinetics of its coagulation by endotoxin.

Thromb Diath Haemorrh 19:186-197.

31. Young NS, Levin, J, and Prendergast RA (1972) An invertebrate coagulation system activated by endotoxin: evidence for enzymatic mediation. J Clin Invest 51:1790-1797.

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Science Policy

NIH FY 2016 Funding Now in Appropriators’ Hands Final Spending Numbers Depend on Congress’ Lifting of Budget Caps As the weather gets hotter in Washington so too will the budget battles facing Congress as it continues to move forward to pass spending bills funding the NIH and other federal agencies and programs.

Last May found Congress in an unusual position, having passed the first joint budget resolution in over five years. After a lot of selfcongratulations by members of congress over passing what should be an annual event, Congress must now turn to a far more important—and problematic issue— such as drafting and approving real appropriations bills funding government agencies for FY 2016.

Despite Congress’ genuflecting over passing the budget resolution, the bill is merely a guide to spending and has no force of law. The budget resolution offers suggested spending levels, but the Appropriations Committees will have their say at the end of the day—even if that day might not come until or after FY 2016 begins on October 1. But the budget resolution does reveal the political fault lines in Congress and the difficulty of finding a compromise on spending that allows for growing the NIH and other federal agencies.

For instance, the budget resolution keeps sequestration in place, continuing the squeeze on non-defense discretionary programs while increasing defense spending by more than $40 billion in an account not subject to the

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2011 Budget Control Act spending caps. Senator Patty Murray (D-WA), whose leadership helped provide for some sequestration relief during the past two years criticized the budget agreement stating, “Instead of working with us to build on the bipartisan budget deal we struck last Congress, Republicans have introduced a budget that would lock in sequestration, hollow out defense and non-defense investments, and use gimmicks and games to paper over the problems.” Murray’s comments also reveal the very real policy fractures between Republicans and Democrats that will play out through the remainder of this summer and into fall. President Obama has stated that he would veto any funding bill that retains sequestration levels of funding. Office of Management and Budget (OMB) Director Shaun Donovan stated that the president “has been clear that he is not willing to lock in sequestration going forward, nor will he accept fixes to defense without also fixing non-defense.”

Political Compromise Necessary Even some Republicans admitted that passing spending bills that fall within the budget resolution guidelines will almost certainly never happen. Their strategy, according to Senate Majority Leader Mitch McConnell (R-KY) is “To try to delay, reign in, and restrict various bureaucratic overreach through the appropriation bills that spend the money.” The House has a large enough Republican majority to pass spending bills that more closely align with the budget resolution. However, even in the House that is not a given. House Appropriation Committee Chair Hal Rogers (R-KY) has stated that there likely will not be enough votes in his committee to approve appropriations spending levels that are already too low. However, the Senate will need Democrats to pass spending bills, and that will not happen unless the spending caps are lifted for both non-defense discretionary spending and defense spending.

Several weeks before the budget resolution was approved, the House Appropriations Committee approved its subcommittee allocations for FY 2016. Not surprisingly, the total allocation

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follows the discretionary (non-defense and defense spending) $1.017 trillion spending cap mandated by the 2011 Budget Control Act, as well as adopted in the FY 2016 budget resolution. The House allocation for the Labor-HHS-Education subcommittee (the subcommittee that funds NIH) is $153.05 billion. This is a decrease of $3.7 billion (2.4 %) from the current year’s level. The research community recommended funding levels of at least $163.6 billion—the level it was in FY 2010. The FY 2016 spending allocations essentially prevent any chance of the NIH, or any other program, of receiving a modest increase.

Even if the NIH were to receive inflation increases, it would mean more sizeable cuts to other worthy programs. How or whether the Labor/ HHS subcommittee makes these programmatic spending decisions remains to be seen, as Chairman Rogers has indicated. The Committee’s Ranking Democrat, Nita Lowey (D-NY) offered an amendment to increase the allocations to the Appropriations Committee by $75 billion that would have brought the total allocation to the spending levels in the President’s FY 2016 budget. But that effort was rejected along a party line vote. And Rep. Duncan Hunter (R-CA) told the San Diego Union-Times that, “As Congress prioritizes spending under federal budget caps, one area that deserves a bigger slice of pie is NIH, which leads in medical advancement and innovation, there are plenty of things that should see less funding, but NIH isn’t one of them.”

At press time, the Senate had not approved its subcommittee allocations.

The House allocation for the LaborHHS-Education subcommittee (the subcommittee that funds NIH) is $153.05 billion. This is a decrease of $3.7 billion (2.4 %) from the current year’s level.

Given the comments mentioned above by Appropriations Chairman Rogers, Rep. Hunter, and the efforts of Rep. Lowey, there appears to

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be some momentum to “fix” sequestration, lifting the budget caps to allow agencies like the NIH to begin the process of restoring funding that was lost in the past decade. How to get there is both the question and the problem. Congressional leadership has said they hope to fast track appropriations bills and finish well before the current fiscal years ends on September 30. That might be a pipe dream and at a minimum is probably too much to hope for. More likely, as we get closer to the end of this fiscal year, we will hear, once again, talk of shutdowns and the increased likelihood of continuing resolutions to fund the government beyond the start of the new fiscal year on October 1. What remains clear and certain is the need for ASPET members to continue to reach out to their Congressional delegation

during this process, reinforcing the need for steady and sustained increases for the NIH to help meet the many scientific opportunities that will never be fulfilled under current funding levels.

What remains clear and certain is the need for ASPET members to continue to reach out to their Congressional delegation during this process, reinforcing the need for steady and sustained increases for the NIH to help meet the many scientific opportunities that will never be fulfilled under current funding levels.

Written Testimony of the American Society for Pharmacology & Experimental Therapeutics Submitted to the House and Senate Appropriations Subcommittee on Labor, Health and Human Services, Education & Related Agencies Fiscal Year 2016 Appropriations for the National Institutes of Health The American Society for Pharmacology and Experimental Therapeutics (ASPET) is pleased to submit written testimony in support of the National Institutes of Health (NIH) FY 2016 budget. ASPET recommends a FY 2016 NIH budget of at least $32 billion.

Steady and sustained investment in the NIH is critical to improving human health, stimulating state and local economies, and improving the nation’s global competitiveness. We call upon Congress to ensure that the NIH remains a national priority.

ASPET appreciates Congressional action in providing NIH-needed increases in the FY 2014 and FY 2015 omnibus appropriations bills. However, these increases did not restore the purchasing power lost to sequestration in FY 2013. From 2003-2013, the NIH budget failed to keep pace with inflation in

research costs leading to nearly a 25% reduction in the agency’s purchasing power and a 34% reduction in the primary grant mechanism for supporting investigator-initiated research. A FY 2016 budget of $32 billion would enable the NIH to fund 465 more research grants and help restore the agency’s lost purchasing power that has occurred over the past decade.

Additionally, 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. Not only are jobs increasingly limited in the academic sector, but the health industry too is under significant stress. The “brain drain” of young scientific talent jeopardizes the nation’s leadership in biomedical research. A 2013 survey of ASPET’s own

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graduate students and post-doctoral researchers 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 United States to pursue a career in biomedical research.

A $32 billion budget for the NIH in FY 2016 is an important start to help restore NIH’s biomedical research capacity. Currently, the NIH only can fund one in six grant applications, the lowest rate in the agency’s history. Many highly innovative proposals that have important implications for human health go unfunded as a consequence of limited NIH funding.

A budget of at least $32 billion in FY 2016 will help the agency manage its research portfolio more effectively without having to withhold funding for existing grants to researchers throughout the country.

Only through steady, sustained, and predictable funding increases can the NIH continue to fund the highest quality biomedical research to help improve the health of all Americans and continue to make significant economic impact in many communities across the country.

There is no substitute for a steady, sustained federal investment in biomedical research. Industry, venture capital, and private philanthropy can supplement some elements of health research, but they cannot replace the investment in basic, fundamental biomedical research provided by the NIH. Neither the private sector nor industry will be able to fill a void for NIH-funded basic biomedical research. Much of the research undertaken by industry builds upon the discoveries generated from NIH-funded projects. The majority of the investment in basic biomedical research that NIH provides is broad and long-term, providing a continuous development platform for industry, which would not typically invest in research that may be of higher risk and require several years to fully mature. In addition to this long-term view, the NIH also has mechanisms in place to rapidly build upon key technologies and discoveries that have the ability to have significant impact on the health and well-being of our citizens.

Many of the basic science initiatives supported by the NIH have led to totally unexpected discoveries and insight that have transformed our mechanistic

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understanding of and our ability to treat a wide range of diseases.

Diminished Support for NIH Will Negatively Impact Human Health Additional cuts or limited growth in the NIH budget will further reduce the NIH’s purchasing power and accelerate the loss of scientific opportunities to discover new therapeutic targets. Without a steady, sustained federal investment in fundamental biomedical research, scientific progress will be slower, and potentially helpful diagnostic methods, therapies or cures will not be developed. For example, more research is needed on Parkinson’s disease to help identify the causes of the disease and help develop better therapies. As another example, discovery of gene variations in age-related macular degeneration could result in new screening tests and preventive therapies. More basic research is needed to focus on new molecular targets to improve treatment for Alzheimer’s disease. As yet another example, diminished support for NIH will prevent new and ongoing investigations into rare diseases that the Food and Drug Administration estimates almost 90% are serious or life-threatening.

Historically, our past investment in basic biological research has led to many innovative medicines. The National Research Council reported that of the 21 drugs with the highest therapeutic impact, only five were developed without input from the public sector. The significant past investment in the NIH has provided major gains in our knowledge of the human genome, resulting in the promise of pharmacogenomics and a reduction in adverse drug reactions that currently represent a major worldwide health concern. The NIH is the world leader in efforts to prevent and treat HIV-AIDS. Several completed human genome sequence analyses have pinpointed disease-causing variants that have led to improved therapy and cures, 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 medicine” or precision medicine and its application to a wide range of clinical disorders requires research to identify and test optimal diagnostic and therapeutic approaches for each individual. Our past support for the NIH has

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revealed new frontiers of immunopharmacology and regenerative medicine which are producing cost savings by reducing in-patient hospital care for debilitative autoimmune diseases like rheumatoid arthritis and restoring movement and function through regenerative interventions. Furthermore, the NIH must continue its support of research to prevent and treat infectious diseases.

Investing in the NIH Helps America Compete Economically A $32 billion budget in FY 2016 will also help the NIH train the next generation of scientists and provide a platform for broader workforce development that is so critical to our nation’s growth. While most NIH trainees follow a career path in research, many individuals trained in the sciences through NIH support become educators in high schools and colleges. These individuals also enter into other areas of technology development and evaluation in the public and private sectors, further enriching the community and accelerating economic development.

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. One national study by an economic consulting firm found that federal (and state) funded research at the nation’s medical schools and hospitals supported almost 300,000 jobs and added nearly $45 billion to the U.S. economy. NIH funding also provides the most significant scientific innovations of the pharmaceutical and biotechnology industries.

Thus, this investment will help to create jobs and promote economic growth. A stagnating NIH budget will mean forfeiting future discoveries and jobs to other countries.

It is a sobering fact that the US share of global research and development investment from 1999–2009 was only 31%, representing a decline of 18%. In contrast, other nations continue to invest

aggressively in science. 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 prioritize their budgets accordingly.

Conclusion ASPET appreciates the many competing and important spending decisions the Subcommittee must make. However, the NIH’s contribution to the nation’s economic well-being and to the health of our citizens should make it one of the nation’s top priorities. Lawmakers must replace sequestration in 2016 and beyond with a bipartisan, balanced approach to deficit reduction so that vital investments can be made in the best interests of the nation.

With enhanced and sustained funding, the NIH can begin to reverse its decline and help achieve its potential to address many of the more promising scientific opportunities that currently challenge medicine and affect health care in our country. A budget of at least $32 billion in FY 2016 will be a good first step in allowing the agency to begin moving forward to full program capacity, exploiting more scientific opportunities for investigation, and increasing investigators’ chances of discoveries that prevent, diagnose, and treat disease. The NIH should be restored to its place as a national treasure, one that attracts and retains the best and brightest to biomedical research and provides hope to millions of individuals afflicted with illness and disease.

ASPET is a 5,100 member professional society whose members conduct basic, translational, and clinical pharmacological research within the academic, industrial, and government sectors. Our members discover and develop new medicines and therapeutic agents that fight existing and emerging diseases, as well as increase our knowledge regarding how therapeutics can be used to improve human health.

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Susanna Aguirre Joins ASPET as Manager of Government Affairs and Science Policy Ms. Aguirre most recently served as Policy and Development Specialist at the American Medical Informatics Association (AMIA) and began working at ASPET on June 8th. She is a graduate of Randolph-Macon College and began her career as a Congressional staffer. Ms. Aguirre continued to build strong bipartisan relationships on the Hill through her advocacy and government relations work at other associations including the American Society of Plastic Surgeons and the American Association for Cancer Research. Ms. Aguirre is an active member of the Association of Government Relations Professionals, Women in Government Relations, and the American Society of Association Executives. With her background, experience, and enthusiasm, Ms. Aguirre is excited to jump into her role to further develop our Science Policy and Government Affairs programs.

ASPET Washington Fellows Visit Congress For the third consecutive year, ASPET’s Washington Fellows made their annual visits to Washington, DC to meet with their Congressional delegation. Since the program’s inaugural year in 2013, ASPET’s Fellows have educated lawmakers and effectively made the case for increased support for biomedical research and the need for steady and sustained support for the National Institutes of Health.

This spring, ASPET Fellows, comprised of ten graduate students, postdoctoral fellows, and junior faculty, visited 31 Congressional offices.

Some common themes emerged from these visits.

Perhaps most encouraging was that there seemed to be genuine awareness that the unstable funding situation over the past decade has impacted aspiring early-career scientists and this development has major implications for the future of America’s scientific workforce. Even among the most fiscally conservative Congressional offices visited there was acknowledgement that sustained funding for the NIH is important and their state does not want to see young people leave for other opportunities. However, this support was often qualified with comments

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that NIH-funded institutes could do a better job at exploiting public-private partnerships or that NIH funded research needs to be managed better.

Ben Lieblong of the University of Arkansas School of Medical Sciences following his meetings with Arkansas Representative French Hill and Senator Boozman. (Pictured here: Congressman French Hill)

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ASPET Fellows informed their Congressional delegation that their home institutions are under great stress, that pharmacology and other related departments are smaller than they were just a few years ago, and that it is frustrating to see other nations, even those imposing their own austerity measures,

Tamara Escajadillo

Benjamin J. Lieblong

University of California at San Diego

University of Arkansas for Medical Sciences

Andrew Merluzzi

Dhara Patel, PhD

University of Wisconsin - Madison

New York Medical College

investing robustly in biomedical research while in the United States we have cut funding by roughly 25% over the last decade. Fellows questioned the viability of their institutions and the countryâ&#x20AC;&#x2122;s biomedical research enterprise if the next decade is anything like the past ten years. A common point made was that

The ASPET Washington Fellows Program was a great opportunity to gain firsthand experience seeing how our government and legislature works. This opportunity gave me broader perspectives into not only the legislative process, but also insight Menglu Yuan into the complexity of lawmaking University of that navigates between conflicting California at Irvine interests on important issues within our country. After my Hill visit, I realized that it is extremely critical for scientists to speak to Congress about the importance of our work.

Compared to other interest groups, science and research is highly underrepresented on Capitol Hill. As researchers, we are our own best advocates, and it is our responsibility to communicate how our novel ideas and innovations keep this country strong. This not only applies to faculty or senior scientists but also graduate researchers and postdoctoral scholars, the cornerstones of the biomedical research community who have the most to lose when funding is cut.

Menglu Yuan University of California at Irvine

Phillip A. Saccone University of Michigan Medical School

Katherine M. Serafine, PhD University of Texas Health Science Center, San Antonio

Maria Briscione Emory University

Ed Stahl Scripps Research Institute (Florida)

Michael C. Tranter, PhD

After my Congressional visits, I realized that advocating for biomedical research is part of being a responsible scientist. As young scientists, we are in a position to provide a compelling, novel perspective about the devastating effects of NIH budget cuts and unpredictable funding, and we should utilize all opportunities to do so.

Maria Briscione Emory University

University of Cincinnati College of Medicine

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once labs close and jobs are lost, it is very difficult to bring that infrastructure and intellectual capital back home. This point may have resonated with some but certainly not all Congressional offices. Following her Congressional visits, Dhara Patel, a graduate student from the New York Medical College noted, “I assumed that people in Washington would have decent knowledge about NIH. It seems they do know the importance of federal funding to NIH, but they do not know how much it affects scientists in today’s time. They do have sympathy for NIH, but they do not know how many people lose jobs in academia due to less funding.” To help change that perception, Philip Saccone, a graduate student the University of Michigan Medical Center feels that effective advocacy requires a consistent effort for a relatively long period of time: “Advocates need to make an effort to build a relationship with members and their staff, and to be a resource for them on a particular issue. The political

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landscape is always shifting, and you never know where or when an opportunity will arise—it may appear in the most unlikely of circumstances and be delivered by the most unlikely people. Much like research, advocacy requires persistence and resilience. If you’re not involved, you can’t expect to have a seat at the table when something important comes up.”

Besides pounding the vast marble hallways of the various Congressional office buildings, each ASPET Fellow visited with a Washington-based science policy professional. The purpose of these visits is to give Fellows another perspective of how things get done in Washington, learn about another professional organization, and do a little information gathering for any possible interest to changing career paths.

ASPET would like to thank and acknowledge the commitment and great effort by the 2015 Washington Fellows for being great representatives of ASPET and advocates for biomedical research!

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2016 Washington Fellows Program Submit your application by September 2, 2015 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 2, 2015, 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 2016: ASPET Fellows will attend the 2016 ASPET Annual Meeting in San Diego and any related policy program sessions assigned. Fellows will receive an ASPET travel award to attend the meeting.

Application Information ASPET anticipates up to 10 Washington Fellows Program participants in 2016. 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 2, 2015, will not be considered.

For more info: www.aspet.org/2016_ASPET_Washington_Fellows_Program (301) 634-7060 publicaffairs@aspet.org

as pet.o rg

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Education News Future of Bioscience Graduate and Postdoctoral Training Meeting in Review An increasing number of national reports have highlighted problems in the current training paradigms for graduate students and postdoctoral researchers. While these issues affect all scientists, they are felt disproportionately by life scientists, who compose 65% of those holding postdoctoral positions1. As the number of postdoctoral life scientists continues to expand, career trajectories are rapidly shifting away from the historical trend of obtaining independent research or faculty positions. Approximately one-third of life sciences PhD recipients ultimately move into jobs unrelated to research2. Those who do obtain academic positions face a rapidly declining number of tenuretrack opportunities and are more likely to serve in contingent or adjunct roles with little job security.

1 2

Other commonly-cited concerns include low and stagnant wages for postdoctoral researchers, an increasing reliance on external funding to support trainees, and an increase in the amount of time spent in training positions1.

Although a number of possible policy and practice solutions to these issues have been proposed, there was still a need for a national conversation among a large, representative group of stakeholders to discuss these ideas in depth. In response to this need, a national summit on the Future of Bioscience Graduate and Postdoctoral Training was held May 3â&#x20AC;&#x201C;5, 2015 on the campus of the University of Michigan, Ann Arbor. Sponsored by the University of Michigan and the NIH-funded BEST (Broadening Experiences in Scientific Training) program at Wayne State University, the conference had broad representation from educators and administrators from universities and

National Academy of Sciences (2014) The Postdoctoral Experience Revisited. The National Academies Press, Washington, DC. National Institutes of Health (2012) Biomedical Research Workforce Working Group Report. Bethesda, MD.

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medical schools, postdoctoral offices, the National Postdoctoral Association, the National Institutes of Health, the National Science Foundation, the National Academies, FASEB, the private sector, and individuals who have invested effort over the years in addressing these issues. ASPETâ&#x20AC;&#x2122;s Education Manager, Catherine Fry, attended as a representative of the Society.

After several stage-setting plenary talks, the majority of the meeting was devoted to concurrent workshops on pressing issues related to: 1) experiential learning outside the university, 2) new models for training, 3) curricular reform, 4) career track options, 5) correcting gender and diversity imbalances, 6) funding models, and 7) assessing and balancing PhD supply and demand. Workshop participants were charged with developing consensus recommendations that would be developed into a white paper following the conference. Some highlights of these recommendations include incorporating direct exposure to a variety of career options into graduate training through experiential learning (e.g., internships, job shadowing, and service opportunities), incentivizing mentoring and professional development at all stages of training, and increasing the focus on transferrable

skills. Other suggestions included linking diversity training to accreditation and/or promotion and tenure requirements and requiring the reporting of trainee outcomes at the levels of both the laboratory and the university. Workshop participants stressed the need for more robust data on career outcomes, in particular for postdoctoral researchers, who are typically not tracked in the same manner as graduate students.

It is worth noting that recommendations related to mentoring, diversity, and experiential learning were closely aligned with two of ASPETâ&#x20AC;&#x2122;s ongoing BIG IDEAS projects: Pharmacology Industry Internships for PhD Students (PIIPS), and From Senior Mentor to Highly Skilled Career Coach: A Novel Approach to Breaking the Diversity Roadblock. The support and leadership provided by professional societies was identified as key to the success of recommendations put forward by this group. The conference served to help ASPET join a national conversation while also sharing information about our programs and priorities with the broader bioscience community. A follow-up conference is planned for 2016, and ASPET looks forward to continuing the dialogue about these important issues.

ASPET Names 2015 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 program aims to heighten interest in science as a career and to increase the number of young scientists entering the research discipline of pharmacology. ASPET offers both institutional and individual SURF awards. Institutions with funded fellowship programs are listed at: www.aspet.org/ awards/SURF/institutional-Funded/. 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 5 students selected for 2015 individual fellowships:

Tyler Hinshaw, a student at Wake Forest University, will conduct research with Dr. Rong Chen at the Wake Forest School of Medicine. Tyler will be working on projects related to posttranslational modification of dopamine D2 receptors and Tyler Hinshaw dopamine transporters following amphetamine self-administration in rodents. Her research aims to characterize amphetamine-induced ubiquitination of D2 receptors in rats in order to contribute to

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the understanding of mechanisms involved in psychostimulant addiction.

Vivek Medepalli, a student at the University of California – San Diego, will conduct research with Dr. Michael Rogawski at the University of California – Davis. Vivek’s research will focus on testing possible therapeutic agents for myotonia, which is a heritable ion channel Vivek Medepalli disorder that interferes with skeletal muscle relaxation.

He will be testing compounds within a library of Nav channel slow inactivation enhancers for antimyotonic efficacy using a combination of muscle myography and patch-clamp analyses.

Tyler Murphy, a student at Oglethorpe University, will conduct research in the lab of Dr. Kevin Murnane at Mercer University. Tyler’s research project will examine the role of serotonin receptors in thermoregulation under anesthesia and Tyler Murphy characterization of the brain systems involved in anesthesia-induced hypothermia. The ultimate goal is to improve patient outcomes by developing new medications that will directly improve thermoregulation.

Amelia Spaulding, a student at the Ohio State University College of Pharmacy, will conduct research with Dr. Dale Hoyt. Her project will assess roles for transcriptional cyclindependent kinases in Amelia Spaulding

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inflammatory gene expression. She will investigate whether the transcriptional cyclin-dependent kinases that are thought to regulate mRNA production also affect induction of cyclooxygenase-2 and inducible nitric oxide synthase. The results should indicate whether or not these kinases regulate expression of these inflammatory proteins and their mRNAs in endothelial cells.

Emily Warner, a student at the University of New England, will conduct research with Dr. Glenn Stevenson. Emily’s research will focus on the study of pain-depressed behaviors in rodents.

She will evaluate delta/ mu agonist interactions in Emily Warner an assay of osteoarthritis pain-depressed operant responding. Her work is designed to help address the limited effectiveness of currently available prescription opioids and the limited utility of traditional behavioral dependent measures.

We wish the 2015 individual Fellows as well as the Fellows participating in the SURF institutional programs a productive and fun summer of research!

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Postdoctoral Members: Share Your Feedback and Earn a Chance to Win an Amazon Gift Card!

The status and career outcomes of postdoctoral researchers have been the subject of an increasing number of national reports from the National Institutes of Health, the National Science Foundation, the National Academies, and others. Issues related to the career paths and training of life scientists were also the focal point of a recent conference on the Future of Bioscience Graduate and Postdoctoral Training (see page 104 ). Professional societies such as ASPET serve an important role in helping to better understand the career outcomes, professional development needs, and unique circumstances of the postdoctoral members they serve. To help us learn more about our postdoctoral members and their needs, we invite you to respond to this survey by July 15, 2015: www.surveymonkey.com/s/ASPETpostdocs15.

Your responses will help us identify ways to serve you better—we look forward to hearing from you!

As a thank you for sharing your views, two respondents will be chosen at random to win a $50 gift card from Amazon.

Carla Burns Joins ASPET as Program Coordinator Carla joins ASPET as program coordinator with several years of experience working with non-profit organizations. She will support ASPET’s education programs and will serve as a liaison to the 10 divisions. She first entered the field at Providence Hospital working alongside Gastroenterology and Hepatology research. Carla has a special interest in the effects of toxic substances on populations. Carla received her master’s degree in Environmental Science with a focus on ecotoxicology from American University and holds a bachelor’s degree in Earth and Environmental Science from the University of Rochester. Outside of work she enjoys running, learning new dance styles, and attempting to make recipes from around the world.

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Journal News ASPET Journals Support the NIH Principles and Guidelines for Reporting Preclinical Research Over the last several years there has been growing concern within the biomedical research community regarding a common perception that the level of scientific reproducibility and self-correction in preclinical research is not adequate (1). In one initiative to address this situation, the NIH in collaboration with Nature and Science/American Association for the Advancement of Science held a workshop on June 14, 2014 for biomedical journal editors (including the Journal of Pharmacology and Experimental Therapeutics) that addressed the reproducibility and rigor of published research findings. Workshop attendees provided input to a draft set of methodological guidelines for published research. The ASPET Board of Publications Trustees reviewed the draft guidelines and submitted a response to the NIH on August 19, 2014.

On November 5, 2014, the National Institutes of Health announced “Principles and Guidelines for Reporting Preclinical Research” (www.nih.gov/about/ reporting-preclinical-research.htm). The guidelines address five principle areas of concern for the publication of preclinical biological research: rigorous statistical analysis, transparency in reporting, data and material sharing, consideration of refutations, and the establishment of best practice guidelines in the areas of image-based data and the description of biological materials with enough information to uniquely identify the reagents (in particular, antibodies, cell lines, and animals).

ASPET publishes three primary research journals: The Journal of Pharmacology and Experimental Therapeutics (JPET, founded in 1909), Molecular Pharmacology (1965), and Drug Metabolism and Disposition (DMD, 1973). ASPET also publishes a

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review journal, Pharmacological Reviews, established in 1949. It is the intent and mission of ASPET’s journals to hold to high standards of scientific rigor.

Since their inception, ASPET’s primary research journals have placed no limit on the materials and methods section in each journal, allowing for detailed descriptions of experimental methodology. Critical evaluation of experimental design issues, statistical analyses, and the validation of reagents have also been key components of the peer-review process.

Peer reviewers are evaluated by the editors-in-chief and associate editors on their attention to these issues. In recent years, ASPET’s Board of Publications Trustees has expanded and strengthened its reporting requirements. For instance, the chemical identity of novel research compounds must be provided, the sex of experimental subjects must be noted for in vivo studies and studies using primary cultures of cells or tissues from animals or humans.

The coordinates and structure factor amplitudes for studies, including crystallographic data must be provided and deposited with the Protein Data Bank. The nomenclature used to identify receptors and ion channels should conform to the guidelines of the Committee on Receptor Nomenclature and Drug Classification of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), whose nomenclature reports are published in Pharmacological Reviews. Most recently, we eliminated limits on references.

Consistent with its history, ASPET strongly supports the NIH Principles and Guidelines for Reporting Preclinical Research. ASPET’s journals and over 70 other leading biomedical research journals have endorsed these guidelines (http://www.nih.gov/

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about/endorsing-jounals.htm). In order to further enhance support for the goals of the NIH Guidelines and provide a higher level of transparency in the areas of experimental design, description of methods, and statistical analysis, ASPET has implemented the following editorial actions: The DMD, JPET, and Molecular Pharmacology websites have been updated with revised Instructions to Authors establishing the preferred standards for reporting of experimental design and methodology and reporting requirements for randomization, blinding, normalization and statistical analyses, and reagent validation. Several excellent reviews, commentaries, and the references therein on key aspects of experimental design and statistical analysis have been recently published that authors and readers will find of value (2-4). The DMD, JPET, and Molecular Pharmacology Editorial Boards will carefully review how authors have addressed these methodological parameters during the peerreview process for all future submissions to the journal in an effort to further enhance the scientific rigor and transparency of pharmacological research reported in DMD, JPET, and Molecular Pharmacology. These changes were developed by the Board of Publications Trustees working with the editors of the ASPET journals. We know that you our readers and authors are proud to join us in this goal of increased research quality and transparency.

ASPET Board of Publications Trustees Mary Vore, Chair Darrell Abernethy Randy Hall Michael Jarvis Kathryn Meier Edward Morgan Kim Neve David Sibley Stephen Traynelis Jeffry Witkin Judy Siuciak, ex officio Rich Dodenhoff, Journals Director

References 1. Collins FS and Tabak LA (2104) NIH plans to enhance reproducibility Nature 505:612-613.

2. Landis SC, Amara SG, Asadullah K, Austin CP, Blumenstein R, Bradley EW, Crystal RG, Darnell RB, Ferrante RF, Fillit H, et al.

(2012) A call for transparent reporting to optimize the predictive value of preclinical research Nature 490:187-191.

3. Marino MJ (2014) The use and misuse of statistical methodologies in pharmaceutical research. Biochem Pharmacol 87:78-92.

4. Motulsky H (2014) Common misconceptions about data analysis and statistics J Pharmacol Exp Ther 315:200-205.

New Services ASPET is participating in the pilot program for an article rental service from Reprints Desk, a document delivery service that has partnered with ASPET since 2010. The rental service allows a user to read an article online but not download, save, or print it. The rental fee is lower than that to purchase the article through document delivery. Document delivery services have replaced some corporate libraries and are popular with companies that are too small to support a library. This new service is particularly attractive to users because they can identify articles to rent using their normal search tools such as PubMed and Google in conjunction with an easy-touse widget.

All content in ASPET’s journals that has a digital object identifier (DOI) is being indexed by the ReadCube Discover service. DOIs have been assigned to DMD, JPET, and Molecular Pharmacology articles since 2002; they were added to Pharmacological Reviews in 2003. ReadCube offers a suite of scholarly tools, and ASPET’s content will gain greater visibility by being discoverable through them. ReadCube provides web, desktop, and mobile platforms to its users.

Greater exposure to ASPET’s content through these services will benefit the publications program and the authors we support.

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Editorial Boards Eleven researchers recently joined the Molecular Pharmacology Editorial and Advisory Board. Dr. Stephen Traynelis, Editor, is pleased to welcome these new EAB members to the journal: Dr. Katerina Akassoglou, Univ. of California, San Francisco Dr. Carlos Barajas-López, Queen’s Univ. at Kingston Dr. Laura Bohn, The Scripps Res. Inst.

Dr. Mortiz Bunemann, Universitat Marburg Dr. Adolfo García-Sáinz, Univ. Nacional Autonoma de Mexico Dr. Silvio Gutkind, NIDCR, National Inst. of Health Dr. Hiroshi Itoh, Nara Inst. of Science and Technology

Dr. Ralf Jockers, INSERM Dr. Thomas Kash, Univ. of North Carolina Chapel Hill Dr. John Kehrl, NIAID, National Inst. of Health Dr. Gunnar Schulte, Karolinska Inst.

Drug Metabolism and Disposition recently added three members to its Editorial Advisory Board. Dr. Eddie Morgan, Editor, welcomes them to DMD: Dr. Aleksandra Galetin, Univ. of Manchester Dr. Hyunyoung Jeong, Univ. of Illinois at Chicago Dr. Chuan Li, Shanghai Inst. of Materia Medica, CAS ASPET’s Board of Publications Trustees appreciates the commitment of these researchers to the Society’s journals and is grateful for their service.

Molecular Pharmacology 50th Anniversary The July issue of Molecular Pharmacology celebrates the journal’s 50-year anniversary. This special issue includes minireviews and research articles from seven former and current editors plus a perspective written by the editors that provides a historical overview of the journal, emphasizing the substantial impact the journal has had on the field of pharmacology as well as on biomedical science.

In the special issue, William Caterall (editor 1986–1990) and Teresa Swanson discuss the structural basis of voltage-gated sodium channel function and their modulation by pharmacological probes and drugs. Eduardo Lazarowksi and Ken Harden (editor 1991–1994) review UDP-sugars as signaling molecules at purinergic receptors. Ray Dingledine (editor 1995–1999) and colleagues evaluate EP2 receptor signaling in microglia in

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the context of neuronal death. Olivia Yu and Joan Heller Brown (editor 2000–2002) review GPCR and RhoA-mediated control of transcription as it relates to inflammation, differentiation, and cell proliferation. Paul Insel (editor 2003–2005) and colleagues discuss novel endo-G protein coupled receptors as physiological regulators of therapeutic targets. Karen Gregory and Jeffrey Conn (editor 2006–2011) provide molecular insight into allosteric regulation of metabotropic glutamate receptors. Finally, Stephen Traynelis (editor 2012–present) and colleagues summarize the effects of human disease-associated mutations in both inhibitory GABAA receptors and excitatory glutamate receptor families.

These reviews cover a broad range of topics, emphasizing the breadth of topics the journal covers. True to its original goals, Molecular Pharmacology remains an outstanding venue for reporting work that provides a mechanistic understanding of drugs, molecular probes, and their biological targets.

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ASPET BIG IDEAS II Do you have a BIG IDEA for ASPET? Submit your proposal today!

Due to the tremendous success of the last BIG IDEAS Initiative, ASPET is once again asking members to put forward their best ideas for projects. The requirements for these projects are that they: Have broad appeal to ASPET membership Have long term positive impact on the discipline of pharmacology or on ASPET membership Are creative and transformative for ASPET Invest in the future of ASPET Subm bm your proposal by Submit S ep pt September 28, 2015!

For more information and to submit your BIG IDEA vi visit:

www.aspet.org/ASPET_BiG_Ideas_II June 2015 • The Pharmacologist

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New Members REGULAR MEMBERS Michio Asahi Osaka Med College, Japan Anjon Audhya Univ of Wisconsin-Madison Jamie J. Bernard Michigan State Univ Price Blair Lynchburg Coll, VA Heather Blanchette Cubist Pharmaceuticals, MA Donald K. Blumenthal Univ of Utah Gerda E. Breitwieser Geisinger Clinic, Weis Center for Research, PA Mira Chang Scripps Res Inst, FL Yu-Chung E. Chang Fox Chase Cancer Center, PA Mario A. Claudino Sao Francisco Univ, Brazil Li Di Pfizer Inc, CT J. Silvio Gutkind Nat Inst of Dental & Craniofacial Res, NIH, MD R. Kiplin Guy St Jude Children’s Res Hosp, TN Magda M. Hagras Suez Canal Univ, Egypt Rhiannon N. Hardwick Organovo, Inc., CA Takayo Inoue Proteostasis Therapeutics, MA Elizabeth A. Jonas Yale Univ, CT Ji-Yong Kang Tufts Univ School of Medicine, MA Hengming Ke Univ of North Carolina Kameswari S. Konduri VGSK Technologies Inc, MA Heather K. Knych Univ of California, Davis

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Raj Kumar Inst of Advanced Sciences, MA Sarah M. Lerchenfeldt Oakland Univ William Beaumont Sch of Med, MI Yvonne S. Lin Univ of Washington Jun-Yan Liu Tenth People’s Hosp of Tongji Univ, China Olufunke E. Ola-Davies Univ of Ibadan, Nigeria Nada M. Porter Univ of Kentucky Bhagwat Prasad Univ of Washington Edilberto A. Raynes Tennessee State Univ Allan E. Rettie Univ of Washington Tannishtha Reya Univ of California, San Diego Aarti Sawant-Basak Pfizer Inc, MA Thomas Simmet Ulm Univ, Germany Bo Zhou Temple Univ, PA William J. Welsh RWJMS, Rutgers Univ, NJ Peter J. West Univ of Utah Dwight Williams Virginia Commonwealth Univ Zuoquan Xie Shanghai Inst of Materia Medica, China Sarah X. Zhang NY Rongjun Zuo Corning Life Sciences, MA

AFFILIATE MEMBERS Bradley W. Main Data Sciences Int’l, MN

POSTDOCTORAL MEMBERS Sagheer Ahmed Univ Brunei Darussalam Ruby A. Fernandez Univ of Arizona Mari D. Heghinian DemeRx, Inc, FL Makan Khoshnejad Univ of Pennsylvania Gayani K. Nanayakkara Temple Univ School of Medicine, PA Pau F. Pascual Garcia Univ of Pennsylvania

GRADUATE STUDENT MEMBERS James L. Akers West Virginia School of Osteopathic Medicine Rawabi A. Alashari MCPHS Univ, MA Heba K. Alshaeri MCPHS Univ, MA Samir H. Barghout Univ of Alberta, Canada Amanda Baun Roseman Univ of Health Sciences, NV Mona Bawazeer Tufts Univ, MA Besma Boubertakh Kunming Inst of Zoology Chinese Acad of Sci, China Thomas J. Cahill NC Carolina Campos Instituto Politecnico Nacional ENCB, Mexico Brandon Y. Chan Univ of Alberta, Canada Leo C. Chukwu Anambra State Univ, Nigeria Justine A. Coburn Univ of Wisconsin- Madison Edgor Cole J. Tolledo Univ of Toronto, Canada

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Stuart A. Collins Univ of Toledo, OH Justine L. Delgado Univ of Iowa Maryvi Gonzalez-Sola Univ of Puerto Rico Med Sci Alqassem Y. Hakam Univ of Toledo, OH Suleman S. Hussain Univ of Texas Health Science Center at San Antonio Uju D. Iliemene Bingham Univ, Nigeria Bina Julian Tufts Medical Center, MA Imran Khan Royal Inst of Medical Sciences, Pakistan Stacey L. Kigar Univ of Wisconsin-Madison Al Hassan Kyakulaga Univ of Louisville, KY Jodi L. MacKeil Queen’s Univ, Canada Yu Mao Roseman Univ of Health Sciences, NV Brandon F. Maziuk Boston Univ, MA Christina Miyabe Northeastern Univ, MA Harrison L. Pantera Univ of Wisconsin-Madison, WI Anh P. Phan Health Science Divisions - Loyola Univ Chicago, IL Gareth S. Purvis WHRI, UK Adam B. Schroer West Virginia Univ Skylar M. Spangler Washington Univ in St Louis, MO Enes Soydemir Univ of East London, UK

Ibrahim Sulaiman Univ Putra Malaysia/Bayero Univ, Malaysia Isha Taneja CSIR-Central Drug Research Inst, India Margarita A. Tararina Boston Univ School of Medicine, MA Jaydeep D. Yadav Temple Univ, PA Mona Zarifpour Wake Forest Inst for Regenerative Medicine, NC Najla D. Zarmouh Florida A&M Univ

UNDERGRADUATE MEMBERS Katherine L. Burrell Univ of Arizona Wayne T. Cottle III Univ of San Diego, CA Kelechi Chitah K. David Univ of Lagos, Nigeria Dane Fickes St. Louis College of Pharmacy, MO Sarah M. Glass Kalamazoo College, MI Faith N. Gonowolo Univ of North Dakota Tyler P. Hinshaw Wake Forest Univ, NC Andrew W. Johansen Univ of Utah Vincent Knecht Juniata College, PA Adam R. Lescallette Juniata College, PA Cecilia Li Univ of Michigan Ziping Liu Rutgers, NJ Jeffrey T. Malotte Univ of Tennessee at Knoxville

Neysha Martinez-Orengo Ponce Health Sci Univ, PR Tyler J. Murphy Oglethorpe Univ, GA Tin Q. Nguyen Univ of Incarnate Word, TX Thomas M. O’Gorman Vanderbilt Univ, TN Victoria H. Osorio Kalamazoo College, MI Jonathan D. Partsch Juniata College, PA Jaileene Perez-Morales Ponce Health Sci Univ, PR Dagoberto Robles Univ of Arizona Jessica L. Scales Juniata College, PA Amelia M. Spaulding Ohio State Univ, College of Pharmacy Sarah J. Sun Vanderbilt Univ, TN Kristian E. Teichert Northeastern Univ, MA Jordan S. Todd Univ of California-San Diego Cesar D. Vargas Vanderbilt Univ, TN Sean D. Watson Michigan State Univ Nolan J. Weinstein Univ of Arizona Christopher Q. White Univ of Central Florida, FL Irene Yang Rutgers Univ, NJ

Are you not receiving ASPET emails? Be sure to add us to your address book or safe sender list! Whitelist our sending email addresses aspet@multibriefs.com and membermail@aspet.ccsend.com so our emails get to your inbox. If you have any questions, email us at membership@aspet.org.

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In Sympathy Dr. William W. Fleming January 30, 1932 – April 29, 2015 (age 83) Submitted by David A. Taylor, PhD and David P. Westfall, PhD

Bill and Dolores Fleming

It is with great sadness that we inform the membership of the death of Dr. William W. Fleming and his wife of 62 years, Dolores. Dr. Fleming and his wife passed away on Wednesday, April 29, 2015 in their home in Tionesta, PA. Bill was born in Washington, DC on January 30, 1932. In early 1946, he moved with his mother to Montana where he graduated from Great Falls High School in 1950. While in high school, he met his wife to be, Dolores Atchison, and they were married in 1952.

Dr. Fleming received numerous fellowships during his undergraduate, doctoral, and postdoctoral training.

With a scholarship, he attended Harvard University, majoring in biology and receiving his AB degree cum laude in 1954. Bill received his PhD in biology in 1957 from Princeton University with an emphasis on

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microvascular physiology. He returned to Boston and the Department of Pharmacology at Harvard Medical School where he began studying autonomic and cardiovascular pharmacology with Drs. Otto Krayer and Ule Trendelenburg with the support of a National Institute of Health (NIH) postdoctoral fellowship. It was during this postdoctoral experience that Bill was exposed to and became immersed in the discipline of pharmacology, which he embraced for the remainder of his illustrious scientific career.

Dr. Fleming left Harvard in 1960 for West Virginia University (WVU) where he was an assistant professor of pharmacology. In 1964, he was promoted to associate professor of pharmacology and in 1966, he became professor and chair of pharmacology, a position that he held until his retirement in 1999. Bill also held the Mylan Endowed Chair of Pharmacology at WVU from 1986 until his retirement. Dr. Fleming was the consummate teacher, and his excellence in teaching was widely recognized by the many awards he received at WVU, including the P.L. MacLachlan Memorial Award for Excellence in Teaching in Basic Medical Science. Dr. Fleming was internationally recognized for his research as well as his ability to mentor PhD students and postdoctoral fellows from all over the world. In 2001, Bill was awarded the Order of the Vandalia by WVU for his outstanding service to the state.

Dr. Fleming’s professional service included three four-year terms on NIH study sections, reviewing grant applications, seven years as a consultant to the Meade Johnson pharmaceutical company and appointments to the editorial boards of the Journal of Pharmacology and Experimental Therapeutics, and Life Sciences and as an ad hoc reviewer for Science, Biochemical Pharmacology, the European Journal of Pharmacology, and the American Journal of Physiology, to name a few. Dr. Fleming was a member of the American Society of Pharmacology

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and Experimental Therapeutics (ASPET), the American Association for the Advancement of Science, the Society for Neuroscience, the American Heart Association (Fellow of the Council on Hypertension Research), and the Association for Medical School Pharmacology Chairs (AMSPC). In addition to his service on multiple ASPET committees, he was president of ASPET and AMSPC, and chair of the ASPET Board of Publications Trustees. Dr. Fleming also served as president of the International Union of Pharmacology, a position that enabled him to travel widely. After his retirement, he was a visiting professor at the University of Nevada at Reno. At the time of his death, Dr. Fleming was not only an emeritus professor of pharmacology and toxicology in the School of Medicine at West Virginia University but also an adjunct professor of pharmacology in the School of Medicine at the University of Pittsburgh.

Dr. Fleming was the recipient of numerous professional and career awards and published over 130 full-length scientific publications. He was the recipient of a Fogarty Senior International Fellowship, ASPET’s Otto Krayer Award in 1986, and the Torald Sollman Award in Pharmacology in 1999. As part of three research sabbaticals, Dr. Fleming served as visiting professor in the laboratory of Professor Geoffrey Burnstock in the Department of Zoology at the University of Melbourne and Adelaide, Australia (1969). In 1978, Dr. Fleming was a visiting professor in the laboratory of Dr. T. B. Bolton in the Department of Pharmacology at St. George’s Hospital at the University of London. In 1987, he was visiting professor at the University of Adelaide in the laboratory of Dr. S. Johnson.

Dr. Fleming’s research focused on understanding the influence of external chronic interventions

on the responsiveness of smooth muscle and other excitable tissues to drugs and physiological manipulations. He was a pioneer in the concept of supersensitivity and subsensitivity of excitable membranes and helped define and characterize these concepts and their underlying mechanisms.

His observations have had major implications for our understanding of tolerance and drug dependence as well as epilepsy and hypertension. His research on the cellular mechanisms responsible for the change in responsiveness of the effector cells following chronic alteration in neuronal input provided the first description of a single molecular alteration responsible for the augmentation of effector cell sensitivity to drugs In 2003, he and his wife, Dolores, moved to Tionesta, PA, where one of their daughters resides and he resumed his life-long interest in building ship models to the scale of 1:350. He had built a fleet of over 50 ships mostly from vessels active during World War II. He was also known for his extensive model train collection, which occupied an entire room of their home.

In addition to the lifelong friends and colleagues they had in the scientific community, Dr. Fleming and his wife are survived by their two daughters, Jennifer Hitchcock and her husband, Mark, of Tionesta, PA; Lisa Foster and her husband, Preston, of San Antonio, TX; a son, Dr. David Fleming and his wife, Kathleen, of Edwardsburg, MI; five grandchildren Matthew Hitchcock and his girlfriend, Angela Vitale, of Conway, SC; Christopher Hitchcock and his wife, Amy, of Pittsburgh, PA; Kara Foster and Paige Foster, both of San Antonio, TX; Lincoln Fleming of Michigan; and a great-grandson, Owen Hitchcock.

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Members-in-the-News Achievements, Awards, Promotions, and Scientific Breakthroughs

Dr. Siddhartha Ray Manchester University

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Dr. Siddhartha Ray, professor of pharmaceutical sciences has been named the editor of the prestigious monograph Side Effects of Drugs: Annual or SEDA. This prestigious international book, published since 1977 by Elsevier, is a case-studybased annual monograph well known to practitioners as SEDA for four decades. SEDA reviews case studies on the side effects of drugs, drug-induced adverse events, and drug-induced toxic reactions. This annual publication complements Meyler’s Side Effects of Drugs— The International Encyclopedia of Adverse Drug Reactions and Interactions, published every 10 years.

Professor Ray received the Senior Toxicologist Award from the Association of Scientists of Indian Origin, a special interest group of the Society of Toxicology. This honor

was awarded during the 2015 Annual Society of Toxicology meeting held in San Diego, CA, March 22–26.

Dr. Ray perseveres to promote lifelong learning strategies among his students and clearly models his beliefs as a mentor. He has been a member of ASPET since 1999 and primarily affiliated with the Division for Toxicology.

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Division News 2015 Division Award Winners Division for Behavioral Pharmacology Best Abstract Competition Winners (Poster Sessions) In the undergraduate category, top prizes went to Sneha Gupta (1st) from Washington and Jefferson College and Caitlin Caperton (2nd) from the University of Arkansas, Little Rock. (Photo unavailable)

Top prizes for graduate students went to Brenda Gannon (1st) from the University of Arkansas for Medical Sciences and Alison Wakeford (2nd) from the University of Texas Health Science Center at San Antonio.

Top prizes for postdoctoral scientists went to Katherine Serafine (1st) from University of Texas Health Science Center at San Antonio and Harshini Neelakantan (2nd) from the University of Texas Medical Branch.

Division for Cardiovascular Pharmacology Best Abstract Competition Winners (Poster Sessions)

In the graduate student category, the top prizes were awarded to Arsalan Syed (1st) from the University of Vermont, Benjamin Leiblong (2nd) from the University of Arkansas for Medical Sciences, Kristin Luther (3rd) from the Loyola University of Chicago, and Hari Priya Vemana (4th) from the Western University of Health Sciences.

In the postdoctoral scientist category, the top prizes went to Stephen Kraynik (1st) from the University of Cincinnati, Zichao Zhu (2nd) and Xueping Zhou (3rd) from West Virginia University, and Wuqiang Zhu (4rd) from the University of Minnesota. (Pictured here: Zichao Zhu and Xueping Zhou)

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Cardiovascular Trainee Showcase Winners (Oral Sessions)

In the CVP Trainee Showcase graduate student category, the top prizes for trainee talks went to Cam McCarthy (1st) from Georgia Regents University, Yiwei Liu (2nd) from Auburn University, and Haobo Li (3rd) from the University of Hong Kong. (Pictured here: Cam McCarthy and Yiwei Liu)

Benjamin Tourdot (1st) from Thomas Jefferson University, Laurel Grisanti (2nd) from Temple University, Thiago Bruder-Nascimento (3rd) from the Georgia Regents University, and Deepesh Pandey (4th) from Johns Hopkins University won the top prizes for postdoctoral trainee talks.

Benedict R. Lucchesi Distinguished Lectureship in Cardiac Pharmacology

Dr. Scott Waldman presented a beautiful custom designed crystal bowl to Dr. Terzic in appreciation of his outstanding contributions to the Society.

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Andre Terzic, MD, PhD was awarded the Benedict R. Lucchesi Award in Cardiac Pharmacology on behalf of the Cardiovascular Pharmacology Division this year at Experimental Biology 2015. Dr. Terzic was recognized for the prestigious award in 2013 and was invited to deliver his state of the-art-lecture at Experimental Biology 2015 this past spring in Boston, MA. Dr. Terzic delivered his talk to a large attentive audience and his presentation was titled “Regenerative Therapy for the Failing Heart”. The Benedict R. Lucchesi Award in Cardiac Pharmacology was established to honor Dr. Lucchesi’s illustrious lifelong scientific contributions and for his exceptional dedication as a mentor in the field of cardiovascular pharmacology.

Dr. Terzic is a professor of medicine and pharmacology at the Mayo Clinic in Rochester and is a pioneer in the field of regenerative medicine serving as the director of the Mayo Clinic’s Center for Regenerative Medicine. On behalf of the Cardiovascular Division Award Committee, Dr. Terzic received an honorarium, a beautifully custom designed crystal bowl, and travel expenses in recognition of his meritorious career in cardiac research and for outstanding contributions and service to ASPET and the Cardiovascular Pharmacology Division.

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Division for Drug Discovery and Development Best Abstract Competition Winners (Poster Sessions)

Read about the 2015 Early Career Achievement Award winner Dr. Nmandje Bumpus in our March issue: bit.ly/18SAW69

Top prizes for young scientists went to Rohun Palekar (1st) and Andrew Jallouk (2nd) from Washington University-St. Louis, and Zohar Weinstein (3rd) from Boston University. Natalie Arabian from the University of Southern California won the top prize in the undergraduate research category.

Division for Drug Metabolism Best Abstract Competition Winners (Poster Sessions)

Top prizes for graduate students went to Julie Lade (1st) from the Johns Hopkins School of Medicine, Zufei Zhang (2nd) from the University of Washington, Seattle, and Xian Pan (3rd) from the University of Illinois, Chicago.

Top prizes for postdoctoral scientists were awarded to Yun Chen Tien (1st) from the University of Connecticut School of Pharmacy, Ji Won Park (2nd) from the Louisiana State University HSC, and Ian Cook (3rd) from the Albert Einstein College of Medicine.

James R. Gillette Best Paper Award The Division for Drug Metabolism annually awards the James R. Gillette Best Paper Awards for the best papers published in the ASPET journal Drug Metabolism and Disposition. Two awards were presented in the areas of (a) drug metabolism and (b) pharmacokinetics during the ASPET Annual Meeting at EB 2015.

Kunzhi Jia accepted the award in Drug Metabolism for his paper titled “Generation and Characterization

of a Novel CYP2A13-Transgenic Mouse Model.” Due to travel restrictions, Dr. Jia’s paper was presented by Xinxin Ding.

Toru Takenaka accepted the award in Pharmacokinetics and presented the paper titled “Human Small Intestinal Epithelial Cells Differentiated from Adult Intestinal Stem Cells as a Novel System for Predicting Oral Drug Absorption in Humans.”

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Division for Translational and Clinical Pharmacology

Young Investigator Platform Session Winners (Oral Sessions)

Best Abstract Competition Winners (Poster Sessions)

Top prizes for graduate students went to Shravan Kumar Sriraman (1st) from Northeastern University, Amanda Stolarz (2nd) from University of Arkansas for Medical Sciences, and Mohamed Ghonim (3rd) from the Louisiana State University School of Medicine. Ericka Anderson from UCSD Medical School won the top prize in the postdoctoral category.

In the Young Investigator Platform Session, first, second, and third places for graduate student talks went to Brian Gall (1st) from West Virginia University, Jennifer Yeung (2nd) from Thomas Jefferson University, and Clark Sims (3rd) from the University of Arkansas for Medical Sciences. Kai Zou (1st) from East Carolina University and Ashley Guillory (2nd) from the University of Texas Medical Branch won the top prizes for postdoctoral trainee talks.

Division for Molecular Pharmacology Best Abstract Competition Winners (Poster Sessions)

Top prizes for graduate students went to Kathryn Livingston (1st) from University of Michigan, Nicole Brown (Finalist) and Kyle Gerber (Finalist) from Emory University, Jacob Mahoney (Finalist) from University of Michigan, and Chen-Shan Woodcock (Finalist) of the University of Pittsburgh School of Medicine.

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Amy Moritz from NINDS/NIH won the top prize in the postdoctoral category.

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Division for Neuropharmacology Best Abstract Competition Winners (Poster Sessions)

The top prizes were awarded to Alex Nackenoff (1st) from Vanderbilt University, Nathan Mitchell (2nd) from the University of Texas HSC-San Antonio, and Branden Stansley (3rd) from the University of Toledo College of Medicine.

Division for Toxicology Best Abstract Competition Winners (Poster Sessions)

The top prizes for graduate students were awarded to Blessy George (1st) from Rutgers University, Zhengxi Wei (2nd) from the University of Rhode Island, Alessandro Venosa from Rutgers University (3rd), and Rebecca Crawford (3rd) from Louisiana State University Health Sciences Center.

Postdoctoral Scientist Award Winners (Oral Sessions)

Four other graduate students qualified as finalists: Le Zhan and Mary Francis from Rutgers University, Christopher Racine from Marshall University, and Aram Cholanians from the University of Arizona.

The top prizes for postdoctoral scientist talks went to Karen Tonsfeldt (1st) from the Oregon Health and Science University, Rheaclare Fraser (2nd) from the University of Texas Health Science Center at San Antonio, and Erin Bobeck (3rd) from the Mount Sinai School of Medicine.

Read about the 2015 Junior and Career Investigator Award winners Jason Richardson, PhD, and Curt Omiecinski, PhD in our March issue: bit.ly/18SAW69

Read about the 2015 Early Career Investigator Award winner Daniel J. Lodge, PhD in our March issue: bit.ly/18SAW69

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2015 Division Mixers The ASPET division-sponsored mixers at EB 2015 presented a great opportunity for members to mingle with friends and colleagues from their respective divisions.

Members enjoyed great food, drinks, and plenty of opportunities to network and catch up with fellow division peers. Many divisions also held their award ceremonies at the mixers.

View our photo collection from the annual meeting on Flickr: www.flickr.com/photos/aspet_photo_gallery/

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Division for Pharmacology Education Inducts Two New Fellows into the Academy of Pharmacology Educators The Academy of Pharmacology Educators was established in 2010 in order to recognize individuals who have made exemplary contributions to pharmacology education in one or more of the following areas: student-teacher interaction, innovative contributions, scholarly endeavors, professional development and service. Two new members were inducted into the Academy during the Annual Meeting of the Division for Pharmacology Education at EB 2015. More information about the Academy, including application instructions and a roster of inductees, can be found here: www.aspet. org/Education/Academy.

University of Ireland Galway in Ireland as a lecturer.

In 2006, he joined St. Mathew’s University, School of Medicine in Grand Cayman, where he served as professor, dean of Basic Sciences and director of the Center for Excellence in Medical Education (CEME). In 2012, he joined Oakland University William Beaumont School of Medicine (OUWB), where he served as the co-director of the CEME and associate professor in the Division of Biomedical Sciences. Currently he serves as an assistant dean for Academic Affairs and professor of Pharmacology in the Department of Physiological Sciences at Eastern Virginia Medical School, where he leads a major curriculum reform project. He has received multiple awards for teaching excellence including the institutional Golden Apple awards and the Pharmacology Education Award given by ASPET’s Division for Pharmacology Education. He also serves as a senior advisor for the World Federation for Medical Education and a deputy editor of the reputed Teaching and Learning in Medicine Journal. He has been actively engaged with ASPET since 2004 as a student member, and since 2008 as a regular member. He is a primary member of the Division for Pharmacology Education, and served as its secretary/treasurer from 2011–2013.

Dr. Senthil K Rajasekaran with the chair of the Division of Pharmacology Education Dr. Carol Beck.

The first 2015 Academy inductee is Senthil K. Rajasekaran, MD. Dr. Rajasekaran received his MD from Moscow State University of Medicine and Dentistry in 1997 after which he completed his postgraduate medical training in basic and clinical pharmacology at Sri Ramachandra University in Chennai, India in 2004.

He has been involved in medical education and the teaching of pharmacology for more than 14 years.

He has taught pharmacology for medical, nursing, pharmacy, dental, physician assistant, and other allied health courses. In 2004 he joined the National

Dr. Robert P. Soltis with the chair of the Division of Pharmacology Education Dr. Carol Beck.

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The second 2015 Academy inductee is Robert P. Soltis, PhD. Dr. Soltis is the Ellis and Nelle Levitt Distinguished Professor of Pharmacology at Drake University, College of Pharmacy and Health Sciences. He received his bachelor’s in pharmacy from Butler University and a PhD in pharmacology from Indiana University. Prior to joining the faculty at Drake University, Dr. Soltis was a Pharmacology Research Associate (PRAT Fellow) at the National Institutes of Health. Dr. Soltis’ lab-based research program focuses on central mechanisms regulating the cardiovascular and neuroendocrine response to stress. In recent years, he has pursued the scholarship of teaching and learning focusing on process oriented guided inquiry learning. His area of teaching includes

neuropharmacology, autonomic pharmacology, and mechanisms of drug interactions. He is a co-author of the textbook Introduction to the Pharmaceutical Sciences: An Integrated Approach. He has received the College Teacher of the Year Award three times and the College Professional Leadership Award and Distinguished Professor Award. He has also worked to advance pharmacology education through his service to the US Pharmacopeial Convention, American Association of Colleges of Pharmacy, the Accreditation Council for Pharmacy Education, and others. He has been an ASPET member since 1993, and a primary member of the Division for Pharmacology Education for the past 10 years.

Division for Pharmacology Educations Extends the Terms of Current Leadership

Carol Beck, Chair

Robert J. Theobald, Secretary/Treasurer

Kelly Karpa, Chair-Elect

Jayne Reuben, Secretary/ Treasurer-Elect

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In light of the merger between the Division for Pharmacology Education (DPE) and the Graduate Recruitment and Education Committee (GREC), which became effective on July 1, 2014 and involved expanding the Executive Committee to include the leadership of both groups, Council agreed to extend the terms of the current chair and secretary/treasurer by one year. The decision not to hold an election was made in order to ease the merger and to maintain the continuity of ongoing programs during the transition. Carol Beck and Robert Theobald will serve as chair and secretary/treasurer, respectively, until June 30, 2016. Members of the merged Executive Committee were asked to self-nominate for the positions of chair-elect and secretary-treasurer-elect. From these self-nominations, Council selected Jayne Reuben (chair-elect) and Kelly Karpa (secretary/treasurer-elect) to serve one year terms as officer-elect (July 1, 2015–June 30, 2016), followed by two-year terms of office (July 1, 2016– June 30, 2018). The division has proposed a regular election cycle that will take effect in 2016 to fill the roles of chair-elect and secretary/treasurer-elect, with one-year officer-elect terms beginning on July 1, 2017 and two-year terms in office beginning in 2018.

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Division for Drug Discovery and Development Selects New Officers The executive committee of the DDD has decided to move elected and appointed terms for officers to a 1 year cycle, coordinating with the cycle of officers in ASPET. To facilitate an annual election, the DDD has selected and Council has approved Robert J. Leadley, Jr., PhD and Craig Beeson, PhD for the offices of Chair and Secretary/Treasurer, respectively. Dr. Leadley and Dr. Beeson will begin their terms on July 1, 2015 for the 2015/2016 year. An election for 2016/2017 officers will be held in December of this year.

Robert Leadley, Chair

Craig Beeson, Secretary/Treasurer

Announcing the New ASPET Division for Cancer Pharmacology ASPET is pleased to announce the formation of the Division for Cancer Pharmacology. Although cancer pharmacology has been represented in other ASPET divisions, interest in cancer pharmacology topics has continued to grow among our members and it is clear that a division devoted specifically to this discipline is both timely and necessary. The Division for Cancer Pharmacology is the ‘go-to’ place for cancer pharmacologists to gather and share experiences and to form productive networks and collaborations. Members interested in cancer pharmacology are encouraged to join this new division as either a primary or secondary member.

Mission Statement The mission of the Division for Cancer Pharmacology is to serve members with interests in all aspects of basic and translational cancer pharmacology research. Specific areas include, (but are not limited to) discovery and pre-clinical

development of new anticancer agents, preclinical toxicology and adverse reactions to anticancer drugs, technical developments in novel cancer-related target and therapeutic identification, mechanisms of anticancer drug resistance, mechanisms of anticancer drug action, mechanistic studies of novel therapeutic regimens, pharmacogenetics of anticancer therapeutics, and biomarker studies in anticancer drug response.

For more information about the Division for Cancer Pharmacology, please visit online at www.aspet.org/ Cancer_Pharmacology_home.

Executive Committee To help get this division off the ground, Council appointed Dr. Susan P.C. Cole, from Queen’s University Cancer Research Institute in Kingston, ON as Chair and Dr. R. Kiplin Guy, from St. Jude’s Research Hospital in Memphis, TN as Secretary/Treasurer.

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Division Activities

Susan Cole Queen’s University Cancer Research Institute

During the 2016 symposium proposal submission process this year, the cancer pharmacology division received an impressive number of high quality symposium proposals.

The division looks forward to an excellent year for the inaugural cancer pharmacology programming at the annual meeting at EB 2016 in San Diego. In addition to the scientific programming at the annual meeting, future division activities will include awards for cancer pharmacologists who have made exceptional contributions to the field, best abstract and presentation competitions and awards, and of course, social activities such as a mixer at the annual meeting.

These activities will be enhanced whenever possible by working collaboratively with other ASPET divisions as relevant.

success. Consider joining the division, as either a primary or secondary member. To do this, please log in to your ASPET account at www.aspet. org, click on “Member Homepage,” and then click on “Update My Information.” You may choose “Cancer Pharmacology” as either your primary or one of your secondary divisions.

If you have any issues logging in, please contact ASPET’s membership department at membership@aspet.org or by phone at 301.634.7060.

Please spread the word - don’t forget to tell your colleagues, students, and friends about the new ASPET Division for Cancer Pharmacology and encourage them to join!

If you have any ideas, suggestions, or would like to get involved in the Division for Cancer Pharmacology, please contact Susan Cole at spc.cole@queensu.ca and/or Kip Guy at kip.guy@stjude.org.

Join the Division for Cancer Pharmacology Your help is needed to make the cancer pharmacology division a

Have You Joined a Division?

Kip Guy St. Jude’s Research Hospital

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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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Meetings & Congresses June 2015 24th Ann. Mtg. of the Int’l Behavioral Neuroscience Soc. www.ibnsconnect.org/?page=2015_Meeting June 2–7, Victoria, British Columbia, Canada Amer. Diabetes Assn. 75th Scientific Sessions professional.diabetes.org/Congress_Display. aspx?TYP=9&CID=95010 June 5–9, Boston, MA MicroRNAs & Noncoding RNAs in Cancer www.keystonesymposia.org/index. cfm?e=web.Meeting.Program&meetingid=1316 June 7–12, Keystone, CO World Cong. on Medical Physics & Biomedical Engineering www.wc2015.org June 7–12, Toronto, Canada

Animal-Microbe Symbioses: Identifying the Common Language of Host-Microbe Associations www.grc.org/programs.aspx?id=16842 June 21–26, Waterville Valley, NH 5th Int’l Regional Stress & Behavior Neuroscience & Biopsychiatry Conf. www.stressandbehavior.com June 22–24, Miami, FL Int’l Soc. for Stem Cell Res. www.isscr.org/home/annual-meeting/ isscr2015 June 24–27, Stockholm, Sweden Summer School on Stress www.stresseducation.org June 29–July 2, Grenoble, France

July 2015

2015 AAPS Nat. Biotechnol. Conf. www.aaps.org/nationalbiotech June 8–10, San Francisco, CA

Soc. for Develop. Biology 74rd Ann. Mtg. www.sdbonline.org/2015mtg July 9–13, Snowbird, UT

Apoptotic Cell Recognition & Clearance: Responses to Apoptotic Cells Leading to Inflammatory Resolution & Pathogenesis www.grc.org/programs.aspx?id=14625 June 13–14, Biddeford, ME

2015 Nat’l Directors of Graduate Studies in Pharmacology & Physiology Mtg. www.the-aps.org/ndogs2015 July 10–12, Cincinnati, OH

DIA 2015 www.diahome.org/en-US/Flagship-Meetings/ DIA-Annual-Meeting/About-the-Conference. aspx June 14–18, Washington, DC Apoptotic Cell Recognition & Clearance: Physiological Significance & Pathological Consequences www.grc.org/programs.aspx?id=13127 June 14–19, Biddeford, ME 2015 Int’l Narcotics Res. Conf. www.inrcworld.org/2015/2015mtg.htm June 15–19, Phoenix, AZ Autophagy www.keystonesymposia.org/ index.cfm?e=web.Meeting.

Program&meetingid=1322 June 19–24, Breckenridge, CO

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The Allied Genetics 2016 Conf. www.genetics2016.org July 13–17, Orlando, FL Melatonin Biology: Actions & Therapeutics www.faseb.org/SRC-Mela/Home.aspx July 19–24, Lisbon, Portugal Protein Kinases & Protein Phosphorylation www.faseb.org/SRC-PKPP/Home.aspx July 19–24, Itasca, IL Protein Lipidation, Signaling & Membrane Domains www.faseb.org/SRC-ProLip/Home.aspx July 19–24, Saxtons River, VT 15th Int’l Fragile X Conf. www.fragilex.org/community/internationalfragile-x-conference July 20–24, San Antonio, TX 29th Symp. of the Protein Soc. www.barcelocongresos.com.es/protein2015/ welcome.html July 22–25, Barcelona, Spain Int’l Acad. of Cardiology Ann. Sci. Sessions 2014/20th World Cong. of Heart Disease www.cardiologyonline.com/wchd2014/index. html July 25–27, Vancouver, BC

Tuberculosis Drug Discovery & Development: New Strategies to Fight an Old Enemy www.grc.org/programs.aspx?id=15775 July 11–12, Girona, Spain

6th Int’l Neuroscience & Biological Psychiatry ISBS Conf. www.stressandbehavior.com July 26-27, Kobe, Japan

Tufts University: Molecular Therapeutics of Cancer Research Conf. www.aspet.org/uploadedFiles/Meetings/ Other_Meetings/tufts%20poster%202015.pdf July 12–16, Boston, MA

42st Ann. Mtg. & Expo. of the Controlled Release Soc. www.controlledreleasesociety.org/meetings/ annual/overview/Pages/default.aspx July 26–29, Edinburgh, Scotland

The TGF-ß Superfamily: Signaling in Development & Disease www.faseb.org/SRC-TGFB/Home.aspx July 12–17, Snowmass, CO

Japan Neurosci. Soc. 37th Ann. Mtg. www.neuroscience2015.jnss.org/e/outline. html July 28–31, Kobe, Japan

Drug Metabolism: Solving Knowledge Gaps in Drug Metabolism & Pharmacokinetic Prediction, Improving Translational Medicine www.grc.org/programs.aspx?id=11186 July 12–17, Holderness, NH

August 2015 Epigenetics: Mechanisms of Mitotic & Meiotic Epigenetic Inheritance www.grc.org/programs.aspx?id=17018 Aug. 1–2, Waltham, MA

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Gastrointestinal Tract XVI: GI Homeostasis: The Microbiome & the Barrier, Development & Disease www.faseb.org/SRC-Gastro/Home.aspx Aug. 2–7, Steamboat Springs, CO Amer. Psychological Assn. Ann. Conv. www.apa.org/convention Aug. 6–9, Toronto, ON Catecholamines: Frontiers in Catecholamine Function from Synapses to Disease www.grc.org/programs.aspx?id=14061 Aug. 8–9, Newry, ME Cellular & Molecular Mechanisms of Toxicity: Advanced In Vitro Models in Mechanistic Toxicology www.grc.org/programs.aspx?id=15534 Aug. 8–9, Andover, NH 12th World Cong. on Inflammation www.inflammation2015.org Aug. 8–12, Boston, MA Molecular & Systems Integration of Genomic & Nongenomic Steroid Hormone Action www.faseb.org/SRC-Steroid/Home.aspx Aug. 9–14, Big Sky, MT NAD+ Metabolism & Signaling www.faseb.org/SRC-NAD/Home.aspx Aug. 9–14, Timmendorfer Strand, Germany Hormone-Dependent Cancers: Mechanisms to Tailored Therapeutics www.grc.org/programs.aspx?id=13373 Aug. 16–21, Newry, ME

67th Clin. Endocrinology Update www.endocrine.org/ceu Sept. 10–12, Miami, FL

20th North Amer. ISSX Mtg. www.issx.site-ym.com/page/20NAISSXInvite Oct. 18–22, Orlando, FL

North Amer. Artery 5th Ann. Mtg. www.naartery.org Sept. 11–12, Chicago, IL

Int’l Soc. for Applied Cardiovascular Biology & NAVBO www.navbo.org/events/vb2015 Oct. 18–22, Hyannis, MA

Eurotox: 51st Cong. of the Europ. Socs. of Toxicol. www.eurotox2015.com Sept. 13–16, Porto, Portugal 21st Scientific Symp. of the Austrian Pharmacological Soc. www.bps.ac.uk/meetings/14844de2424 Sept. 16-18, Graz, Austria The Mobile Genome: Genetic & Physiological Impacts of Transposable Elements bit.ly/1DIHbDq Sept. 16–19, Heidelberg, Germany Int’l Soc. for Eye Res. XXII Biennial Mtg. www.iserbiennialmeeting.org Sept. 26–30, Tokyo, Japan Amer. College of Clin. Pharmacology Ann. Mtg. accp1.org/2015_meetings_welcome.shtml Sept. 27–29, San Francisco, CA 15th Ann. Mtg. of Safety Pharmacology Soc. www.safetypharmacology.org/ annualmeetings.asp Sept. 28–Oct. 1, Prague, Czech Republic

October 2015

Histone Deacetylases & Sirtuins in Biology, Disease & Aging www.faseb.org/SRC-HDAC/Home.aspx Aug. 16–21, Timmendorfer Strand, Germany

2015 Amer. Soc. of Human Genetics www.ashg.org/2015meeting/index.shtml Oct. 6–10, Baltimore, MD

Lysophospholipids & Related Mediators— From Bench to Clinic www.faseb.org/SRC-LysoLipid/Home.aspx Aug. 23–28, Banff, Canada

2015 IPA Int’l Cong. www.ipa-online.org/wordpress/event/2015international-congress-berlin Oct. 13–16, Berlin, Germany

28th ECNP Cong. www.ecnp-congress.eu Aug. 29–Sept. 1, 2015

25th Neuropharmacology Conf. 2015 www.neuropharmacology-conference. elsevier.com Oct. 15–16, Chicago, IL

September 2015 Amer. Physiological Soc. 14th Ann. Conf. on Endothelin www.the-aps.org/et-14 Sept. 2-5, Savannah, GA 2015 DIA/FDA Oligonucleotide-based Therapeutic Conf. bit.ly/16NZaOM Sept. 9-11, Washington DC

Advances in Breast Cancer Res. www.aacr.org/Meetings/Pages/MeetingDetail. aspx?EventItemID=49#.VWTTrWdFCUk Oct. 17–20, Bellevue, WA

2015 Soc. of Forensic Toxicologists Ann. Mtg. www.soft-tox.org/meeting Oct. 19–23, Atlanta, GA 4th AACR Int’l Conf. on Frontiers in Basic Cancer Res. www.aacr.org/Meetings/Pages/MeetingDetail. aspx?EventItemID=59#.VWTTdmdFCUk Oct. 23–26, Philadelphia, PA 2015 SACNAS Nat. Conf. www.sacnas.org/events/national-conf Oct. 29–31, Washington, DC

November 2015 Pharma Middle East 2015 middleeast.pharmaceuticalconferences.com Nov. 2–4, Dubai, UAE Amer. Soc. of Nephrology: Kidney Week 2015 www.asn-online.org/education/kidneyweek Nov. 3–8, San Diego, CA AACR-NCI-EORTC Int’l Conf. on Molecular Targets & Cancer Therapeutics www.aacr.org/Meetings/Pages/MeetingDetail. aspx?EventItemID=59#.VWTTdmdFCUk Nov. 5–9, Boston, MA Translational Cancer Res. for Basic Scientists Workshop www.aacr.org/Meetings/Pages/MeetingDetail. aspx?EventItemID=67#.VWXQL2dFCUk

Nov. 8–13, Boston, MA 63rd Amer. Soc. of Cytopathology Ann. Scientific Mtg. www.cytopathologymeeting.org/2015 Nov. 13–16, Chicago, IL 8th AACR Conf. on the Science of Cancer Health Disparities in Racial/Ethnic Minorities & the Medically Undeserved www.aacr.org/Meetings/Pages/MeetingDetail. aspx?EventItemID=68#.VWXSeGdFCUk Nov. 13–16, Atlanta, GA

Soc. for Neuroscience: Neuroscience 2015 www.sfn.org/annual-meeting/ neuroscience-2015 Oct. 17–21, Chicago, IL

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Cardiovascular, Renal & Metabolic Diseases: Physiology & Gender www.the-aps.org/mm/Conferences/APSConferences/2015-Conferences/Physiologyand-Gender Nov. 17–20, Hyannis, MA Developmental Biology & Cancer www.aacr.org/Meetings/Pages/MeetingDetail. aspx?EventItemID=67#.VWXQL2dFCUk Nov. 30–Dec. 3, Boston, MA

The Pharmacologist • June 2015

December 2015 EORTC-NCI-EMA-AACR Int’l Conf. on Innovation & Biomarkers in Cancer Drug Development www.aacr.org/Meetings/Pages/MeetingDetail. aspx?EventItemID=71#.VWXS6mdFCUk Dec. 3–4, Brussels, Belgium 54th Ann. Mtg. of the Amer. Coll. of Neuropsychopharmacology www.acnp.org/annualmeeting/default.aspx Dec. 6–10, Hollywood, FL

San Antonio Breast Cancer Symp. www.sabcs.org Dec. 8–12, San Antonio, TX 2015 Ann. Mtg. of the Amer. Soc. of Cell Biology

www.ascb.org/2015meeting Dec. 12–16, San Diego, CA

2015 British Pharmacological Soc. Mtg. www.bps.ac.uk/meetings/ Pharmacology2015 Dec. 15–17, London, UK