A Conversation with John R. Hepler, PhD
John R. Hepler is a Professor and Vice-Chair for Academic Affairs in the Department of Pharmacology and Chemical Biology at the Emory University School of Medicine. He currently serves as Secretary/Treasurer-elect for ASPET. Dr. Hepler received his BA in chemistry and PhD in neurobiology from the University of North Carolina at Chapel Hill studying molecular pharmacology under Dr. T. Kendall Harden. For his postdoctoral training, he studied G protein signaling pathways under Dr. Alfred G. Gilman at the University of Texas Southwestern Medical Center. Dr. Hepler then joined the faculty at Emory University in 1996 and has been a full Professor with tenure since 2010. He has been a member of ASPET since 1999 and served as Secretary-Treasurer of the Molecular Pharmacology Division of ASPET in 2009–2010, and then as Chair of the Molecular Pharmacology Division in 2021–2022. He has served on the Editorial Board of Molecular Pharmacology since 2002, as well as Associate Editor since 2012, and Deputy Editor from 2015–2017.
How did you get started in pharmacology?
I’ve been immersed in pharmacology from my earliest days in science. I entered graduate school in 1983 in neuroscience at the University of North Carolina at Chapel Hill. Prior to that, I worked as a research technician on campus in a lab that did neuroscience research exploring causes of alcohol addiction using whole animal models. That inspired me to pursue graduate school research in neuroscience, but my first research rotation was in the laboratory of Dr. T. Kendall (Ken) Harden in the Pharmacology Department studying receptor/G protein and second messenger signaling. That was, and still is today, molecular pharmacology. I fell in love with the research, and I eventually joined the Harden lab with Ken as my mentor/advisor. I was fortunate to have him as a mentor and be in his lab at the time when he was a young assistant professor. He grew into a towering figure in molecular pharmacology and ASPET, serving as Chair of the Board of Publications Trustees, on the editorial boards of two ASPET journals (including as Editor-in-Chief of Molecular Pharmacology) and is a deserving ASPET Fellow (FASPET). Thankfully, we remain close friends to this day.
My work in Ken’s lab launched my career in the field of molecular pharmacology. I continued in 1989 with my postdoctoral research with Dr. Alfred G. Gilman, Chair of Pharmacology and Nobel prize winner (1994) at UT Southwestern Medical Center. His lab was the world leader in G protein signaling pathways, which I studied. Again, this was molecular pharmacology and those positive experiences, immersed in pharmacology labs and departments, set the foundation for my independent career at the Emory University School of Medicine.
In 1996, I joined the Department of Pharmacology (now Pharmacology and Chemical Biology) at Emory studying receptor, G protein and RGS protein signaling pathways in the context of synaptic signaling linked to synaptic plasticity, learning and memory and addiction.
How did you first get involved with ASPET?
The very first scientific meeting I attended as a young graduate student was the FASEB meeting, which included ASPET. My graduate advisor, Dr. Ken Harden, was actively involved with ASPET and we published some of our most interesting work in ASPET journals. I attended Experimental Biology/ASPET meetings as a postdoc and joined ASPET as a full faculty member in 1999, after which I got involved with the Molecular Pharmacology Division. I’m still here over 25 years later.
What do you want the ASPET membership to know about you and your ideas on how to move the organization forward during your term?
I plan to work with Council to advance ASPET’s strategic goals aimed at enhancing member experiences at annual meetings, stabilizing and growing the journals, stabilizing society finances, attracting new members, and advocating for science and pharmacology. ASPET is the leading professional society and natural home for all pharmacologists/toxicologists in America and around the world, whether they work in industry, academia, biotech, government, regulatory affairs, or for non-profits. I want young scientists to know and understand ASPET’s role, and for ASPET to clearly communicate to the next generation of pharmacologists its value to them in terms of professional development, presenting their findings to the world, networking, and science advocacy.
Science today in general is under attack in unprecedented ways, and ASPET is an authoritative voice and advocate for science. We on Council want to support and encourage our ASPET public affairs team in their efforts to champion and educate lawmakers and the general public about the many essential contributions and benefits that scientific discovery research in pharmacology/toxicology brings to our nation.
I also think it is vital for young scientists to get involved with ASPET and science advocacy, and we on ASPET Council want to provide opportunities and support for that to happen.
What has been your proudest accomplishment in your career so far?
My proudest accomplishments fall into two arenas: research and graduate education. In my research, I spent my early years as a graduate student and postdoc searching for the mystery G protein(s) that linked cell surface receptors to inositol phosphate/calcium signaling. This was unknown at the time. It was a great thrill when we were finally able to identify and characterize the new G protein family (Gq, 11, 14 and 15) that coupled receptors to phospholipase C. This was followed by studies of a new family of protein regulators of G protein signaling (the RGS proteins) that negatively regulated receptor/G protein signaling. These discoveries helped launch my independent research career studying the signaling diversity of Gq family members and how RGS proteins selectively and preferentially pair up with and couple to receptor/G protein pairs. This was followed by our work showing that certain RGS proteins (e.g. RGS14) act as complex multifunctional integrators of G protein, Ras/Erk, and Calcium/CaM/CaMK signaling pathways important for synaptic plasticity linked to learning and memory.
In parallel with my research, I’ve been passionate about graduate education, and I’m very proud of the many graduate students I’ve had the great fortune to advise or mentor directly, and the successful and productive careers they have gone on to enjoy.
What advice would you give young scientists who are just starting out in their careers?
For this question, I assume the audience is new graduate students. My advice is multifold.
First, embrace the thrill of discovery, no matter how small. The majority of discoveries are incremental, but still very important to the big picture. Biomedical research is a multi-million-piece jigsaw puzzle and every piece is important.
Learn to be OK with failure, as many experiments fail. Failed experiments are still useful information if technically sound.
Learn to be resilient. Science does not involve immediate gratification, but is very satisfying when the discoveries are made.
Keep an open mind about research. Don’t be too focused or committed to a certain research topic or lab/mentor at this stage. You don’t yet know what you don’t know. You will discover new areas of biomedical science that will interest or excite you. Scientists are naturally curious so you should be excited by many potential topics of study, not just one.
View graduate school as an opportunity to become a highly trained professional with highly desirable skills that are transferable to many work situations. For example, you can understand any biomedical article, or you have analytical, writing and communication skills that are very desirable. Of course, this assumes you don’t use AI as a crutch/substitute for “learning” those skills.
View faculty as positive resources and as your colleagues, not adversaries. The purpose of graduate school is to become an independent professional scientist—you are an apprentice. Finding a good mentor(s) to help you on that journey is more important than the research topic (but still choose a research topic that excites you). Related to this, over the course of your career, your research will change as you follow new discoveries, so embrace that idea of being open early (follow the discovery) and don’t get too stuck in one topic. Keep an open and curious mind.
The course work and grading in graduate school is designed for you to learn, not to worry about grades. Take advantage of that and don’t succumb to the new lure of AI as a crutch and substitute for learning.
Finally, start exploring the range of career options in Year 1 and learn about them. Hopefully, you will be exposed to professional development classes in school that will do that, but ASPET certainly offers many career seminars/workshops. Ask yourself, what should I be doing now on the side, while in graduate school, to be competitive in that career in five or ten years?
Dr. Hepler’s research has focused on understanding how receptors (GPCRs), G proteins and RGS proteins work together to regulate cell and organ physiology. His early research helped to define how cell surface receptors mobilize the novel (at the time) second messengers InsP3 and calcium. He played key roles in the original discovery and characterization of the Gq class of G proteins that link receptors to activation of phospholipase C and InsP3 formation, and their regulation by lipid modifications and RGS proteins. His research at Emory is focused on understanding the regulation of neurotransmitter and hormone receptor signaling by G proteins and RGS proteins. Relating to this, Dr. Hepler was Co-Organizer and Chair of the 2011 ASPET Colloquium on “RGS and AGS proteins in physiology and disease.” His research has identified previously unknown mechanisms whereby GPCR/G protein/RGS proteins selectively assemble into preferred functional complexes to carry out their signaling. Subsequent studies explored downstream signaling roles for multifunctional RGS proteins, their genetic variants, and binding partners. His work defined RGS14 as a novel integrator of G proteins, Ras/Raf/ERK and Ca++/Calmodulin signaling in neurons that regulates postsynaptic plasticity linked to learning and memory, reward/addictive behaviors, and neuroprotection following seizure-induced neuronal injury. His recent collaborative studies have identified RGS14 as a newly appreciated regulator of kidney functions linked to chronic kidney disease.
Dr. Hepler also has a long-standing commitment to graduate education and actively teaches and leads in the Emory Neuroscience, Pharmacology, Biochemistry and Cell Biology Training Programs, receiving a Teaching Excellence Award in 2016. He has served as Director of Graduate Studies for both the Pharmacology and the Neuroscience graduate programs at Emory, received the PhRMA New Investigator Award in 1997 and was elected as a Fellow of AAAS (FAAAS) in 2014 and Fellow of ASPET (FASPET) in 2024. Over his career, he has authored/co-authored over 110 publications, served on numerous federal, private, and academic advisory review boards, and has delivered dozens of invited lectures nationally and internationally.
