The Pharmacologist June 2022 by ASPET

the

A Publication by The American Society for Pharmacology and Experimental Therapeutics

Pharmacologist Vol. 64 • Number 2 • June 2022

Lithium: INSIDE

Battering Mania EB 2022 Wrap Up Call for 2023 Award Nominations ASPET 2023 Meeting

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

Contents 1 3 8 10 14 16 28 31 34 36 39 44 46

Message from the President 2022 Annual Meeting Highlights EB 2022 Wrap up Call for 2023 Award Nominations Meet the 2022-2023 ASPET Council Feature Story: Lithium: Battering mania Education News Science Policy News ASPET 2023 Meeting News Journals News Membership News Chapter News Division News

THE PHARMACOLOGIST PRODUCTION TEAM Catherine L. Fry, PhD Lynne Harris, MA, APR Dave Jackson, MBA, CAE Maria Pasho COUNCIL President Margaret E. Gnegy, PhD President Elect Michael F. Jarvis, PhD, FBPhS Past President Charles P. France, PhD Secretary/Treasurer Carol L. Beck, PharmD, PhD Secretary/Treasurer Elect Kathryn A. Cunningham, PhD Past Secretary/Treasurer Mary-Ann Bjornsti, PhD Councilors Namandjé N. Bumpus, PhD Randy A. Hall, PhD John R. Traynor, PhD Chair, Publications Committee Kenneth Tew, PhD, DSc, FASPET Chair, Program Committee Michael W. Wood, PhD FASEB Board Representative Catherine M. Davis, PhD Executive Officer Dave Jackson, MBA, CAE The Pharmacologist (ISSN 0031-7004) is published quarterly in March, June, September, and December by the American Society for Pharmacology and Experimental Therapeutics, 1801 Rockville Pike, Suite 210, Rockville, MD 20852-1633. Annual subscription rates: $25.00 for ASPET members; $50.00 for U.S. nonmembers and institutions; $75.00 for nonmembers and institutions outside the U.S. Single copy: $25.00. Copyright © 2022 by the American Society for Pharmacology and Experimental Therapeutics Inc. All rights reserved. Periodicals postage paid at Rockville, 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, 1801 Rockville Pike, Suite 210, Rockville, MD 20852-1633.

Message from

The President Dear ASPET members, This is my last President’s Message. While I will miss being able to serve as your President, I am encouraged by the progressive programs instituted in ASPET during this year. The Inclusion, Diversity, Equity, and Accessibility (IDEA) Task Force is diligently working to institute greater culture awareness within the Society. In recognition of the areas to be considered, the task force has adopted a name change to IDEA Task Force, Inclusion, Diversity, Equity, and Accessibility. The importance of IDEA to pharmacology was delineated beautifully by Dr. L’Aurelle Johnson in her speech at the ASPET Presidential Symposium during EB 2022. Hand in hand with instituting more IDEA in ASPET is the need to increase diversity in membership and, of course, to increase membership. To that end, we have established a Membership Task Force that is dedicated to assessing membership trends, exploring ways to increase the diversity of members with respect to their different work environments and stepping up our efforts to provide membership with benefits from ASPET. I am very excited for ASPET to reap the fruits of both task forces. Another important task force is the Bylaws Task Force, which is pulling the by-laws out of their 1925 origins and propelling them into 2022 – and it’s not an easy task. Their endeavors, however, will create a more solid governance structure for ASPET. I so very much enjoyed the EB 2022 meeting. It was such fun to see so many of you face to face, even mask to mask. I especially enjoyed the students. Their enthusiasm was infectious. The pharmacology attendance was nearly 1,200 participants. The sessions were all so interesting that it was hard to choose from among those offered at the same time. Always a problem, isn’t it? Rumor has it that the ASPET Student/Postdoc Mixer was such a good party that it could serve as a recruiting event for students in other societies. I want to commend all who attended EB 2022 and for helping to make the last EB meeting such a great event, certainly for ASPET. Let us carry that enthusiasm into 2023. We have great plans for ASPET 2023. St. Louis is a great venue for many reasons, involving activities and cost among other features. St. Louis Union Station, the site of our meeting, is elegant and charming. We are planning to feature top-notch science, innovative programming, and several member social activities. Be sure to mark the date on your calendars right now: Thursday May 18 Sunday, May 21, 2023. It has been my pleasure to serve as the President of ASPET this year. Having been an ASPET member since 1981, I have always known it was a special Society; it became my societal home. However, I became much more aware of how the Society serves its members since becoming President. The Society owes a debt of thanks to its members (for what is a Society without its members?). ASPET is blessed with many dedicated, hard-working, and caring members populating its numerous committees and giving hours of their time and effort serving ASPET and the cause of pharmacology. There are those who have been serving the Society for years and young students just beginning their journey. It is so impressive. Equally impressive is the ASPET staff. Every staff member is skilled, hard-working, and dedicated to the Society. A President always wants to think that they have left their purview a better place than when they came. That tends toward hubris because ASPET was doing well when I became President and changes are really group efforts. However, there have been programs developed during my term that I think have put ASPET onto a

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2 good path and will help it meet the future with strength. I look forward to working as Past President with Mike Jarvis, our incoming president. Mike has dedicated himself to ASPET for years and will be an excellent and knowledgeable President. Having worked for years in industry, he will inject diversity into Society planning. As you know, I am committed to expanding the fields of pharmacologists who are ASPET members. We very much want ASPET to be a home for all pharmacologists. So, work on your research this year, write those abstracts and submit them for ASPET 2023. Put on your party hats and -- Meet me in St. Louis! (If you don’t know the song, look it up). Sincerely,

Margaret E. Gnegy, PhD ASPET President

St. Louis Union Station Hotel May 18–21

Meet us in St. Louis! The Pharmacologist • June 2022

2022 Annual Meeting Highlights The Intersectionality of Health Disparities— Pharmacology, Prescribing Bias, and Social Determinants of Health Submitted by Dr. Margaret E. Gnegy, PhD As pharmacologists and educators who are training the next generation of scientists and clinicians, we must acknowledge the bias and social determinants of health that impact the health and wellbeing of our country’s citizens. Jayne S. Reuben, PhD, Associate Professor and Director of Instructional Effectiveness, Texas A&M University College of Dentistry kicked off the Presidential Symposium at the 2022 ASPET Annual Meeting at Experimental Biology. “We are concerned about the constant use of federal funds to support this most notorious expression of segregation. Of all the forms of inequality, injustice in health is the most shocking and the most inhuman because it often results in physical death.” In 1966, the Reverend Dr. Martin Luther King, Jr. spoke these words at the second convention of the Medical Committee for Human Rights in Chicago, Ill. These words still ring true today in 2022 as so painfully illustrated by the COVID pandemic that highlighted the differences in morbidity and mortality rates in historically minoritized communities. As pharmacologists and educators who are training the next generation of scientists and clinicians, we must acknowledge the bias and social determinants of health that impact the health and wellbeing of our country’s citizens. To bring these issues front and center, three speakers at EB 2022 unpacked concepts from different frameworks.

Speaker L’Aurelle A. Johnson, PhD, is an Assistant Professor in the Department of Experimental and Clinical Pharmacology at the University of Minnesota, College of Pharmacy. Her presentation explored Activating the DEIA Signaling Pathway through Pharmacology. Dr. Johnson spoke about the regulation of signal transduction pathways, which are complex and requires activation and inactivation of molecular pathways to elicit a desired response (i.e. cell proliferation, synaptic plasticity, long-term potentiation). Similarly, activating the Diversity, Equity, Inclusion, and Accessibility (DEIA) signal transduction pathway is a complex process, especially in the areas of activating people, education, and research. Effective activation of these signal transduction pathways requires: 1) reception, which is the detection and interaction between the signaling molecule or ligand with the specific receptor, 2) transduction, which is when the binding of the ligand to the receptors which initiates a sequential modification to downstream molecules that result in 3) a response, which is the outcome from a specific signal trigger. Dr. Johnson emphasized that people are important to the pharmacology enterprise and that diversity in people is important to ensure the perpetuity of the

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pharmacology enterprise. Despite people being the primary ligand to activate its receptor, she explained, there are systemic antagonists of microaggressions - biases, stereotype threats - that prevent people from getting into the enterprise and being successful in the enterprise. However, once people get into the enterprise, there are several factors that result in people being innovative and having increased productivity and purpose in the pharmacology enterprise. Dr. Johnson outlined three key positive regulators—practicing cultural competence, effective conflict management styles, and the enterprise valuing difference and respecting difference. She also stressed that education is critical to the pharmacology enterprise and is the foundation of accruing and disseminating knowledge to the scholarly communities. Despite education being the primary ligand to activate its receptor there is the systemic antagonist of standardized testing that prevents people from getting into pharmacology graduate education. However, once people get into graduate programs, educators need to practice inclusive teaching, ensure that an anti-racism curriculum is employed and that the program graduates are competent in the disciplines that one chooses to explore. Dr. Johnson noted that positive regulators of this desired response include adapting teaching methodologies to the various learning styles, honoring accommodations and respecting neurodiversity. The absence of these strategies serves as negative regulators of these responses. Dr. Johnson pointed out that research is how the pharmacology enterprise makes novel discoveries to yield change. Many positive influencers of research, such as collaborations, lab climate and mentorship result in increased publications, research funding, evidence-building innovation and leadership development are important. Conversely, poor experiences in any of these areas may negate the desired response, she explained. Crosstalk is when one or more of these pathways affects another, Dr. Johnson explained. In activating the DEIA pathway through pharmacology, the receptors of people, education, and research not only affect their individual pathways, but they also affect one another. For example, she said, negative regulators of people, such as microagressions and bias, also serve as negative regulators of education and research. In

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summary, by using the fundamental concept of signal transduction, we 1) highlighted how pharmacology intersects diversity, equity, inclusion, accessibility (DEIA) 2) explored the process of DEIA reception, transduction, and response in the area of people, graduate education, and research, and 3) explored the benefits/purpose of activating this pathway which fosters a scientific community that is innovative, discipline competent, welcoming and produces the next generations of pharmacology leaders. She asked attendees, “What steps are you going to take ensure that you activate the DEIA pathway People, Education, and Research within your institution?” Wilson M. Compton, MD, MPE. Deputy Director, National Institute on Drug Abuse, National Institutes of Health, Bethesda, Md., presented Advances in Research in Substance Use Disorders—Ensuring Equity. Substance use disorders are essentially geneticenvironmental-developmental conditions. Influential environmental factors include not only substance exposures themselves, but also characteristics of an individual’s family, neighborhood, school, and cultural contexts, Dr. Compton explained. Evidence regarding these environmental influences arise from both observational and experimental studies. He shared an example of a study done in rural Georgia that found a strong correlation between the number of teen years in poverty and diminishments by the early 20s in volume of brain structures that contribute to academic functioning, social development, learning, memory, mood, and stress reactivity. In contrast, those volumetric declines were not seen in the group whose families had received an experimental family-focused intervention when they were in early adolescence. Dr. Compton noted that in response to national developments and research, NIDA has launched its Racial Equity Initiative, which focuses on three major domains: 1) enhancing the diversity of the overall addiction scientific workforce, 2) addressing internal inequities within NIDA’s own operations, and 3) health disparities research to ameliorate inequity in prevention and treatment care. One recent research accomplishment is the documentation of perceived racism and discrimination among 10-11-year-old children in the NIH Adolescent Brain Cognitive Development study. Other research has documented disparities in fatal drug overdoses which have disproportionately included American

Indian/Alaska Native persons, especially during the COVID pandemic. Dr. Compton stressed that social environmental factors such as racial and ethnic inequities are key determinants of addictive disorders/outcomes. Dr. Asa Radix, MD, PhD, MPH. Director of Research and Education, Callen-Lorde Community Health Center, NY and Clinical Associate Professor, Columbia University presented Clinical Practice Guidelines in Transgender Healthcare. Statistics show that more than one million transgender and gender diverse adults live in the U.S. Transgender persons often encounter widespread stigma and discrimination, including in healthcare settings. In addition, Dr. Radix affirmed that access to medical care may be limited as health care providers often lack knowledge of the unique health concerns of this population. Therefore, it is important for healthcare workers to become familiar with the clinical practice guidelines for transgender individuals, including the standards of care for hormonal therapy and other gender-affirming interventions, for those who request them.

Guidelines for practice from the World Professional Association of Transgender Health (WPATH) have been in existence since 1979. Guidelines have also been published by The Endocrine Society. Dr. Radix noted that gender affirming interventions have been shown to improve quality of life, enhance social functioning and reduce rates of gender dysphoria in transgender individuals. The approach to hormone therapy is to recreate the hormonal milieu aligned with gender identity and patient goals, he explained. Although treatment is safe when used according to accepted guidelines, adverse effects may occur, such as venous thromboembolism on estrogen therapy. Individuals should be carefully monitored by knowledgeable health professionals who are aware of hormone-related adverse effects as well as potential drug-drug interactions. Dr. Radix stressed that all healthcare workers should strive to become culturally competent and knowledgeable to ensure that the settings they work in are welcoming and affirming to transgender individuals.

The Guppy Tank Translational Science Pitch Showcase Submitted by Khalid Garman, MD/PhD and Mohamed Ghonim, PhD The Guppy Tank Translational Science Showcase is a novel symposium that was first introduced virtually during EB 2021 and held for the first time in front of a live audience during EB 2022. The event was developed and organized by the ASPET Young Scientists Committee (YSC) to provide trainees with an opportunity to craft and deliver captivating pitches that highlight the translational impact and commercial value of their innovative research. Three finalists—Drs. Jia Nong and Subhi Marwari from the University of Pennsylvania and Dr. Mohamed Ghonim from St. Jude Children’s Research Hospital—were selected from a pool of highly competitive applications to compete for the Best Pitch Award. Each finalist was offered travel support and one-on-one mentoring by industry-expert coaches including Dr. Janet Clark (National Institute of Mental Health), Dr. Pamela Hornby (Johnson & Johnson), and Dr. Ross Corriden (Neuron23).

Guppy Tank winner Dr. Jia Nong (center) with the keynote speaker, Dr. Nancy Stagliano (left), and one of the judges, Dr. Kyle Palmer (right).

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The competitive segment of the event was proceeded by a keynote talk by Dr. Nancy Stagliano (Chief Executive Officer and Chair at Neuron23), who shared her incredibly successful scientific career journey traversing drug development, innovation, and startup biotech venture capital financing. Her talk covered the hallmark components of a translational science pitch and offered practical tips to developing broad audience-tailored presentations. Following the keynote talk, each finalist had 10 minutes to present their pitch in front of a live audience and elite panel of judges including Dr. Kyle Palmer (Opertech Bio), Dr. Frank Leu (Pennovation Center and Thomas Jefferson University), and Dr. Prabha Swayam (Temple University).

Each pitch was followed by a five-minute Q&A session. Overall, all the finalists delivered phenomenal pitches and Dr. Jia Nong was selected to receive the Best Pitch Award for her pitch on nanomedicine as a novel therapeutic approach for the treatment of stroke. Despite being held on the last timeslot of the last day of EB2022, The Guppy Tank Competition was well-attended, and the audience feedback was overwhelmingly positive. The YSC expressed gratitude for the coaches, judges, and the Divisions of Translational and Clinical Pharmacology and Drug Discovery and Development for a successful event. All involved believe the event provided the foundation for future YSC-organized science pitch showcases.

(l to r) The following received the Scientific Achievement Awards at the 2022 ASPET Annual Meeting at Experimental Biology in Philadelphia: Jin Zhang, PhD, FASPET, University of California San Diego, Robert R. Ruffolo Career Achievement Award in Pharmacology; Des R. Richardson, PhD, DSc, Griffith University, Otto Krayer Award in Pharmacology; Morris J. Birnbaum, MD, PhD, Pfizer, Inc., Pharmacia-ASPET Award for Experimental Therapeutics; Krzysztof Palczewski, PhD, University of California, Irvine, Goodman and Gilman Award in Receptor Pharmacology; Margarita L. Dubocovich, PhD, FACNP, FASPET, The State University of New York at Buffalo, Julius Axelrod Award in Pharmacology; Mikel Garcia-Marcos, PhD, Boston University, John J. Abel Award in Pharmacology; Krishnaswami Ramabadran, PhD, E. Leong Way Emeritus Travel Award. ASPET is dedicated to recognizing the best research in, contributions to and accomplishments in all areas of pharmacology. Scientists from all over the world and at all career stages are eligible for ASPET’s various awards. Learn more about the specific eligibility details for each award at http://www.aspet.org/awards.

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EB 2022 WRAP UP EB 2022 BRAND GUIDELINES

All awardees were acknowledged at the end of the ASPET Business Meeting and Award Presentations.

The Diversity & Inclusion session featured the topic Responding to Microaggressions. Participants also joined roundtable discussions.

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ASPET’s young scientists showcased their research during Poster Sessions held on Sunday, Monday and Tuesday. More than 600 pharmacology posters were presented.

EB 2022 BRAND GUIDELINES

Division Day featured the latest research from young scientists and esteemed award winners, in ASPET’s divisions of pharmacology. Featured talks were held at 8:00 am and 1:00 pm on Monday, April 4. Later, Division Mixers allowed members to catch up with old friends, make news ones and meet the awardees!

Poster award recipients for each division received recognition at the Closing Networking Event on Tuesday evening.

ASPET President Peggy Gnegy highlighted the society’s commitment to diversity and inclusion, meeting plans for 2023 in St. Louis and long-term goals for society growth.

Volunteers participated in a Day of Service to Philadelphia at EB 2022, where they spent the day at Prevention Point, a nonprofit public health organization. The annual day of service began in 2009 as an opportunity to give back to the local community during the annual meeting.

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Call for 2023 Award Nominations ASPET is dedicated to recognizing the best research in, contributions to, and accomplishments in all areas of pharmacology. We encourage members to nominate deserving scientists to raise awareness of the outstanding work being done in our field. ASPET is strongly committed to providing opportunities to all its members regardless of race, color, age, gender, sexual orientation, gender identity or ability/disability. Nominations from and for members of marginalized and underrepresented communities are greatly encouraged. Who can submit a nomination? You must be an ASPET member to submit nominations.

Who is eligible to receive awards? Scientists, educators, and others who have impacted the field of pharmacology from all over the world, in all career paths and at all career stages are eligible for ASPET’s various awards. Learn more about the specific eligibility details for each award at http://www.aspet.org/awards.

How do I submit a nomination? To nominate someone or yourself, visit: http://www.aspet.org/awards. Review the award criteria and nomination requirements. Nomination forms can be accessed via the Awards Portal.

When are nominations due? The deadline for nominations is Thursday, September 15, 2022 at 5:00 PM EDT.

What happens after a nomination is submitted? Each nomination is reviewed by the members of a designated committee. Scores and rankings are given, and compiled results are discussed by the committee, leading to the final selection of the 2023 awardee.

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ASPET Scientific Achievement Awards JOHN J. ABEL AWARD IN PHARMACOLOGY This award is presented for original, outstanding research in the field of pharmacology and/or experimental therapeutics by a candidate who is younger than 45. Named after the founder of ASPET, the award aims to stimulate fundamental research in pharmacology and experimental therapeutics by young investigators.

JULIUS AXELROD AWARD IN PHARMACOLOGY This award is presented for significant contributions to understanding the biochemical mechanisms underlying the pharmacological actions of drugs and for contributions to mentoring other pharmacologists. It honors 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.

ROBERT R. RUFFOLO CAREER ACHIEVEMENT AWARD IN PHARMACOLOGY This award honors the scientific achievements of scientists who are at the height of their careers (typically mid-to late-career) and who have made significant contributions to any area of pharmacology. It recognizes the contributions made to drug discovery and development by Dr. Ruffolo.

PHARMACIA-ASPET AWARD IN EXPERIMENTAL THERAPEUTICS This award 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.

REYNOLD SPECTOR AWARD IN CLINICAL PHARMACOLOGY AND TRANSLATIONAL MEDICINE This award recognizes excellence in research and/or teaching in clinical pharmacology. It was established in recognition of Dr. Spector’s dedication and contributions to clinical pharmacology and is made possible by the generosity of Dr. Reynold and Mrs. Michiko Spector.

Are you an ASPET emeritus member in need of travel funding to attend the ASPET 2023 Annual Meeting? E. LEONG WAY EMERITUS TRAVEL AWARD The E. Leong Way award provides financial support to defray the expenses for an ASPET emeritus member to attend the ASPET Annual Meeting. The award honors Edward Leong Way (1916-2017), who is remembered for his contributions to drug metabolism research, opioid pharmacology, and a western understanding of Chinese traditional medicine, as well as the numerous scientists he mentored over 75 years of his professional life. Self-nominations are permitted.

ASPET DivisionSponsored Awards

NORMAN WEINER LECTURE

EARLY CAREER AWARDS

The Norman Weiner Lecture was established in memory of Dr. Norman Weiner, past ASPET President and chair of the department of pharmacology at the University of Colorado. It is in honor of his many contributions to both ASPET and to pharmacology research and education. The award lecturer is selected by the ASPET Program Committee. Outside nominations are not being accepted.

Division-sponsored early career awards are intended for ASPET members who are past the postdoc or trainee career stage but still early in their careers (no more than 15 years after receiving their doctorate). Applications and nominations are welcome from members in academia, industry, government, or other organizational affiliations.

DAVID LEHR RESEARCH AWARD This award is intended to extend funding for preclinical or clinical research directed toward improving human health. This award is made possible by an endowment to ASPET from Mrs. Lisa Lehr in honor of her husband, the late Dr. David Lehr, former chair of the Department of Pharmacology of New York Medical College. It includes two years of funding at $50,000 per year.

Sponsored by the ASPET Division for Behavioral Pharmacology The JH Woods Early Career Award in Behavioral Pharmacology recognizes outstanding original research by early career investigators in behavioral pharmacology. Sponsored by the ASPET Division for Cardiovascular Pharmacology The Benedict R. Lucchesi Young Scientist Travel Award in Cardiac Pharmacology honors Dr. Lucchesi’s lifelong scientific contributions to our better understanding and appreciation

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of the pharmacological treatment and prevention of cardiovascular disease and for his mentoring of countless prominent cardiovascular pharmacologists in translational approaches. The award recognizes a member early in their career whose research interest is related to cardiovascular pharmacology. Sponsored by the ASPET Division for Drug Metabolism and Disposition The Richard Okita Early Career Award in Drug Metabolism and Disposition recognizes excellent original research by early career investigators in drug metabolism and disposition. Sponsored by the ASPET Division for Molecular Pharmacology The Division for Molecular Pharmacology Early Career Award recognizes scholarly achievements of investigators early in their independent careers in molecular pharmacology. Sponsored by the ASPET Division for Neuropharmacology The Division for Neuropharmacology Early Career Award recognizes and honors a young independent investigator who is working in any area of neuropharmacology. Preference is given to candidates who hold an independent position. An independent position is considered to be one that is responsible for securing and administering their own budgets for research (traditionally a faculty position, or a team leader in a non-university setting). Sponsored by the ASPET Division for Pharmacology Education Pharmacology Educators Awards defray costs to participate in the ASPET Annual Meeting. They are available for pharmacology educators who have relatively less experience as a pharmacology educator and/

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or junior faculty members (e.g., assistant professor). In addition to promoting participation in the ASPET meeting by pharmacology educators, this award is intended to foster career development in pharmacology education. Applicants must have significant teaching responsibilities in pharmacology, either graduate, undergraduate college classes, or professional schools. Sponsored by the ASPET Division for Toxicology The Division for Toxicology Early Career Award recognizes excellent original research by early career investigators in toxicology.

Sponsored by the ASPET Division for Translational and Clinical Pharmacology The Division for Translational and Clinical Pharmacology Early Career Awards recognize excellence in translational and clinical pharmacology research that comes from early career scientists. The purpose is to provide travel support to defray costs for two members to participate at the ASPET Annual Meeting.

Other Division-Sponsored Awards ASPET is strongly committed to providing opportunities to all its members regardless of race, color, age, gender, sexual orientation, gender identity, or ability/disability. Nominations from and for members of marginalized and underrepresented communities are greatly encouraged. Sponsored by the ASPET Division for Cancer Pharmacology The Susan B. Horwitz Award Lecture in Cancer Pharmacology recognizes excellent original research by established investigators in cancer pharmacology. The award honors Dr. Horwitz who has been a pioneer in understanding the mechanism of action of cancer chemotherapy drugs many of which have been and remain mainstays of cancer therapy.

Sponsored by the ASPET Division for Drug Discovery and Development The Scientific Achievement Award in Drug Discovery and Development recognizes outstanding investigators who have made significant contributions in drug discovery, translational and/or drug development science. This can include investigators who have developed technologies, methods or processes that have enhanced the process of drug discovery or enabled accelerated drug development. Contributions to any therapeutic area or therapeutic modality (small molecule, oligonucleotide, gene therapy, biologic or drugdevice combination) will be considered.

Sponsored by the ASPET Division for Pharmacology Education Pharmacology Educators Awards defray costs to participate in the ASPET Annual Meeting, are available for pharmacology educators at all career levels who are faculty members. Applicants must have significant teaching responsibilities in pharmacology: either graduate, undergraduate college classes, or professional schools.

Sponsored by the ASPET Division for Drug Metabolism and Disposition The James R. Gillette Awards are presented each year to two outstanding papers published in Drug Metabolism and Disposition, one each in the broad categories of a) drug metabolism and b) disposition and pharmacokinetics. No additional application is needed. All articles published in DMD 2022 issues will be considered.

Sponsored by the ASPET Division for Translational and Clinical Pharmacology The Ray Fuller Lecture was estabished to honor the achievements of Ray W. Fuller, PhD in applying an improved understanding of the central nervous system to discover better treatments for the mentally ill. Dr. Fuller was part of the team that discovered fluoxetine (Prozac), leading to an entire new approach to the therapy of depression. The award lecturer will be selected by the TCP division.

Sponsored by the ASPET Division for Neuropharmacology The Division for Neuropharmacology Diversity, Equity and Inclusion Recognition Award (DEI Recognition Award) is a new award that honors an individual who has made important contributions to the enhancement and promotion of diversity, equity and inclusion in the field of neuropharmacology. Applicant should have mentored, supervised or taught trainees from diverse, underrepresented backgrounds as defined by NIH.

Sponsored by the ASPET Division for Toxicology The Division for Toxicology Career Award recognizes outstanding original research contributions to toxicology by an established investigator.

Submit Your Nomination There is no better way to recognize someone who has made an impression on you and your career - submit your nomination by September 15, 2022. http://www.aspet.org/awards

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Meet the 2022-2023 Council ASPET's newly elected Council members start their new positions July 1, 2022. ASPET is governed by an elected council consisting of the President, the President-Elect and the immediate Past President (each serving for a one-year term in that elected office), the Secretary/Treasurer, the Secretary/Treasurer-Elect and the immediate Past Secretary/Treasurer (each serving a one-year term in that elected office), and three Councilors (each serving for a one-year term in that elected office, with one Councilor retiring each year). In addition to the elected members of Council, the Executive Officer, the chair of the Publications Committee, the chair of the Program Committee, the FASEB Board representative and an Inclusion, Diversity, Equity and Accessibility representative are non-voting ex officio members of Council during their terms in the respective offices.

Michael F. Jarvis, PhD, FBPhS

Namandjé N. Bumpus, PhD

Margaret E. Gnegy, PhD

President

President-Elect

Past President

Kathryn A. Cunningham, PhD

Xinxin Ding, PhD

Carol L. Beck, PharmD, PhD

Secretary/Treasurer

Secretary/Treasurer-Elect

Past Secretary/Treasurer

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Nina Isoherranen, PhD

Randy A. Hall, PhD

John R. Traynor, PhD

Councilor

Michael W. Wood, PhD

Catherine M. Davis, PhD

Kenneth Tew, PhD

Ex Officio Chair, Program Committee

Ex Officio FASEB Board Representative

Ex Officio Chair, Publications Committee

Get to Know ASPET’s Leadership Reach out and connect with ASPET’s Council members on ASPETConnect. https://connect.aspet.org

Marcia I. Dávila-Garcia, PhD

David Jackson

Ex Officio Inclusion, Diversity, Equity & Accessibility Representative

Ex Officio Executive Officer

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Lithium:

Battering Mania Rebecca J. Anderson, PhD While working as a prison warden’s administrative assistant in 1985, Risdon Slate began suffering from insomnia. Because the South Carolina prison had just performed a couple of executions in quick succession, Slate was diagnosed with “situational depression” by his family physician, who prescribed the antidepressant, amitriptyline (1, 2). In 1986, Slate took a job as a probation officer (1-3). After some stressful encounters with a parolee, he again experienced insomnia and began selfmedicating with alcohol (2).

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While in Miami for federal probation officer training, Slate got into an argument with a man at the hotel bar. Slate thought he was in an episode of the 1980s TV drama, Miami Vice, and that the man was an actor (1-3). When police arrived, Slate insisted on speaking only to Sonny Crockett, the central character in Miami Vice (3). Within two weeks, Slate resigned his job for medical reasons, and his wife announced she was divorcing him (1). A South Carolina psychiatrist finally got to the source of Slate’s problems. His diagnosis was bipolar

disorder, and he told Slate that amitriptyline was the wrong medicine. Antidepressants exacerbate mania. “It’s like putting jet fuel on the fire” (1). Instead, he prescribed lithium.

Salt of the Earth Lithium is an alkaline metal. It was discovered in 1817 in mineral ore in Sweden. Although the name comes from lithos, the Greek word for stone, lithium is also found in seawater, mineral springs, and meteorites (4-6). There are also tiny amounts in both plant and animal matter (5). In 1818, scientists found that powdered lithium glows crimson red when ignited, making it a key ingredient in red fireworks (4, 5). Its chief use today is in electronics and lithium-ion batteries, but it has long been used in medicine. In 1859, Alfred Baring Garrod reported using lithium carbonate as a remedy for gout (7-9). If blood uric acid is high (for example, from eating purine-rich foods like meat and fish), uric acid crystalizes in the joints causing pain, and, in the kidneys, forming stones. The idea behind Garrod’s treatment was that lithium salts are very soluble and could dissolve the uric acid

deposits around gouty joints (10, 11). Physicians came to believe that excess uric acid was responsible for many other maladies, and they prescribed lithium as the treatment (7, 10). When lithium was discovered in mineral springs, people sought those natural waters to cure rheumatism, diabetes, asthma, and other ailments, as well as gout. Among the high-profile spas in the US was Lithia Springs, Georgia, whose clientele included the Vanderbilts, Mark Twain, and Presidents Cleveland, Taft, McKinley, and Theodore Roosevelt (7). In 1894, the Danish brothers Carl and Fritz Lange reported favorable results using lithium carbonate in 35 patients with mild depression. They attributed their success to the alleged effect on uric acid (7-10). Interestingly, they chose doses of lithium that are comparable to those currently used for bipolar illness (7). The Lange brothers published in Danish, later translated only into German. So, few practitioners outside of Denmark knew about their work. Even in Denmark, doctors discounted the results, because by then, studies had shown that ingesting lithium had no effect on uric acid (6, 7, 10).

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7-Up Lithium beer was brewed and marketed in Wisconsin (4, 7). In 1929, a patent medicine called “BibLabel Lithiated Lemon-Lime Soda” was introduced as a mood booster and cure for hangover (4, 7, 8). Lithium citrate was one of its seven ingredients, and in 1936, the name was shortened to 7-Up (6, 7). By the mid-20th century, the medical community had discarded lithium as a credible treatment for anything, and the US Food and Drug Administration (FDA) banned lithium from beer and soft drinks (6, 7). Re-introducing lithium as a bona fide medicine took the valiant efforts of a free-spirited Australian and a persistent Dane.

Common Cause From an early age, John Cade and Mogens Schou were familiar with mentally ill patients. Their fathers

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were both psychiatrists. The Cade family’s home was on the grounds of Mont Park Hospital for the Insane, where the senior Cade was superintendent. Schou’s father was director of two psychiatric hospitals in Denmark, and several of his relatives suffered from mental illness (6, 7, 12). In the 1930s, Cade and Schou followed their fathers and became physicians. Their training included Emil Kraepelin’s seminal Compendium of Psychiatry. Kraepelin, widely regarded as the founder of modern psychiatry, developed a method for classifying psychiatric disorders that is still used today (7). In the second volume of his Compendium, he described “manic-depressive insanity,” which was later renamed manic-depressive illness, and more recently, bipolar disorder (6). Many treatments for mental illness were tried, mostly with minimal success. Insulin-induced comas could temporarily alleviate schizophrenia

Australian psychiatrist John Cade discovered the use of lithium as a treatment for bipolar disorder.

assaults. But Cade investigated the bruises methodically from a medical perspective, rather than psychiatry, and found a lack of vitamin C in the patients’ diet (6, 7). Further review of patients at Beechworth and Mont Park Mental Hospital, where his father was superintendent, revealed that scurvy from lack of vitamin C was widespread (6, 7). Through Cade’s efforts, fresh fruits and vegetables were added to the meals at all of the mental hospitals in the state of Victoria.

Changi POW

symptoms but were less effective in manic-depressive illness, especially in the depressed phase (7). Electroconvulsive therapy (ECT), introduced in 1938, calmed patients suffering from mania and shortened attacks of depression. ECT remains an effective treatment for depression, but it does not prevent future attacks, which require repeated ECT (7, 9, 13). Cade and Schou were also familiar with Freudian psychoanalysis, the prevailing dogma at the time. But they both sought biochemical causes of mental illness (6). If biochemical abnormalities could be identified, then it might be possible to find truly effective pharmacological treatments.

Cade’s Journey After graduating from medical school, Cade was appointed medical officer at Beechworth Mental Hospital (6). In parallel, he pursued postgraduate work for an MD. At that time in Australia, the MD was analogous to a PhD and meant for doctors wishing to pursue clinical research (6, 7). The graduate work required in-depth knowledge of physiology, pathology, immunology, and clinical medicine, including the history of medicine. One of Cade’s first research efforts,albeit observational, was investigating the extensive bruising on some of the patients at Beechworth. Others might have dismissed this as unnecessary force by the staff or patient-inflicted

Cade received his MD in 1938 and simultaneously moved to Bundoora Repatriation Mental Hospital as a junior medical officer. Unfortunately, his plans to continue research were interrupted in 1939 when Australia entered World War II. Although Cade was married with two sons, he enlisted and was posted to the 2nd/9th Field Ambulance as a captain (6, 7). Shortly after his unit’s arrival on the Malay Peninsula, Cade was promoted to major. When Japan invaded Malaya, Cade, along with thousands of Australian and British troops, became prisoners of war (POWs) at Changi prison camp on the island of Singapore (6, 14). Officially, Cade was a regimental medical officer, but because of his experience with mental illness, he was put in charge of Changi’s small psychiatric ward. He also consulted on psychiatric cases in the general hospital wards. The troops affectionately called him the “Mad Major” (6, 7). Cade did his best to treat a wide range of problems with limited resources. The meager rice rations caused many cases of beriberi, pellagra, and painful rashes. Cade and his medical colleagues devised several concoctions, attempting to provide essential vitamins, and conducted controlled studies to assess their relative benefits. A local grass proved to be rich in riboflavin, and they used it to make a bitter, light orange soup. The men called it Tiger’s Piss (6, 7). Cade’s views on mental illness were profoundly influenced by his experiences in Changi (6). He kept detailed records, and when patients who had exhibited apparent mental illness died, he conducted autopsies. A manic soldier had suffered a massive subdural hematoma. In an uncoordinated hysterical sergeant, Cade saw extensive loss of myelin in the central nervous system (6, 7).

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Cade was probably wrong when he thought guinea pigs were tranquilized by lithium. But he saw something remarkable, and his nimble mind concluded that lithium was worth pursuing—in patients.

Cade found psychoanalysis of limited value. He once defined it as “the art of describing the commonplace in terms of the incomprehensible” (7). Many of the POWs were demoralized and distressed, but stress alone did not seem to cause mental illness. And trying to alter psychiatric symptoms with psychoanalysis was an “absolute failure” (6). This, along with his autopsy results and the nutrition experiments, convinced Cade that mental illness resulted from an underlying biological or physical problem. “I could see that so many of the psychiatric patients suffering from the so-called functional psychoses appeared to be sick people in the medical sense. This fired my ambition to discover their etiology” (7). Despite the horrors of Changi, Cade did everything he could to protect his men and keep up their morale. His colleagues admired his medical and psychiatric expertise. The troops held him in high regard for his level-headedness, resilience, courage, honesty, and compassion (7). Formerly robust and athletic, Cade returned from Changi in 1945, after three and a half years as a POW, weighing about 90 pounds (7, 14). He was frustrated at the lost time away from his family and profession. He told his wife:“The old brain box is simmering with ideas. I believe this long period of waiting has allowed many of my notions in psychiatry to crystallize, and I’m just bursting to put them to the test. If they work out, they would represent a great advance in the knowledge of manic-depressive insanity and primary dementia” (7).

Testing Urine After a few months’ recuperation, Cade returned to Bundoora Repatriation Mental Hospital and lived with

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his family in a house on the hospital grounds (6, 14). Most of his patients were ex-soldiers. He was a prodigious reader, and his now-classic experiments began with reading Recent Advances in Endocrinology (6). He was intrigued by the effect of thyroid hormones on behavior. An overactive thyroid gland can cause agitation and restless thought. An underactive thyroid causes sluggishness, impaired memory, and depression. This reinforced his notion that brain function should be viewed biochemically (6). He had already seen psychological changes in his patients due to vitamin deficiencies, and his autopsies revealed pathologies in the brains of mentally disturbed POWs. Cade speculated that an excess of some unknown chemical made patients manic, and perhaps a deficiency of this same chemical caused depression (6, 7). Because he had limited resources, he began by examining urine, looking for excess of some chemical component in manic patients (15). He worked in his garage, but as the jars of urine accumulated, he looked for better facilities. Fortunately, there was an empty pantry in a ward that had just been built but not yet occupied (6). It had a bench, sink, and hot and cold water but no refrigeration. Cade stored the jars of urine on the top shelf of the family’s refrigerator, and he set up his guinea pig pens in the family’s garden (6, 7). Cade injected guinea pigs with the patients’ urine in stepwise amounts to determine the lethal dose. Large volumes of urine always killed the guinea pigs, but he found that urine from the manic patients was particularly toxic (6, 7, 10). This turned out to be false. The urine of manic patients is actually no more lethal than any other sort of urine (6). But this observation spurred him to continue. Next, he tried to determine the substance in urine that was responsible for toxicity. Of urine’s major components, urea seemed to kill the guinea pigs similar to whole urine. Unfortunately, the urine from his manic patients contained no more urea than the urine from other patients (6, 7, 10). In a somewhat illogical leap, he then imagined that some other chemical might be enhancing the toxicity of urea. Of the chemicals he tested, uric acid slightly enhanced urea’s toxicity. Unfortunately, he could not complete the dose-response curve, because uric acid is only sparingly soluble in water (3, 6, 7, 10). To

overcome this, he switched to lithium urate, the most soluble salt of uric acid.

A Right from Two Wrongs To his surprise, lithium urate reduced the toxicity of urea (3, 7, 10). So, he repeated the experiment using lithium carbonate, to see if lithium might be responsible for this unexpected finding (3, 10). An 8% solution of urea caused five of ten guinea pigs to die. When he added lithium carbonate to the urea solution, all ten guinea pigs survived (15). In his next experiment, Cade tested the effect of lithium carbonate alone. Guinea pigs have a robust startle response. But after injecting lithium carbonate, he could turn them on their backs, and instead of their usual frantic righting reflex, they merely lay there placidly (15). Later, other investigators were unable to reproduce Cade’s results unless they injected animals with large, toxic doses of lithium. Rather than a beneficial tranquilizing effect, Cade’s guinea pigs were probably showing early signs of lithium poisoning (6, 7). Cade was wrong when he concluded that urine from manic patients was more toxic than other urine. He was also probably wrong when he thought guinea pigs were tranquilized by lithium. But he saw something remarkable, and his nimble mind concluded that lithium was worth pursuing, in patients (6, 7).

Clinical Proof After ingesting lithium himself to ensure that it was safe, Cade began his groundbreaking clinical studies (3, 10). The first subject was Bill Brand, a 51-yearold man who had suffered manic-depressive illness for 30 years. He had been admitted to Bundoora in September 1943 and was considered the most troublesome patient on the ward (15). Initially, Bill responded well to ECT treatment, but after a few months his mania returned. Repeated ECT had no effect (6). By the start of 1948, Bill was in a more-orless continuous manic state (15). On March 6, 1948, Cade noted that Bill’s blood uric acid was “extremely high,” which he used to justify lithium treatment (6). On March 29, 1948, Cade began administering lithium citrate, using the historical literature on the treatment of gout to guide his dose selection (15). Within days, Bill was noticeably quieter, and he steadily improved. Because lithium citrate caused nausea and

BIPOLAR DISORDER Typically, bipolar disorder first appears in late adolescence or early adulthood. Manic episodes might last for days, weeks, or months. The person might experience recurring manic episodes or, just as likely, plummets into a profound state of depression and despair. Between episodes, the person is perfectly well and can function normally for months or years. But then, inevitably, another attack occurs. In untreated manic-depression, early death is common, and suicide rates are high.

vomiting, Cade switched to lithium carbonate. On July 9, 1948, Bill was discharged, perfectly well, with instructions to take a maintenance dose of 300 mg lithium carbonate, twice daily (15). Cade proceeded to treat nine additional manic patients with lithium. Many had been in and out of asylums their entire lives, and they all improved to some degree on lithium (15). Cade also administered lithium to six schizophrenic patients, but he saw “no fundamental improvement” (15). Three of them had been unusually restless, noisy, and shouting nonsensical abuse. During lithium treatment, they became quiet and agreeable, and Cade could discontinue their routinely prescribed doses of nighttime sedatives. When lithium treatment was stopped, they reverted to their previous schizophrenic state (15). Cade was concerned that lithium might precipitate a depressive episode in patients who suffered recurrent depression. But he saw no evidence of that (15). Cade conducted his animal and clinical studies alone (6). But he did discuss his findings with colleagues at medical meetings, and he published his results in September 1949 (15).

A Salty Setback Cade’s unprecedented results sparked curiosity, interest, and excitement among Australian psychiatrists (6). Some of them began treating their manic patients

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with lithium. But his work received no notice beyond Australia, neither accolades nor criticism, for two reasons. First, Cade published his findings in the Medical Journal of Australia, which was not widely circulated outside of Australia. So, the global medical community was largely unaware of his findings. Second, and more impactful, were new reports of lithium toxicity, which were published concurrently in the US (5, 16). In the late 1940s, doctors advised patients who suffered from hypertension to cut their salt consumption. Low-sodium diets are bland, and US companies devised alternatives to table salt that would satisfy the patients’ desire for a salty seasoning without increasing blood pressure (6, 7). At least four manufacturers came up with lithium chloride, which they marketed quite profitably in the US (6). In March 1949, four papers appeared in JAMA suggesting that the lithium salt substitutes were toxic. From the time of Garrod and the treatment of gout, the narrow therapeutic window of lithium was well-known. Lithium can disturb thyroid activity and interfere with kidney function, leading to kidney failure (3, 7). High doses cause nausea, vomiting, and tremors, leading to seizures, coma, and death (7). In general, using lithium chloride as a salt substitute was not harmful (5). But excessive consumption could be dangerous, especially in patients with comorbidities, such as congestive heart failure or cerebral arteriosclerosis. Patients on a low-sodium diet seemed to be especially susceptible to lithium toxicity (5, 11, 16). Collectively, the JAMA reports described only 16 case histories (6). The three patients who died had consumed excessive amounts of lithium chloride, but widespread news coverage amplified the issue and caused a public outcry (6, 7). The FDA advised consumers to “Stop using this dangerous poison at once,” and US manufacturers withdrew their salt substitute products (6, 8, 11).

Cade’s Caution When Cade submitted his 1949 paper, he may not have been aware of the publicity in the US, but he was certainly aware of lithium’s side effects. His paper reported his observations of abdominal pain, anorexia, nausea, vomiting, mild diarrhea, giddiness, tremors, ataxia, slurred speech, and muscle twitches (15). He advised close monitoring of patients and adjusting the lithium dose accordingly.

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The FDA advised consumers to “Stop using this dangerous poison at once,” and US manufacturers withdrew their lithium salt substitutes.

Bill Brand’s case exemplified how difficult it was to maintain a patient within that narrow therapeutic window. After Cade’s paper appeared, Bill’s manic episodes re-emerged, and Cade increased the lithium dose, which caused burning abdominal pain and nausea. Stopping treatment eased the side effects, but Bill relapsed (6). For months, Bill and Cade were at odds, vacillating between higher doses of lithium (which controlled Bill’s mania but caused great discomfort) and stopping treatment (which eased the side effects but triggered a relapse). Cade’s final round of treatment in the spring of 1950 was a massive 2.6 grams of lithium three times daily (6). It calmed Bill’s manic symptoms, but he lapsed into a semi-coma and had three seizures (7). Bill died on May 23, 1950 (6, 7). There was no autopsy, but Cade reported to the coroner that Bill’s death was due to a combination of lithium toxicity and chronic mania (6). A handful of Australian psychiatrists (mostly at longterm mental hospitals) were successfully treating their manic-depressive patients with lithium. But around the same time as Bill’s death, they reported that two additional Australian patients had died from lithium toxicity (6, 7). Those patient deaths, along with the salt substitute cases in the US, convinced Cade that lithium’s potential for harm outweighed its benefits, and he stopped using it (7). In 1952, Cade became superintendent at Melbourne’s prestigious Royal Park Mental Hospital, and he banned lithium’s use there. He conducted no further research on lithium, but he actively solicited and compiled reports from psychiatrists on the efficacy and toxicity of lithium (7).

Flaming Success Among the Australian clinicians who were successfully treating patients with lithium were Edward

Trautner and Charles Noack (6, 7). Trautner, a refugee lithium. Because of diligent blood level monitoring, no from Nazi Germany, had earned his medical degree in lithium-related deaths were reported in the Australian Berlin and obtained an appointment in the physiology state of Victoria after 1953 (6). department at the University of Melbourne. He was a Schou’s Journey scientific polymath with research expertise ranging from Meanwhile, in Denmark, Erik Strömgren, the head animal and plant physiology to brain biochemistry (7). of Aarhus University’s Risskov Psychiatric Hospital, Noack, a new psychiatrist at Melbourne’s Mont Park had seen Noack and Trautner’s paper. He referred the Hospital and a former student of Trautner’s, had seen paper to Mogens Schou, who had recently arrived at Cade’s paper and was interested in trying lithium. the clinic as a research associate and was looking for Noack asked Trautner for advice, and together they a biological research topic (7, 10, 12). conducted a clinical study (7). Schou received his medical degree from They gave lithium to over 100 psychiatric patients, the University of Copenhagen in 1944 and then including more than 30 with mania (7). Mindful of served residencies in clinical psychiatry at several lithium’s toxicity and the recent lithium fatalities, Scandinavian hospitals (7). In addition to Trautner’s Trautner arranged for blood level measurements. work, Schou soon found Cade’s paper, and he was Victor Wynn, a research fellow in the physiology impressed with the lithium results. But the Australian department, had developed a method for accurately authors merely described observational cases. Schou measuring potassium, sodium, and calcium levels and Strömgren realized that a randomized, placebousing flame photometry, a new technology at the time. controlled clinical trial was Trautner asked Wynn to use his still lacking (7, 10, 12). flame photometer to measure Their study, published lithium in the patients’ blood in 1954, was the first samples (7). Schou’s study, controlled trial of lithium Noack and Trautner’s in mania, and perhaps, the published in 1954, results, which were published first randomized controlled in August 1951, were consistent was the first clinical trial in psychiatry with Cade’s findings. controlled trial of (7). They treated 38 manic Thanks to their blood level patients and measured lithium in mania, measurements, they could lithium blood levels (11). define the therapeutic window, and perhaps, the Their results were consistent which they reported to be first randomized with the Australian reports. between 0.6 and 1.2 mEq/l (7, Similar to Trautner’s findings, controlled clinical trial 17). None of their patients died Schou found the therapeutic or developed serious toxicity. in psychiatry. window to be between 0.5 Blood level monitoring was and 2.0 mEq/l (11). a major breakthrough. Doctors Like Cade, Schou could now titrate the therapeutic collected information and dose of lithium. reprints about lithium and maintained a database. Following Noack’s study, Trautner teamed with But unlike Cade, Schou continued clinical trials with Samuel Gershon to conduct a series of clinical studies lithium, which was the focus of his research for the (6, 7, 17). Polish by birth, Gershon was educated in rest of his career. Because of the stability of the Australia, including a residency in psychiatry and Danish population, he was able to follow his patients fellowships in physiology and pharmacology (17). for many years (12). By the end of 1952, Gershon and Trautner were administering lithium to patients at numerous hospitals Preventing Attacks around Melbourne. In the early 1960s, Schou received word from two At Royal Park Mental Hospital, Cade eased his investigators who, though working independently, had restriction and allowed his psychiatrists to dispense both observed that chronic lithium treatment seemed to

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Lithium soon became the prophylactic drug of choice worldwide. prevent recurrence of both manic and depressive episodes in bipolar patients (12). In his 1954 study, Schou described a patient in whom lithium had stopped outbreaks of both mania and depression, but he had not paid attention to the possible preventative action of the drug (7). Similarly, Cade had anecdotally described the benefits of continuous lithium treatment in Bill Brand and several other patients (14). But subsequently, psychiatrists focused on suppressing manic attacks, and no one had systematically studied the effects of lithium on depressive episodes (7). In view of these new reports, Schou decided to take another look. He collaborated with Poul Baastrup, a psychiatrist in Glostrup, Denmark. Over the next 6 years, they treated 88 bipolar and unipolar patients at Glostrup Psychiatric Hospital. During lithium treatment, the patients experienced markedly fewer manic and depressive episodes (12). Patients who stopped taking lithium suffered recurrences.

Best Buddies In late 1963, Schou sent a letter to John Cade (6, 7). He explained that his brother had suffered from unstable moods and had been in and out of mental asylums for 25 years. Every spring, he suffered an episode, which lasted for several months and rendered him unable to work. ECT and other drugs had failed, but within weeks of starting lithium treatment, he improved. Maintenance doses of lithium completely prevented the annual relapses, and he was functionally cured (6, 7). Schou’s clinical studies impressed Cade. Over the years, they developed a deep friendship and mutually praised each other’s work. They also hosted each other’s visits to Denmark and Australia (6, 7).

Countering Criticism Schou and Baastrup published their findings in 1967 (7). Soon, psychiatrists throughout Scandinavia and continental Europe were prescribing lithium as

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a prophylactic treatment, and they confirmed the Danish results (12). Unlike Schou’s 1954 study, the 1967 prophylaxis study had started on an exploratory basis and gradually grew, so it was not randomized or placebo-controlled (12). This left Schou and Baastrup open to criticism, and the harshest critics were Michael Shephard and Barry Blackwell at Maudsley Hospital in London. In the decades before evidence-based medicine, the Maudsley psychiatrists prided themselves on rigorous evaluation of alleged psychiatric treatments, and in fact, they had debunked a number of bogus treatments (6, 7). Although they never conducted lithium studies themselves, they published a harsh critique of Schou’s study in The Lancet in 1968 (13, 18). Shephard and Blackwell faulted Schou’s patient selection criteria, statistics, criteria for establishing prophylaxis, lack of blinding, and lack of placebo control (18). Those criticisms were justified, but the Maudsley group went further, accusing Schou of bias, because he had successfully treated his brother with lithium, making him a “believer” who lacked scientific objectivity (12). Schou and Baastrup acknowledged the deficiencies in their open-label, observational study. They followed up with a controlled trial, but they agonized over using a placebo control. They didn’t want to prolong patient suffering and possibly trigger suicides by withholding a drug that they were convinced was highly beneficial (19). They finally settled on a double-blind discontinuation protocol as the most ethical option. The study enrolled 84 women with manicdepressive disorder or with recurrent depressive disorder at Glostrup Psychiatric Hospital. All of them had been well-managed on lithium for at least a year (12, 19). Under double-blind conditions, the patients were randomized to either continue taking lithium or switched to placebo. Patients who relapsed during the trial were given lithium, without telling the observers or patient whether she had been in the lithium or placebo group. This protocol design exposed the fewest patients to placebo for the shortest time (12). The results were definitive. Of the 39 patients on placebo, 21 relapsed during the five-month trial, but none of the 45 patients in the lithium group relapsed (19). It was clear evidence that lithium prevented manic and depressive attacks. The study was published in 1970, and over the next few years, investigators in other countries confirmed

the findings using various protocol designs (12, 13). Lithium soon became the prophylactic drug of choice worldwide (12). Today, this preventative effect is recognized as lithium’s most important benefit (7).

FDA Approval By the mid-1960s, a number of European countries had approved lithium for manic-depressive illness (9). But the FDA lagged far behind, for two reasons. First, during and after World War II, a large number of European psychotherapists immigrated to the US. Some of them had been in Freud’s inner circle. They reinforced America’s general acceptance of psychoanalysis as the gold standard for treating almost all mental illnesses. Some therapists believed that drugs actually interfered with the psychoanalysis process (7). Second, FDA officials still remembered lithium toxicity from the salt substitute debacle, and lithium fell outside the usual procedure for drug approval. Lithium salts could not be patented and therefore offered no financial incentive to drug companies (7, 20). It was unclear who (if not a drug company) would file a New Drug Application (NDA) for lithium and what data it should contain (7). Also, the first effective drugs for schizophrenia (chlorpromazine) and depression (imipramine) had been discovered in the mid-1950s. Drug companies vigorously marketed them, and psychiatrists readily prescribed them (7). Despite the popularity of the new psychiatric drugs, a few psychiatrists remained lithium champions, including Samuel Gershon, who emigrated from Australia to the US in 1963 (17). As a Pfizer Fellow at the University of Michigan, Gershon and his colleagues

One lithium advocate cynically suggested that FDA officials granted approval simply to avoid having to process the flood of IND applications from individual psychiatrists.

bought kilograms of lithium from a chemical supply company for a trial funded by the National Institute of Mental Health (NIMH) (9). Because lithium was an investigational drug, psychiatrists could use it legally only by submitting an Investigational New Drug (IND) application to the FDA. INDs were meant for researchers who intended to conduct clinical studies, but most psychiatrists simply wanted lithium to give to their patients. Hundreds of other psychiatrists formed a sort of “lithium underground,” prescribing it without bothering to file an IND (7, 9). By the end of the 1960s, clinical reports on lithium were appearing in the American medical literature, and the American Psychiatric Association set up a lithium task force, including Gershon, to prepare prescribing recommendations (7). Gershon and others also lobbied the NIMH, FDA, and anyone else who would listen, pushing for general lithium availability (4, 7). The American College of Neuropsychopharmacology (serving as the sponsor) began preparing an NDA for lithium. This became unnecessary when Pfizer and a small pharmaceutical company, Rowell Laboratories, submitted their own regulatory applications (7, 20). They gathered enough data, with the assistance of Gershon and four other psychiatrists, to show that lithium was effective in bipolar disorder and (with blood, thyroid, and kidney monitoring) was safe (4). In 1970, the US became the 50th country to approve lithium for mania (3, 9, 10). One lithium advocate cynically suggested that FDA officials granted approval simply to avoid having to process the flood of IND applications from individual psychiatrists (7). In 1974, on the strength of a large US study, the FDA extended its approval of lithium to include prophylactic treatment of recurrent manic-depressive illness (7, 9, 12). The FDA’s approval served as an endorsement and convinced clinics around the world to administer lithium. Research, publications, and treatment of manicdepressive illness with lithium skyrocketed (6, 7).

Recognition Although some called Cade’s discovery serendipitous, Schou always defended his friend. “To make therapeutic discoveries on the basis of misinterpreted experiments,” he said, “required curiosity, daring, luck, and compassion for the patients” (7). Cade and Schou both lectured extensively on lithium to general practitioners, psychiatrists, hospital

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Despite lack of drug company advertising, the constant introduction of vigorously promoted but less effective psychiatric drugs, and the perception that lithium is tricky to use, research on lithium continues to affirm its unique value.

physicians, and patient groups worldwide and received numerous awards (12). In 1974, Cade and Schou shared the world’s richest prize in psychiatry, the International Kittay Scientific Foundation Award (6, 7). In 1987, Schou received the Lasker Award in Clinical Medical Research for his lithium work.

Stopping Suicide Manic-depressive patients are 10 to 20 times more likely to kill themselves than the general population (7, 21). Depression poses the greatest risk, but impulsivity, agitation, and aggression are also contributing factors. These patients also suffer high rates of alcoholism and substance abuse and a higher death rate from natural causes, particularly cardiovascular disease (7). As psychiatrists conducted further clinical studies, they found that lithium-treated patients were 10 to 15 times less likely to attempt or complete a suicide (7, 8, 12). Although individual study results vary, a recent meta-analysis of clinical data from the past

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40 years concluded that “the evidence to date is overwhelmingly in favor of lithium as an antisuicidal agent” (22). No other psychiatric drug has demonstrated this anti-suicidal effect (3, 7, 12).

Other Treatments Despite its superior efficacy and low cost, only about 10% of American bipolar patients take lithium. In the mid-1980s, psychiatrists began prescribing the anticonvulsant, valproate, off-label (7, 0). Later, clinical trials showed that valproate was effective in alleviating mania and preventing manicdepressive episodes. It was less effective than lithium and does not appear to have lithium’s anti-suicide effect. But it has a wider safety margin and does not require blood, thyroid, and kidney monitoring (7). The FDA approved valproate for bipolar disorder in 1995 (7, 9). Like several other anticonvulsants, valproate can cause fetal abnormalities, but it was aggressively marketed for bipolar disorder and became more widely used in the US than lithium. Despite lack of drug company marketing, the constant introduction of vigorously promoted but less effective alternative drugs, and the perception that lithium is tricky to use, research on lithium continues to affirm its unique value (7).

“Recovery is possible” Risdon Slate took lithium for 30 years and relapsed only once, when he was taken off lithium for 2 months (1). He married again, got a job teaching at a community college, and earned his PhD in criminal justice. He is currently a criminology professor at Florida Southern College, advocates for the decriminalization of mental illness, and helps to train law enforcement officers in skills for compassionately managing those in mental crisis. He recently switched to valproate, because his kidney function was worsening. But he says, “Lithium saved my life” (1).

References 1. Risdon Slate, personal communication, March 15, 2022. 2. Moore KC (November 28, 2021) Mental health: after personal struggles, criminology professor advocates for decriminalizing mental illness. The Ledger; available from: https://www.theledger.com/story/news/regional/2021/11/28/ florida-southern-college-professor-advocates-for-decriminalizing-mentalillness/8666060002/. 3. Halford B (2013) Limits of lithium. Chem Eng News 91(12): 15-20. 4. Lowe J (June 25, 2015) I don’t believe in God, but I believe in lithium. New York Times; available from: https://www.nytimes.com/2015/06/28/magazine/i-dontbelieve-in-god-but-i-believe-in-lithium.html. 5. Hanlon LW, Romaine III M, Gilroy FJ, and Deitrick JE (1949) Lithium chloride as a substitute for sodium chloride in the diet. JAMA 139(11): 688-692. 6. De Moore G and Westmore A (2016) Finding sanity: John Cade, lithium and the taming of bipolar disorder. Allen & Unwin, Sydney, Australia. 7. Brown WA (2019) Lithium: A doctor, a drug, and a breakthrough. WW Norton & Company, New York. 8. Cousins DA, Squarcina L, Boumezbeur F, Young AH, and Bellivier F (2020) Lithium: past, present, and future. Lancet Psychiatry 7(3): 222-224. 9. Shorter E (2009) The history of lithium therapy. Bipolar Disord 11(Suppl 2): 4-9. 10. Mitchell PB and Hadzi-Pavlovic D (2000) Lithium treatment for bipolar disorder. Bull World Health Organ 78(4): 515-517. 11. Schou M, Juel-Nielsen N, Strömgren E, and Voldby H (1954) The treatment of manic psychoses by the administration of lithium salts. J Neurol Neurosurg Psychiatry 17: 250-260. 12. Schou M (2009) My journey with lithium, in: History of the introduction of lithium in to medicine and psychiatry. Birth of modern psychopharmacology (Schioldann J ed.) pp. 312-320, Adelaide Academic Press, Adelaide, Australia; available from: https://inhn.org/biographies/mogens-schou-my-journey-withlithium.html. 13. Grof P (2006) Mogens Schou (1918-2005). Neuropsychopharm 31: 891-892. 14. Cade JF (June 2012) Discovery and the use of lithium. Univ. of Melbourne Collections, Issue 10; available from: https://museumsandcollections.unimelb. edu.au/__data/assets/pdf_file/0008/1379006/03_Healy-Medical10.pdf. 15. Cade JF (1949) Lithium salts in the treatment of psychotic excitement. Med J Aust 2(10): 349-351. 16. Corcoran AC, Taylor RD, and Page IH (1949) Lithium poisoning from the use of salt substitutes. JAMA 139(11): 685-688. 17. Ban TA (2011) Neuropsychopharmaoclogy - Samuel Gershon, in: An oral history of neuropsychopharmacology: the first fifty years (Ban TA ed.) pp. 19-34, American College of Neuropsychopharmacology, Inc., Brentwood, TN; available from: https://acnp.org/wp-content/uploads/2017/10/Volume1.pdf. 18. Blackwell B, Cantab MD, and Shepherd M (1968): Prophylactic lithium: Another therapeutic myth? The Lancet 291(7549): 968-971. 19. Baastrup PC, Poulsen JC, Schou M, Thomsen K, and Amdisen A (1970) Prophylactic lithium: double blind discontinuation in manic-depressive and recurrent-depressive disorders. The Lancet 296(7668): 326-330. 20. Lehmann HE and Kline NS (1983) Clinical discoveries with antidepressant drugs, in: Discoveries in Pharmacology: Psycho- and Neuro-pharmacology (Parnham MJ and Bruinvels J eds.) pp. 209-221, Elsevier, New York. 21. Ponte K (September 23, 2021) Bipolar depression: The lows we don’t talk about enough. NAMI; available from: https://www.nami.org/Blogs/NAMI-Blog/ September-2021/Bipolar-Depression-The-Lows-We-Don-t-Talk-About-Enough. 22. Smith KA and Cipriani A (2017) Lithium and suicide in mood disorders: updated meta-review of the scientific literature. Bipolar Disord 19(7): 575-586.

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 feature American biochemist, pharmacologist and Nobel Prize recipient Gertrude Elion

Don't miss the September 2022 issue.

The Pharmacologist • June 2022

Education News Highlights of the Association of American Medical Colleges Council of Faculty and Academic Societies (AAMC-CFAS) Annual Meeting Marieke Kruidering (University of California-San Francisco) and Joe Blumer (Medical University of South Carolina) as junior and senior faculty society representatives, respectively, represented ASPET at the 2022 Association of American Medical Colleges Council of Faculty and Academic Societies (AAMCCFAS) annual meeting. ASPET participates as an AAMC-CFAS member society. CFAS provides a platform for faculty at academic medical centers to identify critical issues facing medical school faculty and academic societies and provide a voice for faculty in the creation and implementation of AAMC programs. A total of 130 AAMC-CFAS representatives attended the 2022 annual meeting, held virtually on April 11–13. The AAMC-CFAS featured topics including the relationship between faculty and institutional leadership, shared governance structures, leadership development, faculty wellbeing, professional identity for faculty, and the influence of diversity, equity and inclusion on the faculty experience. Several sessions centered around the intersection and interaction between leadership of academic medical centers (e.g., CEOs, presidents, chancellors) and faculty. The first session highlighted the intrinsic value of academic medicine, in particular research, discovery, and education, to non-medical leadership who may be more focused on fiscal concerns. Examples of such intrinsic value include innovation and discovery, lower mortality rates for patients admitted to teaching hospitals at academic medical centers compared to non-teaching hospitals and the energy of students and trainees that helps foster stimulating research and

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learning environment. Participants indicated that many institutions do not appear to be sufficiently valuing faculty contributions to their missions; this was felt particularly among basic science faculty who perceive more value being placed on the clinical enterprise rather than research and education. The attendees also expressed concerns about the merging of basic science departments and the increasing number of non-tenure track faculty who feel they have very little voice, whose employment can be easily terminated, and who feel viewed as second-class citizens in academic medical centers. In response, the AAMC-CFAS Mission Alignment Committee advocates for a strong faculty voice to ensure that governance structures ultimately serve core departmental missions. Given the many governance models that exist, CFAS is exploring pros and cons of the various models to help identify what a healthy governance structure looks like so that faculty can feel supported. Sessions on the second day focused on leadership, including the journey from faculty to institutional leadership, drawing from personal experiences from the invited speakers. Leadership development was emphasized as part of the new 10-part AAMC strategic plan (see https://www.aamc.org/what-we-do/ strategic-plan/healthier-future-all-aamc-strategicplan#actionplans), in which Plan #6 seeks to enhance the skills and capacity of people in academic medicine. AAMC’s leadership development initiative will allow member institutions to grow and diversify their leadership pipelines with increased access through new delivery models. Models include offering

Leadership Development Flagship Programs with open enrollment that do not require a leadership appointment to allow a focus on core leadership skills and Foundational Programs for trainees and students to learn foundational leadership skills. Leadership Development Enrichment Programs, some of which are currently available, are more targeted for a specific role or demographic, e.g., leadership programs for early career women. ASPET will provide updates to members as to when these Leadership Development Programs are available for enrollment. Efforts to improve diversity, equity, and inclusion (DEI) in medicine were discussed in a presentation by Malika Fair, MD, MPH, FACEP, who shared Plan #3 of the AAMC strategic plan, “Equipping Academic Medicine to be more Inclusive & Equitable.” She shared the work that has been done thus far regarding DEI competencies https://tinyurl.com/4xawazrt and stated that advancing equity, diversity and inclusion in academic medicine will require intentional engagement of all individuals and leaders in our nation’s medical schools and teaching hospitals. The goal of Action Plan 3 is to equip institutions and leaders at every level with data, tools, training, and evidence-based best practices. Action Plan 3 has seven areas of focus including: 1. Gender Equity 2. Anti-Racism 3. Climate & Culture Assessment Tools 4. Leadership Development 5. DEI Research 6. RJAM (Restorative Justice in Academic Medicine). This involves facilitator training that provides guidance to effectively incorporate the practice of restorative justice for advancing DEI in academic medicine. Participants gain the tools to address the impact of harms, deter recidivism, and facilitate collaborative solutions within medical schools, teaching hospitals, and allied health professional institutions. 7. Ideas, e.g., a monthly webinar series that brings in experts from across academic medicine to

help foster inclusive environments, create equitable advancement, promotion, and tenure policies, and promote anti-racist policies, education, and institutional practices. www.aamc.org/ideas For more information on Action Plan #3, visit www. aamc.org/diversity. The 8 CFAS subcommittees updated participants about the Advocacy Committee actions to help coordinate a sign-on opportunity for the AAMCconvened Ad Hoc Group for Medical Research’s recommendation of at least $49 billion for the NIH’s base budget and for additional funding for other targeted programs like pandemic preparedness; it should be noted that ASPET is one of the sign-on societies. The Biomedical Research and Education Committee announced efforts to explore the impacts of regulatory burden on research and discovery efforts of faculty. ASPET will continue to engage with CFAS to ensure the AAMC and the public hears ASPET members’ voice and concerns as pharmacologists. As representatives to CFAS, ASPET is keen to advocate for the concerns of members at CFAS meetings. Please email ASPET with issues you would like raised at the next CFAS meeting. Visit the CFAS website for more information and resources: https://www.aamc.org/members/cfas/. Joe Blumer, PhD Department of Cell and Molecular Pharmacology and Experimental Therapeutics Medical University of South Carolina Charleston, SC blumerjb@musc.edu Marieke Kruidering-Hall, PhD Department of Cellular and Molecular Pharmacology University of California San Francisco San Francisco, CA marieke.kruidering@ucsf.edu

The Pharmacologist • June 2022

ASPET Names 2022 Individual Summer Undergraduate Research Fellows ASPET congratulates three students who have been named 2022 individual Summer Undergraduate Research Fellows (SURF). The individual fellowships support students whose home campus lacks an institutional program, or who seek more specialized training opportunities at a different university. Each student participating in the SURF program will be introduced to pharmacology Alexandra Dunstan Madeline Elsey Alyson (Xiaolei) Meng research through a 10-week summer laboratory research experience. State University College of Pharmacy. Her summer Alexandra Dunstan will be working with Dr. Amreen research will focus on how dysfunction of a specific Mughal to evaluate vascular pathophysiology of pool of sodium channels contributes to impaired Alzheimer’s disease (AD). Alex will conduct vascular electrical impulse propagation in the diabetic heart function assessments using pial vessels from the mouse through immunolabeling, optical mapping, and brain to identify possible vascular pathology in AD. electrocardiography. Madeline Elsey will be working in the Behavioral ASPET offers both institutional and individual Pharmacology Laboratory under the mentorship of SURF awards. The program uses authentic, mentored Dr. Katherine Serafine at The University of Texas at El research experiences in pharmacology to heighten Paso, where she will investigate the impact of eating a student interest in careers in research and related high fat diet on the therapeutic effects of morphine. health care disciplines. Institutions with funded Alyson (Xiaolei) Meng will be working in the fellowship programs are listed at: http://www.aspet. laboratory of Dr. Przemyslaw Radwanski at the Ohio org/awards/SURF/institutional-Funded/.

Programs like the Summer Undergraduate Research Fellows are not possible without continued financial support. Funds are used solely to provide stipends and housing during the summer research period. To donate, please visit https://www.aspect.org/donate/

The Pharmacologist • June 2022

Science Policy News ASPET Joins Organizations Supporting Funding Growth for NIH ASPET is one of about 400 members of the Ad Hoc Group for Medical Research, which includes organizations representing patients, scientists, health professionals, research and academic institutions, educators, and industry. The Ad Hoc Group commends Congress for making the annual funding growth for the National Institutes of Health (NIH) a national priority. NIHfunded biomedical, behavioral, social, and populationbased research improves our understanding of fundamental life and health sciences, equips the nation to combat both known and unprecedented health threats and converts the hope of improved health into a reality for patients and their families. The Ad Hoc Group points out that the federal investment in this lifesaving work in labs across the country also has a multiplier effect in local and regional economies. The work catalyzes new industries, enhances the United States’ global competitiveness, establishes viable career paths for aspiring scientists of diverse backgrounds and generates other high-quality jobs across the country.

To promote the sustained, robust growth necessary to make consequential progress against pressing health challenges in fiscal year (FY) 2023, the Ad Hoc Group recommends an increase in funding for programs. The group is requesting at least $49.048 billion (about $150 per person in the U.S.) for the NIH base budget, representing an increase of $4.1 billion over the comparable FY 2022 funding level (an increase of $3.5 billion or 7.9% in the NIH appropriation plus funding from the 21st Century Cures Act for specific initiatives). In addition, the group strongly urges lawmakers to ensure that any funding for the new Advanced Research Projects Agency for Health (ARPA-H) supplements the group’s $49 billion recommendation for NIH’s base budget, rather than supplants the essential foundational investment in the NIH. Further, the coalition supports the president’s proposal to supplement NIH’s budget with additional mandatory funding to propel the pace of pandemic response and readiness.

ASPET Joins WHAM-backed Resolutions to Expand Women’s Health Research Along with more than 25 other leading health organizations, ASPET joins Women’s Health Access Matters (WHAM) in calling for Congress to accelerate women’s health research. Because women are more than 50 percent of the U.S. population, diseases that disproportionately affect women should be at the forefront. The medical research gender gap is not only a detriment to women’s health, but it is also holding back the American economy.

Senator Tammy Duckworth and Representative Jan Schakowsky recently introduced a resolution highlighting new data from The WHAM Report that shows clear disparities in funding and builds the economic case for change, showing that small investments have outsized economic returns. Adding $300 million for research focused on women across just three disease areas will bring back $13 billion to our economy. ASPET is proud to support this effort to drive change.

The Pharmacologist • June 2022

ASPET and the Friends of the VA Call for $980M for Medical and Prosthetic Research ASPET has joined about 100 organizations requesting an 11 percent increase, or a total of $980 million, to fund many important programs through a spending bill supporting America’s veterans. The Friends of the VA (FOVA) is urging Congress to continue its continual growth in the VA research program without recissions. FOVA’s FY 2023 budget recommendation for the VA ensures meaningful growth above inflation to address long-term health impacts of COVID-19, health disparities, and increase clinical trials access. At the same time, the additional funding will help renew support for groundbreaking programs like the Million Veteran Program (MVP), VA’s participation in the Cancer Moonshot Initiative, and research on chronic and emerging needs of the nation’s veterans. Increased funding for the VA research program will also support researchers as they recover from

slowed research progress during the pandemic and allow for additional investments to support the strained IT capacity through computational science purchases to enhance the collection and use of big data. Sustained and predictable funding growth for VA research is imperative to help ensure the best return on investment in improving the health of veterans and all Americans. FOVA recommends the funding to invest in physical and IT research infrastructure that is needed to support research with state-of-the-art facilities, technology and equipment that have not been upgraded for decades. For FY 2023, more than $200 million was estimated to correct all deficiencies; however, FOVA is seeking at least $100 million to address the most pressing problems.

ASPET Supports NIH’s DEIA Agency-wide Strategic Plan Framework ASPET offered several suggestions in comments to the National Institutes of Health (NIH) in response to its Request for Information on its framework for an agency-wide strategic plan to address diversity, equity, inclusion and accessibility (DEIA). ASPET is committed to identifying and dismantling barriers to the full participation of its membership in the biomedical sciences workforce. The overall goal is to create more opportunities for marginalized populations to train at NIH and then to provide an inclusive environment for them to thrive and develop as leaders and scientists. Opportunities would include increasing the diversity of advisory panels, webinars, symposia and training sessions. Another area where DEIA principles are needed is in the enrollment of patients for clinical trials. Consideration and inclusion of diverse genetic, ethnic, metabolomic, and proteomic backgrounds is important to best understand what constitutes a healthy state for an individual and for investigating the safety and effectiveness of interventions in a population.

The Pharmacologist • June 2022

As part of its DEIA strategic plan, ASPET encourages NIH to explore the interrelation more fully between culture and medicine. The use of natural products to cure ailments and diseases is well-documented, and modern methods of drug discovery that isolate active compounds owes a great debt to this cultural knowledge. But the use of natural products in drug discovery poses many challenges (e.g., diversification of possible therapeutic lead compounds by the derivatization of a promising isolated natural product compound), and their use by large pharmaceutical companies has been declining for decades. This decline is occurring despite the screening of only a fraction of the planet’s biodiversity for biological activity. Natural products can help us understand human health and development of therapeutics and learn from other cultures to guide us in our search for new ways to fight disease. Visit https://www.aspet.org/aspet/advocacy to learn more.

2022 Washington Fellows The 2022 Washington Fellows were recognized at the 2022 ASPET Annual Meeting at Experimental Biology in Philadelphia. They participated in a virtual advocacy training in preparation for virtual Capitol Hill meetings with their congressional representatives and staff. Following their day on Capitol Hill, the Fellows gathered for an in-person awards dinner at the start of the annual meeting.

The Washington Fellows program is designed to prepare early career scientists interested in science policy to learn and become more engaged in public policy issues. For more information, visit https://www.aspet.org/aspet/advocacy/aspet-washington-fellows-program.

The ASPET Fellows Nominations are Open Deadline is July 22, 2022

St. Louis Union Station Hotel May 18–21 WHEREVER YOU ARE FROM, COME HOME TO ASPET! Arrive in St. Louis, feel the warmth and sense the PRIDE of ASPET members. Take in the attractions and SOCIALIZE with your colleagues. PARTICIPATE in learning sessions that display excellence in science, and promote cross-disciplinary and translational research. Engage and ENJOY in the sharing, mentoring and awe of the accomplishments of ASPET members. CELEBRATE with people you care about and discuss topics across the field of pharmacology.

MEET US IN ST. LOUIS, WHERE YOU BELONG! The Pharmacologist • June 2022

TOP FIVE

PLACES TO VISIT IN AND AROUND ST. LOUIS UNION STATION HOTEL

Gateway Arch

Missouri Botanical Garden

St. Louis Wheel

St. Louis Aquarium

St. Louis Carousel

The Pharmacologist • June 2022

Journals News Call for Papers – Emerging Roles of Lipids in Membrane Protein Function A special section on the many active roles of membrane lipids in the structure, function, and ligand recognition of integral membrane proteins such as GPCRs and ion channels is planned for publication in the February 2023 issue of Molecular Pharmacology. Submissions will be taken through the end of June 2022. The roles of cell membranes in the proper localization, structure, and function of integral membrane proteins are well established. However, a growing body of evidence suggests that membrane lipids play more sophisticated roles in protein function. For example, lipids may directly or indirectly act as allosteric modulators of signaling receptors and ion channels to regulate their function. Further, the

diversity in the lipid composition and biophysical properties of membranes in different organelles by determining conformational dynamics of receptors can drive spatial bias in signaling and functional outcomes. This special issue will broadly cover original research and review articles on how membrane lipids regulate integral membrane proteins. Review articles addressing any aspects of the structural and functional roles of membrane lipids will also be considered. Proposals for such articles should be sent to the guest editors, Senthil Natesan (senthil.natesan@wsu.edu) and Manoj Puthenveedu (puthenve@umich.edu), for approval before submission.

DMD Special Section of Bile Acids, Drug Metabolism, and Toxicity This Drug Metabolism and Disposition Special Section of “Bile acids, drug metabolism, and toxicity” includes five featured review articles and one research article that focuses on bile acids, drug metabolism, and toxicity. The review articles cover molecular mechanisms in regulation of bile acid homeostasis; environmental chemical contribution to the modulation of bile acid homeostasis through FXR signaling; the role of PXR in gut-liver interactions on drug metabolism and toxicity; a novel approach for

The Pharmacologist • June 2022

diagnosing nonalcoholic steatohepatitis by applying advanced pharmacokinetic biomarkers; the role of Nrf2 in allergy and asthma; and the mechanisms for alterations of drug metabolism by thyroid hormones. The research article highlights effects on drug metabolism by overexpression of FGF15/19. All articles in the special section found in Drug Metabolism and Disposition April 2022 (50/4) issue are freely accessible through October 31, 2022.

Pharmacology Research & Perspectives Introduces: Pharmacology Education and Innovation Series PR&P has launched a series with the title “Pharmacology Education and Innovation.” Articles published so far as part of this series can be found here: https://bpspubs.onlinelibrary.wiley.com/ doi/toc/10.1002/(ISSN)2052-1707.pharm-ed Pharmacology education is an essential element of biomedical science and practice. Knowledge of drug action on biological systems, patient outcomes, and how the body responds to pharmacological interventions are key curricular competencies in schools of medicine, nursing, pharmacy, dentistry, physiotherapy, and veterinary medicine, particularly in the context of disease and variable physiological and clinical parameters. In addition, emerging biomedical scientific developments require the continual evolution of pharmacology educational methodology and practices. Assessing the downstream utility and practice of such training in the research and clinical settings, by way of clinical efficacy, toxicity, and adverse prescribing behaviors provides valuable opportunities to evaluate the quality of educational outcomes in pharmacology.

Call for Papers – Now Open Educational research-related papers have been a key component of the content published in PR&P in recent years. To build on this important feature of the journal and to further the advancement of pharmacology education, PR&P has opened a call for papers on all aspects of current and future

pharmacology education including: ■ Curriculum development ■ Learning strategies ■ New pedagogical models ■ Approaches to the delivery of pharmacology content More information about this call for papers can be found on the call for papers page (found at https:// bpspubs.onlinelibrary.wiley.com/hub/journal/20521707/ cfp_pharmacology_education) and in the Editorial (found at https://bpspubs.onlinelibrary.wiley.com/doi/ full/10.1002/prp2.772) by the Editor-in-Chief, Dr. Mike Jarvis, and Deputy Editor, Dr. Jennifer Martin.

Submission Requirements As part of this series, submissions of all article types (e.g., Original Articles, Reviews, Commentaries) are encouraged. The PR&P Author Guidelines provide further information about submission requirements for manuscripts submitted as part of the series, and can be reviewed here: https://bpspubs.onlinelibrary.wiley. com/hub/journal/20521707/author-guidelines.html

APC Discount Articles accepted as part of the Pharmacology Education and Innovation Series are also eligible for a 20% discount on the Article Publication Charge, the details of which can be reviewed at: https://bpspubs. onlinelibrary.wiley.com/hub/journal/20521707/articlepublication-charges.html.

The Pharmacologist • June 2022

Highlighted Trainee Authors Congratulations to the latest Highlighted Trainee Authors selected for Drug Metabolism and Disposition, The Journal of Pharmacology and Experimental Therapeutics, and Molecular Pharmacology:

Drug Metabolism and Disposition ■ Deepak Ahire (Washington State Univ.) – March ■ Joe Lim (Univ. of Washington) – April ■ Yifan Bao (Univ. of Connecticut) – May

Deepak Ahire

Joe Lim

Shawn M. Flynn

Sarah Elmer

Fereshteh Ahmadinejad

Christian Egly

Yifan Bao

JPET ■ Shawn M. Flynn (Univ. of Texas Health Sci. Ctr. at San Antonio) – March ■ Sarah Elmer (Texas A&M Coll. of Medicine) – May

Molecular Pharmacology ■ Fereshteh Ahmadinejad (Virginia Commonwealth Univ.) – March ■ Christian Egly (Purdue Univ.) – April ■ Shalini Dogra (Vanderbilt Univ.) – May Shalini Dogra

A brief description of their areas of research, current projects, the anticipated impact of their work, and what they enjoy when not in the lab is online at https://bit.ly/2yX1YeH. We congratulate all of them for being selected.

The Pharmacologist • June 2022

Membership News ASPET 25 Year Members ASPET thanks the following members who have devoted 25 years of service to ASPET and their commitment to the growth of our discipline. Nathan M. Appel, PhD William T. Beck, PhD Michael P. Blanton, PhD John N. Buchholz, PhD Lisa A. Cassis, PhD Thomas K. Chang, PhD Olivier Civelli, PhD Susan P. Cole, PhD Nissar A. Darmani, PhD Daryl L. Davies, PhD Martha I. Davila-Garcia, PhD Xinxin Ding, PhD Stephen W. Edwards, PhD Ayman O. El-Kadi, PhD Tim A. Esbenshade, PhD Javier Garzon, PhD Joel M. Goodman, PhD

Julie G. Hensler, PhD Yoshiaki Hikasa, PhD Herbert Himmel, MD Keren I. Hulkower, PhD Peter C. Isakson, PhD Linda G. Jones, PhD Irwin Lucki, PhD David R. Luthin, PhD David J. Mangelsdorf, PhD John D. Minna, MD Sidney S. Negus, PhD Stephen T. O’Rourke, PhD Ebenezer T. Oriaku, PhD Tom J. Parry, PhD Margaret A. Phillips, PhD Arthur V. Prancan, PhD John D. Scott, PhD

Dana E. Selley, PhD Laura Sim-Selley, PhD Quentin R. Smith, PhD Alan V. Smrcka, PhD Douglas K. Spracklin, PhD Kelly M. Standifer, PhD Yuichi Sugiyama, PhD Michael D. Swedberg, PhD Stephen F. Traynelis, PhD John R. Traynor, PhD Xinkang Wang, PhD James H. Wible, Jr, PhD Paula A. Witt-Enderby, PhD Yung H. Wong, PhD John D. York, PhD

ASPET 50 Year Members ASPET thanks the following members who have devoted 50 years of service to ASPET and their commitment to the growth of our discipline. Khalil Ahmed, PhD Desiree A. Armstrong, PhD Jack D. Barchas, MD William Stephen S. Brimijoin, PhD Gerald W. Camiener, PhD David E. Clarke, PhD Frank N. Dost, DVM Cristobal G. Duarte, MD Donald C. Dyer, PhD Carlton K. Erickson, PhD Morris D. Faiman, PhD Ralph I. Freudenthal, PhD Duane G. Gallo, PhD James E. Gibson, PhD

Thomas M. Glenn, PhD Stanley D. Glick, MD, PhD Irving H. Goldberg, MD, PhD Joseph P. Hanig, PhD Israel Hanin, PhD Enrique Hong, DSc Susan Band Horwitz, PhD Garland A. Johnson, PhD Harvey R. Kaplan, PhD Gopal A. Krishna, PhD Atul R. Laddu, MD, PhD Yien-Hwei Lee, MD, PhD Ole J. Lorenzetti, PhD Myron A. Mehlman, PhD

Thomas W. Mittag, PhD Alan S. Nies, MD Domenico C. Regoli, MD, PhD D. V. Sankar, PhD John H. Sanner, PhD Nguyen B. Thoa, PhD David J. Triggle, PhD Richard M. Weinshilboum, MD James H. Woods, PhD Raymond L. Woosley, Jr, MD, PhD

The Pharmacologist • June 2022

New Members Postdoctoral Members Pouria Fattahi, Univ of Pennsylvania Churchill J. Ihentuge, Univ of Pikeville, KY Monica R. Langley, Mayo Clinic, MN Antonio G. Soares, UT Health Science Center at Houston, TX Shang Su, The Univ of Toledo, OH Wenli Yang, The Univ of Texas Health Science Center at Houston

Regular Members Hosam G. Abdelhady, College of Osteopathic Medicine Sam Houston Univ, TX Farzana Alam, Texas Tech Univ Health Sciences Center El Paso Jacqueline Barker, Drexel Univ College of Medicine, PA Arti Bhujade, NJ Biopharmaceuticals LLC, NJ Jeremy W. Chambers, Florida International Univ Abhijit Date, Univ of Arizona Narsimhaswamy Dubasi, Belcher Pharmaceuticals LLC, FL Douglas C. Eaton, Emory University Medical School, GA Amber Frick, Univ of North Carolina Eshelman School of Pharmacy Peter J. Gaskill, Drexel Univ College of Medicine, PA Kristine Griffett, Auburn Univ, AL Saadet Inan, Lewis Katz School of Medicine at Temple Univ, PA Sani M. Ismaila, The Univ of the West Indies, Trinidad And Tobago Roger A. Laine, Louisiana State Univ Josh Lott, miLEAD Consulting, MI Subhi Marwari, Univ of Pennsylvania, PA Bryan McCranor, US Army Medical Research Institute of Chemical Defense, William D. McGuinn, Jr, Drug Development Services, IN Brooks McPhail, Univ of South Carolina School of Medicine Greenville Shona A. Mookerjee, Touro Univ California Andreia C. Mortensen, Drexel Univ College of Medicine, PA Khawla Nuseir, Jordan Univ of Sci & Tech= Emmanuel U. Onyekwelu, Legacy Univ & Classics/ Revits in Sci Med, Gambia Mayur S. Parmar, Nova Southeastern Univ, FL Kelsey Retting, Crinetics, CA Cai M. Roberts, Midwestern Univ, IL

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Vinay K. Sharma, NICHD, NIH, MD Bing Yang, The Univ of Tennessee Health Science Center Ling Yang, Shanghai Univ of Traditional Chinese Medicin, China Yara Zayed, St. Michael’s Hospital, Canada Huiliang Zhang, Univ of Arkansas for Medical Sciences

Graduate Student Members Sifat M. Alam, Univ of California San Diego Ashline Paul Manoucheca Amilcar, Instituto Nacional de Cardiología, Mexico Christina Besada, Drexel College of Medicine, PA Joanna A. Canagarajah, Drexel Univ, PA Breana Channer, Drexel Univ, NJ Matt Coban, Mayo Clinic, FL Laura Danner, Medical Coll of Wisconsin Paramita Gayen, Indian Inst of Sci Educ and Res Kolkata Simran Gill, Drexel Univ College of Medicine, PA Gregory J. Grumbar, NIH/NIMH, MD Laura Huerta Sanchez, Univ of California Santa Barbara Jennings Luu, Case Western Reserve Univ, CA Peter Nwokoye, University of Cambridge, United Kingdom Emmanuel O. Okwuofu, III, Univ Putra Malaysia Nicholas Oldberg, Univ of California, Davis Katelyn L. Reeb, Drexel University College of Medicine, PA Daihyun Song, Univ of Minnesota Yearam Tak, St. Louis College of Pharmacy, MO Aruvi Vijikumar, West Virginia Univ

Undergraduate Student Members Alexdiel Figueroa, Univ of Puerto Rico, Rio Piedras Megan E. Kohout, College of Saint Benedict, MN Md. Rasel Mahmud, University, Bangladesh Keelin Norman-Klatt, Beloit College, WI Caitlyn Nuehring, Univ of Northern Iowa Diandra Panasis, Rowan Univ, NJ Tanvikhaa Saravanan, Univ of Texas at Tyler, TX Hyogun Yi, Rutgers State Univ, NJ

Post-baccalaureate Student Members Aanu Ayeni, Oregon Health and Science Univ Rebecca Schelling, NIH, MD

In Memoriam ASPET notes with sympathy the passing of the following members: Sue Piper Duckles, PhD, FASPET Marc G. Caron, PhD, FASPET

In Memoriam: Sue Piper Duckles, PhD, FASPET, 1946-2022 Submitted by Diana Krause, PhD On January 24, 2022, Sue Piper Duckles passed away and we lost a distinguished and well-loved member of ASPET (1979-2022). Sue was an exceptional leader, an outstanding researcher, an invaluable collaborator, a sage mentor, an inspiring role model and a dear friend and colleague. She was a world-renown pharmacologist and a tireless advocate for advancing the discipline of pharmacology and the careers of pharmacology students and professionals. A native Californian, Sue Piper Duckles grew up in the hills of Oakland which instilled in her a lifelong love of nature, hiking, camping, and native plant restoration. She obtained her B.A., cum laude, in Philosophy from UC Berkeley in 1968. At that time, she married Lawrence Duckles, a professional flutist, and also made the fateful decision to pursue a Ph.D. in Pharmacology & Toxicology at UC San Francisco. In 1973, Dr. Duckles moved to UCLA as an NIH Postdoctoral Fellow and then Assistant Professor in the Department of Pharmacology. From 1979 -1985, she was a pharmacology faculty member at the University of Arizona College of Medicine, Tucson, in the department of Dr. Thomas Burks, a key mentor in her career. In 1985, Sue was recruited to the Department of Pharmacology in the School of Medicine at UC Irvine, where she remained until her retirement as Professor Emerita in 2010. In 2019, Sue Duckles was named to the inaugural class of ASPET Fellows for her overall impact on pharmacology and the Society. She provided

outstanding leadership and guidance to ASPET, serving as President (19971998), Councilor (1992-1995) and on numerous committees. In recognition of her achievements, Sue was presented the ASPET Torald Sollmann Award in Pharmacology (2007) and the Paul M. Vanhoutte Award in Vascular Pharmacology (2014). Sue also received the PhRMA Foundation Award in Excellence in Pharmacology/Toxicology (2007) and was named an honorary fellow of the British Pharmacological Society (2005). A gifted administrator and organizer, Sue Duckles also served as President (2006-2010), Secretary General (2002-2006) and General Assembly Delegate of the International Union of Pharmacology (IUPHAR). In addition, she was President of the Western Pharmacology Society (1992) and a member of the Board of Directors and Vice President for Science Policy for the Federation of American Societies for Experimental Biology (1997-2001). During her career, she helped organize numerous meetings and symposia; most notably, she was Congress President for the XIVth World Congress of Pharmacology held in San Francisco (2002). In addition, Sue provided strong leadership within her own institution, serving as Chair of the UCI Academic Senate (1990-1992), Interim Chair of the UCI Department of Pharmacology (2000-2005) and Associate Dean for Faculty Affairs and Development in the UCI School of Medicine (1993-2010). As a cerebrovascular pharmacologist, Sue Duckles was world renown for her pioneering research on

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the influence of sex hormones on the vasculature. Together with her long-time collaborator, Diana Krause, Sue discovered that estrogen acts directly on receptors in brain blood vessels to influence a variety of cellular and contractile responses. Groundbreaking studies by her research team established that estrogen protects vascular mitochondria by increasing mitochondrial efficiency and suppressing free radicals. Her studies elucidated mechanisms that underlie sex differences and hormonal influences in vascular function and age-related diseases such as stroke. In 1996, she helped organize a seminal ASPETsponsored colloquium, “Effects of gonadal steroids on vascular function” that brought hormone experts together with vascular biologists for the first time. For over 20 years, Sue contributed to and promoted the importance of the study of sex and hormonal influences in cardiovascular research. When Sue joined ASPET in 1979, only about 10% of the members were women. To become a successful woman in science, Sue often had to break gender barriers and persevere with few role models and little mentorship. Sue constantly moved forward with confidence, smarts, a warm smile and laser focus on her goals. She was an excellent communicator, gifted writer

and a natural leader who embraced collaboration. She was always firm, fair, respectful and kind. Throughout her life and career, Sue Duckles had a profound influence on others. She was a powerful role model, especially for women in science. Sue was an outstanding advisor and example – of how to think critically and do good science, how to advance your career, and how to maintain balance and enjoy life. She modeled how to prioritize her interests and passions, which included her role as wife and mother. Sue used her position and experience to guide and support junior scientists and faculty members. A pioneer in promoting diversity and inclusion, she was an encouraging and supportive mentor for all. Maybe because she started off studying philosophy, Sue had a unique perspective on a career in science. When asked to give a retrospective lecture on her journey, Sue titled it “A career in pharmacology: In search of beauty and joy”. Sue Duckles is survived by her husband of 54 years, Lawrence Duckles, and her sons Ian (wife Heather) and Galen. She will be greatly missed and fondly remembered by her many students, mentees, co-workers and colleagues.

In Memoriam: Marc Caron, PhD, FASPET 1946-2022 Submitted by Laura M. Bohn, PhD “Let’s read it out loud with feeling” is how Professor Marc Caron would begin a paper writing session. Every word read out loud, pausing to rewrite for clarity and flow, each paper receiving his attention and care. And indeed, there were many publications, all written with the desire to engage the reader and to share the science that Marc loved so much. Professor Marc Caron, passed away on April 25, 2022. Dr. Caron held the title of a James B. Duke Distinguished Professor of Cell Biology at Duke University, where he also served as the Vice-Chair for Science and Research in the department. He received his PhD in 1973 from the University of Miami and had made Duke his academic home since 1977.

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Dr. Caron’s scientific accomplishments were wide in scope and impactful. He approached science with a desire to not only delineate mechanisms, but to understand the physiological impact of molecular-level findings. Marc published over 650 manuscripts and was awarded the Julius Axelrod Award in Pharmacology (2005) as well as the Goodman and Gilman Award in Receptor Pharmacology (2018) from the American Society of Pharmacology and Experimental Therapeutics (ASPET). He was a Howard Hughes Medical Institute Investigator for over a decade, a member of the American Academy of Arts & Sciences, and a fellow of the American Association for the Advancement of Science.

Many knew Marc for his seminal work on G protein couple receptor (GPCR) pharmacology; his early contributions include pioneering work cloning GPCRs and regulatory proteins and demonstrating their function in cellular models. Marc was the first to clone the D1 and D5 dopamine receptors and was the first to show that the dopamine D2 receptor signals through arrestins. Moreover, he was the first to show that morphine differentially regulated mu opioid receptor trafficking compared to enkephalins, laying the foundation for examining biased opioid receptor signaling. In more recent years, Marc identified new drug candidates for the neurotensin 2A receptor. Dr. Caron was known for extending his biochemical findings into biologically relevant neurological systems. In addition to his work on GPCRs, Marc made seminal contributions to understanding neurotransmitter homeostasis. He famously described the hyperactivity of the dopamine transporter knock out (DAT-KO) mouse. This important model, along with others mouse models described in the laboratory, has served as an important model for studying Parkinson’s Disease, Huntington Disease, schizophrenia and attention deficit hyperactivity disorder. Indeed, Marc embraced new technological approaches and employed genetic models to understand the impact of molecular interactions on physiological responses;

he was also known to be generous in sharing many of these models. In addition to his highly productive research career, Marc was a true academic, serving his university and the scientific community in many ways: as a Center of Scientific Review study section member; course director; faculty mentor and recruiter; graduate student mentor and teacher. In 2018, he was honored for his mentorship, receiving the Research Mentoring Award for Basic Science at Duke. Dr. Caron was an editor for the Journal of Clinical Investigation and served as the editor for Biochemistry. Marc welcomed scientists from around the world to his laboratory and had an extensive network of collaborators. He was a welcomed addition to scientific programs as he was an excellent speaker, his passion and excitement for his research were readily shared. Family was always very important to Marc and those of us who had the fortune to spend time in his lab, either as a trainee or a visiting scientist, can attest to that. He launched the careers of so many of us and we are grateful for his mentorship. Marc pushed us to be our best and to work hard, setting a strong example by his own dedication to research. Each Friday evening, he would leave the lab to say: “Have a good weekend, see you tomorrow…” We will miss you, Marc.

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Chapter News Great Lakes Chapter Holds Annual Regional Meeting Submitted by Takeshi Shimamura, PhD Nearly 100 attendees from the greater Chicago area, Michigan and Arizona attended ASPET’s Great Lakes Chapter’s (GLC) annual meeting held recently. The inperson meeting took place at Lake Forest College, Lake Forest, Ill. in June. Centered around this year’s theme “Metabolism: Emerging Target in Human Disease,” Dr. Navdeep S. Chandel, PhD, of the Northwestern University served as the keynote speaker. The 2022 meeting highlighted recent advances in the roles of cellular metabolism in human diseases and pharmacological advances targeting metabolism to overcome the diseases. The GLC meeting has historically provided an opportunity for learning and exchanging ideas in all fields of pharmacological sciences. It has also served as a major networking event for biomedical scientists in the Great Lakes region of the Midwest. The annual meeting included 32 poster presentations covering a range of pharmacological topics including pharmacokinetics, drug resistance, investigation of cancer drug targets, marine pharmacology, cannabinoid pharmacology, neuropharmacology including oxytocin, Parkinson’s, and Alzheimer’s research; stress response; regulation of metabolism by immune system, nanotechnology, development of new assays for drug response studies, non-endocrine pharmacology, immunopharmacology and impact on metabolism, medicinal chemistry, pharmacology educational research.

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Poster presentations were judged in graduate and undergraduate categories with up to five awards presented per category. Poster prizes for the best posters were presented to the following: ■ Postdoctoral Level • 1st: Ines Pulido, PhD (University of Illinois Chicago) ■ Graduate Level • 1st: Emily Zaniker (Northwestern University) • 2nd: Sujin Seo (Midwestern University) • 3rd: Qiyue Luan (University of Illinois Chicago) • 4th: Marissa Gehr (Midwestern University) ■ Undergraduate level • 1st: Biau H. Grimes & Ceylin K. Sahin (Lake Forest College) • 2nd: Laurel K. Robbins (Lake Forest College) • 3rd: Kamden T. Kuklinski (Lake Forest College) • 4th: Amanda Grassel (Lake Forest College) • 5th: Maria Jose Orozco Fuentes (Lake Forest College) Scientists, graduate students and undergraduate students attended the one-day event. The chapter also acknowledged councilors who have served in the GLC-ASPET Executive Committee and recognized those who have been elected for the next term. Service awards were presented to Ricardo Monzon, PhD, Saint Xavier University, who served as Treasurer and Rebecca Kohnken, D.V.M., PhD, DACVP, who served as a Councilor.

The following positions in the GLC-ASPET Executive Committee were approved. ■ GLC ASPET Treasurer, 2022-2025 • Adriana Caballero, PhD, University of Illinois Chicago ■ GLC ASPET Secretary, 2022-2025 • William Conrad, PhD, Lake Forest College ■ GLC ASPET Councilors, 2022-2024 • Yevgeniya E. Koshman, PhD, AbbVie, Inc. • Joanna Dabrowska, PhD, PharmD., Rosalind Franklin University of Medicine and Science The 36th GLC-ASPET annual meeting will be held at University of Illinois Chicago. Further details will be forthcoming.

Currently, ASPET’s three regional chapters offer students and postdoctoral fellows opportunities to attend regional meetings to share and discuss their research through poster sessions. Regional chapters are ASPET-affiliated but operate separately from ASPET. Regional chapter members may or may not be members of ASPET. Visit https://www.aspet.org/aspet/membershipcommunity/aspet-regional-chapters/great-lakeschapter to learn more about the Great Lakes Chapter or contact Chapter President Takeshi Shimamura, PhD at tshima2@uic.edu.

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Division News DPE Inducts Three New Fellows into the Academy of Pharmacology Educators The Division for Pharmacology Education (DPE) inducted three new fellows into The Academy of Pharmacology Education this year. The Academy of Pharmacology Educators was established in 2010 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. Additional information about the Academy, including application instructions and a roster of inductees, can be found here: https://bit.ly/38T6nCI Dr. Joe B. Blumer is an Associate Professor in the Department of Cell and Molecular Pharmacology and Experimental Therapeutics at the Medical University of South Carolina (MUSC) College of Medicine. He received his PhD in microbiology and molecular genetics at Emory University and completed his postdoctoral fellowship in pharmacology at the LSU Health Sciences Center in New Orleans. Dr. Blumer’s research efforts are focused on identifying the roles of accessory proteins for heterotrimeric G-protein signaling systems, specifically the Activator of G protein Signaling (AGS) proteins AGS3 and AGS4, within the context of GPCR signaling, particularly that of chemokines. He is the Theme Leader for the Molecules, Metabolism, and Therapeutics (MMT)

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theme, Course Director for the Respiratory/Renal/ Acid-Base course, and Course Co-director of the Cardiovascular course in the MUSC College of Medicine. He has been actively involved in dental and graduate school teaching as well. A 20-year member of ASPET, Dr. Blumer has served on the Executive Committee and as Secretary/Treasurer for the Division for Molecular Pharmacology and currently serves on the Executive Committee and as Secretary/Treasurerelect for the Division for Pharmacology Education. He also represents ASPET on the AAMC-Council of Faculty and Academic Societies (AAMC-CFAS) and serves as an Associate Editor for the Journal of Pharmacology and Experimental Therapeutics. Dr. Blumer is a Distinguished Teaching Scholar in the MUSC Academy of Medical Educators and has received numerous teaching awards, including five Golden Apple Teacher of the Year awards in the MUSC College of Medicine. Dr. Khalil Eldeeb is an Associate Professor of Pharmacology at Campbell University Jerry M. Wallace School of Osteopathic Medicine (CUSOM). He earned a Medical Degree and a Master’s in pharmacology with distinction from Al-Azhar University in Egypt, then a PhD in pharmacology from the University of Nottingham, UK. Dr. Eldeeb completed a research/teaching postdoctoral scholarship at Wake Forest University School of

Medicine among the first cohort of the Postdoctoral Research, Instruction, and Mentoring Experience (PRIME) program. He completed the Health Equity Research Opportunity (HERO) Fellowship at Wake Forest University and the International Association of Medical Science Educators (IAMSE) Fellowship. His research findings investigating cannabinoid receptors and associated proteins were published in peer-reviewed and high-impact journals and presented at different international conferences. His health/medical education research identifies student learning, instruction, and success features presented at the ASPET and IAMSE meetings. Dr. Eldeeb has been a member of the British Pharmacological Society for 14 years and ASPET for 10 years. He is the recipient of the BPS Schechter Award, IAMSE Faculty Travel Award, CUSOM Dean’s Award for Excellence in Research, and ASPET Pharmacology Educator Award. Dr. Eldeeb is a National Faculty for Pharmacology at the National Board of Osteopathic Medical Examiners (NBOME), member of the IAMSE educational scholarship Committee, the British Pharmacological Society (BPS) Awards Panel, the BPS International Advisory Group, and Executive Committee of the Division for Pharmacology Education at ASPET. Dr. Teresa Wilborn is a Professor and Vice Chair of the Department of Pharmacology and Toxicology at the University of Alabama at Birmingham (UAB) where she is the discipline lead for pharmacology in the medical curriculum. She instructs dental, optometry and

graduate students at UAB and recently led the design of pharmacology courses for the Multidisciplinary Biomedical Science program. Dr. Wilborn received a BS in pharmacy from the University of Florida, a PharmD from Mercer University and a PhD in pharmacology from UAB. She completed a fellowship in renal physiology sponsored by the National Kidney Foundation. Dr. Wilborn was previously on the faculty at Samford University where she taught pharmacy, nurse anesthesia, and nurse practitioner students. She also led a studies abroad course, Healthcare in Great Britain, for several years, and participated in a Latin American Fellows Program focused on enhancing cultural competency. She has served on the USMLE Pharmacology and Biochemistry Test Development Committee for the past four years and was recently asked to serve on the USMLE Interdisciplinary Review Committee. Dr. Wilborn enjoys creating online interactive pharmacology content and recently participated in designing an online game, EndoFlix, using the Kaizen-Education platform to increase student engagement during the COVID-19 pandemic. She has received numerous teaching awards at the UAB School of Medicine including Best Educator Awards for the Fundamentals of Medicine course, the best educator award for the Reproductive curriculum, and the Dale Benos Award for Excellence in Education. The Division for Pharmacology Education appreciates Dr. Blumer, Dr. Eldeeb and Dr. Wilborn for their many contributions to the discipline. The Academy of Pharmacology Educators is pleased to add these educator-scholars to the roster.

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Thummel and Paine Share Thoughts on the Importance of Mentorship Through DMDD Submitted by Lindsay C. Czuba, PhD and Andrew Rowland, PhD For over 20 years, Ken Thummel, PhD, has been actively involved both in ASPET and the Division of Drug Metabolism and Disposition (DMDD). During this time, he was President of ASPET in 2014 and the recipient of the 2022 Bernard B. Brodie Award. As a professor and former chair in the Department of Pharmaceutics at the University of Washington, he has served as both a formal and informal mentor to many early career researchers over the years. One of his former mentees, Mary Paine, PhD, is now a Professor in the Department of Pharmaceutical Sciences at Washington State University and serves as an Associate Editor of Drug Metabolism and Disposition. She leads the Center of Excellence for Natural Product Drug Interaction Research, where she mentors a highly collaborative, and multidisciplinary team of researchers and junior scientists. In this interview, Ken and Mary discuss their mentoring style, creating a respectful training environment, and providing insight for establishing long-lasting and collaborative mentor-mentee relationships.

How has your definition and approach to mentorship evolved over your careers? KT: When my career began, I had a top-down approach to mentoring graduate students. I was often in the lab alongside my students yet felt acutely the pressures to succeed at securing grant funding and publications. While I did interact with my first trainees like Mary Paine frequently, I probably did not give them sufficient time to work through inevitable methodological problems, imposing recommendations from my past experience. They were often the correct actions, but that didn’t do much to foster selfconfidence and intellectual growth in the trainees. My approach to mentoring changed with time, in part because of increasing administrative demands that prevented the kind of close interactions I had with trainees earlier in my career. This change helped foster greater independence in trainees who were poised to take more initiative and didn’t necessarily need the benefits of daily interactions. I came to rely on the creative energies of my trainees in charting project

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Ken Thummel, PhD

Mary Paine, PhD

directions and bringing novel technical expertise to the action plans. On reflection, I think that some trainees benefitted from this type of mentor-mentee interaction experience, but others did not. As I moved away from administrative commitments in recent years, I tried to customize my mentormentee relationship to best suit what I think are the strengths and weaknesses of the individual and areas of necessary growth. I strive to create a truly impactful learning experience built on respect and the needs of the trainee, rather than my own ambitions. MP: As I believe is still largely the case for even young principal investigators, you learn how to be an effective mentor on-the-job. Since establishing my own lab nearly 20 years ago, I would describe my mentoring approach to be more middle-out, as I profess not to know more than my trainees. Early in my career, I found that meeting with each trainee one-on-one regularly at least every two weeks is an effective way to learn of their strengths and weaknesses, as well as get to know them personally. Having this knowledge early during their time in the graduate program allows me to tailor my mentoring approach to maximize their chances of success, as no one approach is applicable to all. Mentoring is a two-way street that requires mutual respect. I learn from them as much as they learn from me. I sometimes seek their advice when I encounter certain difficult issues, as gaining an understanding from a younger, different perspective can help me better formulate a resolution plan.

What advice would you give to junior scientists looking to establish a strong mentor-mentee relationship? KT: Listen and match mentoring advice to what you think they need in the short- and long-term. Be willing to give the mentee time to absorb and change and accept to the extent possible stylistic differences. Embrace opportunities for joint mentoring that provides the mentee with invaluable complementary expertise. Support mentee requests for additional didactic and experiential training. Enrich their education however possible. MP: Be willing to devote regular quality, one-on-one time with each trainee. Respect and learn from them to improve your mentoring style. Confront and talk through any conflicts as soon as possible. Respond to their questions and requests in a timely manner. Encourage them to apply for funding opportunities, such as fellowships and travel grants, to gain writing skills that will help them sell themselves to review panels and even prospective employers. Ensure regular social interactions with your research team to maintain positive group dynamics.

Reflecting on your history as a graduate mentor-mentee pair through to your present interactions as collaborators, in what ways has your relationship both stayed similar and how has it evolved? KT: As Mary has progressed through her career, I have continued to try and open doors whenever the opportunities have presented themselves, recommending her for positions in our professional society, academic positions, and research collaborations based on her strengths and interests, which I believe I know well. Her success is incredibly rewarding to me. While I am always there to offer her advice, no matter how important or trivial the issue, I keep that private and carefully avoid interjecting my opinions on strategic issues in public unless she explicitly asks me. She has good instincts and strong leadership skills and appears to be a great mentor in her own right.

MP: Ken’s thirst for new and exciting scientific knowledge was readily apparent when I first joined his lab in the early 1990s, and his zeal has not changed. He has maintained his uncanny ability to take the seemingly most uninteresting set of data and turn it into a positive. Our mentor-mentee relationship has matured exponentially over the years and has only strengthened since I moved back to Washington state and became collaborators on an exciting NIH center grant focused on natural product-drug interactions. I have learned a lot from him about strategic ways to lead a large multi-investigator, multi-site grant to deliver the best product possible while meeting annual grant milestones. I take comfort in knowing that I can always call upon him when I need his sage advice. I value his mentorship more and more each day.

How has your involvement with ASPET/ DMDD helped you become a better mentor? KT: Participation in the Division and Society has given me numerous opportunities to learn from other mentor-mentee pairs that I have encountered at national meetings and other venues. There have been some wonderful role models to emulate – training success takes many different forms. It is the final product that matters. When I witness the professional success of a trainee during a scientific presentation or in a nascent leadership role, I ask myself, “How did they get there and what role did the mentor play in bringing them to that stage of accomplishment”? I find those successes equally enriching as my own. MP: Like Ken, my participation in the division and society has afforded me many opportunities to observe other successful mentor-mentee pairs at societal and other (inter)national meetings. I strive to give credit where credit is due, and one cue I have taken from other mentors is to place a picture of a trainee on the relevant PowerPoint slide(s) whenever I am presenting data they generated. Not only does this signify my pride for these individuals, but it gives them greater recognition for their accomplishments. I have learned that publicly crediting and thanking trainees for their hard work is fundamental to effective mentorship.

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2022 ASPET Young Scientist Award Winners The ASPET Student/Postdoctoral Poster Competition was held Sunday, April 3, during the ASPET Annual Meeting at EB 2022 in Philadelphia, Pa. Of the 143 members selected to compete, the following are the poster award winners. Additionally, several divisions held oral competitions for young scientists on Monday, April 4. These winners are also recognized.

2022 Shockley Competition Winners The 2022 Dolores C. Shockley Competition took place at the Student/Postdoctoral Poster Competition. Dr. Shockley was the first African American woman to earn a PhD in pharmacology and the first to be appointed to chair a pharmacology department in the United States. In the undergraduate student category, prizes were awarded to Kennedy Outlaw, (1st place) from Purdue University and Suzannah De Almeida (2nd place) from University of Connecticut. In the postbaccalaureate/graduate student category, prizes were awarded to Nathalie Momplaisir (1st place) from the University of Michigan, Carolina Caban Rivera (2nd place) from the Lewis Katz School of Medicine at Temple University and Nina Beltran (3rd place) from the University of Texas at El Paso.

2022 ASPET Division Award Winners Division for Behavioral Pharmacology

Student/Postdoctoral Poster Competition In the undergraduate category, prizes were awarded to Sarah Mott (1st place) from the University of South Carolina School of Medicine and Francesca Asmus (2nd place) from the University of New England. In the postbaccalaureate/graduate student category, prizes were awarded to Brittany Pope (1st place) from the Wake Forest School of Medicine, Dalal Alkhelb (2nd place) from the Center of Drug Discovery, Northeastern University, and Carolina Caban Rivera (3rd place) from the Lewis Katz School of Medicine at Temple University.

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Postdoctoral Showcase (Oral Sessions) The winner of the Division for Behavioral Pharmacology Postdoctoral Showcase was Briana Mason from the University of Texas Health Science Center at San Antonio.

Division for Cancer Pharmacology

Student/Postdoctoral Poster Competition In the postbaccalaureate/graduate student category, prizes were awarded to Nicole Ramos Solis (1st place) from Indiana University, School of Medicine, Arthur Chow (2nd place) from the Icahn School of Medicine at Mount Sinai and Pravita Balijepalli (3rd place) from the Washington State University. Young Investigators Symposium (Oral Sessions) In the postdoctoral category, “finalist” prizes were awarded to Jeffrey Rappaport from the Albert Einstein College of Medicine, Dayn Godinez from Texas A&M University, Tinslee Dilday from the Indiana University School of Medicine, and Lishu He from the Medical College of Wisconsin.

Division for Cardiovascular Pharmacology

Student/Postdoctoral Poster Competition In the undergraduate category, the top prize was awarded to Alec Horton (1st place) from Tulane University, School of Medicine. In the postbaccalaureate/graduate student category, prizes were awarded to Robert Valencia (1st place) from the University of Alberta, and Norton Cheng (2nd place) from the University of California, San Diego. In the postdoctoral category, the top prize was awarded to Zdravka Daneva (1st place) from the University of Virginia. CVP Trainee Showcase (Oral Sessions) In the graduate student category, prizes were awarded to Ama Okyere (1st place) from Temple University and Kimberly Ferrero (2nd place) from Lewis Katz School of Medicine at Temple University. In the postdoctoral category, prizes were awarded to

Gustavo Oliveira de Paula (1st place) from the Albert Einstein College of Medicine and Ahmed Alarabi (2nd place) from Texas A&M University.

Division for Drug Discovery and Development

Student/Postdoctoral Poster Competition In the undergraduate student category, prizes were awarded to Irene Corona-Avila (1st place) from Albion College and Mary Fiala (2nd place) from the University of Nebraska at Kearney. In the postbaccalaureate/graduate student category, prizes were awarded to Caitlin Risener (1st place) from the Emory University School of Medicine, Lea Stitzlein (2nd place) from Anderson Cancer Center, and Kathryn Braden (3rd place) from Saint Louis University.

In the postbaccalaureate/graduate student category, prizes were awarded to Blair Willette (1st place) from Duke University, Clara Posner (2nd place) from the University of California, San Diego, and Khairunnisa Semesta (3rd place) from Duke University. In the postdoctoral category, prizes were awarded to Francesco De Pascali (1st place) from Thomas Jefferson University, Omar Hamed (2nd place) from the Cumming School of Medicine, University of Calgary, and Tomoka Gose (3rd place) from St. Jude Children’s Research Hospital. Postdoctoral Scientist Award Competition (Oral Sessions) In the postdoctoral category, prizes were awarded to Isaac Fisher (1st place) from Purdue University, Yu-Chen Yen (2nd place) from Purdue University, and Dipak Patil (3rd place) from the Scripps Research Institute.

Division for Neuropharmacology

Division for Drug Metabolism and Disposition

Student/Postdoctoral Poster Competition In the postbaccalaureate/graduate student category, prizes were awarded to Colten Eberhard (1st place) from Johns Hopkins University, Austin Sun (2nd place) from the University of Washington, and Eric Mosher (3rd place) from Johns Hopkins University School of Medicine. In the postdoctoral category, prizes were awarded to Ryan Seguin (1st place) from the University of Washington, Jonghwa Lee (2nd place) from the University of North Carolina at Chapel Hill Eshelman School of Pharmacy, and Patrick Connick (3rd place) from the Louisiana State University Health Sciences Center.

Division for Molecular Pharmacology

Student/Postdoctoral Poster Competition In the undergraduate student category, prizes were awarded to Chloe Hicks (1st place) from Duke University and Kennedy Outlaw (2nd place) from Purdue University.

Student/Postdoctoral Poster Competition In the undergraduate student category, prizes were awarded to Suzannah De Almeida (1st place) from the University of Connecticut and Taylor Quintana (2nd place) from California State University, East Bay. In the postbaccalaureate/graduate student category, prizes were awarded to Jason Wickman (1st place) from Drexel University, Leah Salinsky (2nd place) from the University of Texas Medical Branch, and Kimberly Thibeault (3rd place) from Vanderbilt University. In the postdoctoral category, prizes were awarded to Akila Ram (1st place) from Utah State University, Dino Luethi (2nd place) from the University of Basel, and Deborah Rudin (3rd place) from the University Hospital Basel. Postdoctoral Scientist Award Competition (Oral Sessions) In the Postdoctoral category, prizes were awarded to Stephanie Matt (1st place) from Uniformed Services University, Karan Muchala (2nd place) from the University of Cincinnati, Deborah Luessen (3rd place) from Texas Tech University Health Sciences Center, and Shalini Dogra (honorable mention) from Vanderbilt University.

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Division for Pharmacology Education

In the undergraduate student category, the top prize was awarded to Andrea Mosquera (1st place) from Rutgers University. In the postbaccalaureate/graduate student category, prizes were awarded to Nicholas Conway (1st place) from the Herbert Wertheim College of Medicine, Florida International University and Yasmin Elsobky (2nd place) from Alexandria University.

Division for Toxicology

Student/Postdoctoral Poster Competition In the postdoctoral category, prizes were awarded to Emily Stevenson (1st place) from Rutgers, The State University of New Jersey, Yuting Yuan (2nd place)

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from Johns Hopkins University School of Medicine, and Ashley Cox (3rd place) from the Marshall University School of Medicine.

Division for Translational and Clinical Pharmacology

Student/Postdoctoral Poster Competition In the postbaccalaureate/graduate student category, the top prize was awarded to Sushrut Shah (1st place) from Thomas Jefferson University. Young Investigator Awards Platform (Oral Sessions) In the graduate student category, prizes were given to Manisha Pradhan from Johns Hopkins University, Shubham Soni from the University of Alberta, and Piyush Padhi from the University of Georgia. In the postdoctoral category, prizes were given to Jia Nong from the University of Pennsylvania and Shanshan Wang from the University of California, San Diego.

Meet us in St. Louis! St. Louis Union Station Hotel May 18–21

St. Louis Union Station Hotel May 18–21

The Pharmacologist June 2022

Articles inside

Division News

Chapter News

Membership News

Education News

Journals News

Feature Story: Lithium: Battering mania

EB 2022 Wrap up

Call for 2023 Award Nominations

Science Policy News

2022 Annual Meeting Highlights

Message from the President