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<< Back to podcast list Strategic Partner(s) Sri Kosuri About Dr. Sri Kosuri Sri is a biologist that has helped build technologies, labs, and companies in synthetic biology, functional genomics, and bioinformatics over the last 20 years. He is passionate about developing more rational ways to understand and engineer biology. Sri is a co-founder at Octant and an Associate Professor at UCLA in the Chemistry and Biochemistry Department. His lab has worked on building large-scale ways of empirically exploring questions in protein biochemistry, human genetic variation, gene regulation, chemical biology, synthetic biology, and functional genomics. Sri previously worked at the Wyss Institute and Harvard, where he built numerous technologies in gene synthesis, DNA information storage, gene editing, and large-scale multiplexed assays. He helped build Gen9, a gene synthesis company, as a member of the SAB and was the first employee of Joule Unlimited, an engineered algal biofuel company. He is a Searle Scholar (2015), NIH New Innovator (2014), and received his ScD in Biological Engineering at MIT and BS in Bioengineering at UC Berkeley. Sri is originally from New Jersey, Philadelphia, and Kansas and was born in North Carolina. He enjoys eating, getting outdoors, and traveling with his wife and two children. Dr. Sri Kosuri on the web Octant Kosuri Lab Twitter LinkedIn Dr. GPCR Ecosystem Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Dr. Katarzyna Marcinkiewicz About Dr. Katarzyna Marcinkiewicz "Katarzyna is a Senior Editor at Nature Communications, which she joined in April 2020, following three years on the editorial teams of Nature Structural and Molecular Biology and Nature Biotechnology. She obtained her Ph.D. from Weill Cornell Graduate School of Medical Sciences in New York City, studying epigenetic changes in cancer. During her postdoctoral training at New York University School of Medicine, her research focused on cellular senescence. Katarzyna handles submissions in structural biology, biophysics and biochemistry, with a particular focus on membrane proteins and protein folding." Dr. Katarzyna Marcinkiewicz on the web LinkedIn Nature The Spectator Dr. GPCR Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Dr. GPCR Board About Dr. Yamina Berchiche "Dr. Yamina A. Berchiche is the founder of Dr. GPCR, an ecosystem designed to bring together stakeholders interested in using G-Protein Coupled Receptors (GPCRs) that control virtually everything in the body as drug targets. The mission of Dr. GPCR is to accelerate GPCR drug discovery by sharing the latest research and technology advances in the field and providing exposure to scientists through the Dr. GPCR podcast. Dr. Berchiche obtained her Master’s and Ph.D. in Biochemistry at the University of Montreal in Canada before training at Rockefeller University in New York and the National Institutes of Health in Bethesda, Maryland. She developed expertise over the past two decades studying structure/function relationships of GPCRs using live-cell bioluminescence resonance energy transfer (BRET). Her work focused on chemokine receptors, members of the GPCR family that control cell movement in the body." Dr. Yamina Berchiche on the web Website LinkedIn Facebook Twitter ResearchGate PubMed Google Scholar Dr. GPCR About Dr. Maria Waldhoer "I am a pharmacologist with a ~30 years background in academia and industry, working both in big pharma and biotech settings. My experience in basic research at several universities worldwide and early R&D at Novo Nordisk A/S allowed me to shape a swiss start-up company from a scientifc idea to a thriving Biotech focusing on Systems Biology & AI to accelerate the quest for novel & safer drugs on GPCRs. After a well needed break from the grind, I am now a scientific/business consultant for clients both in Academia and in the Life sciences and Healthcare industry. I am a recent convert and strong advocate for integrating mindfulness and mental wellbeing into demanding work routines." Dr. Maria Waldhoer on the web LinkedIn T witter Pubmed Dr. GPCR About Dr. JoAnn Trejo "Dr. JoAnn Trejo earned her Ph.D. at UC San Diego. She completed her postdoctoral fellowship at UC San Francisco under the guidance of Professor Shaun Coughlin where she worked on the newly discovered protease-activated GPCRs. Dr. Trejo joined the faculty in the Department of Pharmacology at the University of North Carolina in 2000 and then moved to UC San Diego School Medicine, Department of Pharmacology in 2008, where she quickly rose through the ranks to tenured professor in 2012. In 2014, she was appointed Vice-Chair of the Department of Pharmacology. The long-term goal of Dr. Trejo’s research program is to gain a thorough and mechanistic understanding of processes that control cell signaling by protease-activated receptors (PARs) and the impact on vascular inflammation and cancer progression. PARs are GPCRs that are activated through an atypical irreversible proteolytic mechanism. The precise control of PAR signaling is critical for proper temporal and spatial dynamics of signaling and appropriate cellular responses. Discovering new aspects of PAR signaling is important for increasing the fundamental knowledge of GPCR biology and for the identification of drug targets and future drug development. Dr. Trejo’s research has focused on PAR1, which has important functions in hemostasis, thrombosis, inflammation, and cancer and is an important drug target. She has made numerous important discoveries related to the mechanisms that control PAR1 signaling and closely related family members and published extensively on this topic. Dr. Trejo has been continuously funded by the NIH for >20 years and was a recipient of the prestigious American Heart Association Established Investigator Award. Her laboratory is the recognized expert on protease-activated receptors, particularly PAR1, and over the years she has discovered novel aspects of GPCR biology, acquired critical expertise, and rigorous approaches to examine PAR1 function using human cultured cells and mouse models. Dr. Trejo has presented her studies at 52 national/international meetings and 66 academic seminars across the U.S." Dr. JoAnn Trejo on the web UC San Diego Trejo Lab Wikipedia LinkedIn Google Scholar Orcid Twitter UC San Diego School of Medicine Researchgate Dr. GPCR About Anne Marie Quinn "Anne Marie Quinn has a long and varied work experience in the biocomputing and bioinformatics fields. From 1987 to 1994, they were the Director of Biocomputing at The Salk Institute, where they managed institute-wide network and biocomputing services, served on the Steering Committee of the San Diego Supercomputer Center, and provided consultation for genetic sequence analysis, molecular modeling and database searching. In 1994, they became a Bioinformatics Scientist at CuraGen Corporation. From 1995 to 2002, they worked at Yale University School of Medicine as the Bioinformatics Core Facility Manager, where they managed a technical support team providing scientific data analysis and database development services, contributed analytic support resulting in authorship of numerous scientific publications and new funding, and developed and co-taught a new course in bioinformatics for graduate students. From 2002 to 2006, they were a Senior Application Scientist at Accelrys, where they were the technical point of contact for customers assessing features of software products for drug discovery and genomic analysis, delivered technical presentations and software demonstrations to prospective customers worldwide, and developed web-based case notes, marketing seminars and product literature for scientific software. Finally, since 2006, they have been the Chief Executive Officer at Montana Molecular, LLC. Anne Marie Quinn attended Yale University from 1998 to 2000, where they earned a Master of Public Health (MPH) degree in Biostatistics and Bioinformatics. Prior to that, they obtained a Bachelor of Arts (B.A.) degree from California State University, Long Beach in 1982." Anne Marie Quinn on the web Google Scholar The Org LinkedIn Twitter Dr. GPCR Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Self-Learning, Collaboration, and Delegation in Science with Dr. Badr Sokrat About Dr. Badr Sokrat " After completing my undergraduate studies with an internship in the laboratory of Dr. Christian Baron studying bacterial secretion systems, I joined the molecular pharmacology laboratory of Dr. Michel Bouvier at the University of Montreal. There, I completed a PhD in biochemistry exploring the non-canonical functions and possible novel mechanisms of regulation of β-arrestin following GPCR activation. Among other projects, I studied the role of β-arrestin in G protein trafficking, the impact of GPCR ubiquitination on signaling and β-arrestin functions, and the characterization of novel β-arrestin interactors. At the end of 2023, I joined the research group of Dr. Nigel Bunnett at the NYU Pain Research Center as a postdoctoral researcher. My current research focuses on investigating GPCR signaling and trafficking in the context of inflammation and chronic pain. I am particularly interested in spatial signaling bias or how GPCRs can redistribute to different subcellular compartments to trigger distinct signaling events. " Dr. Badr Sokrat on the web PubMed ResearchGate LinkedIn Dr. GPCR AI Summary AI-generated content may be inaccurate or misleading. Always check for accuracy. Quick Recap Yamina and Badr discussed their backgrounds in science, their experiences in education, and the challenges of competition and mental health in their home province of Quebec. They also discussed Badr's career trajectory, the importance of self-learning, collaboration, and delegation in scientific research, and the need for a well-organized lab manager in their global scientific team. Lastly, they highlighted the challenges scientists face in academia and industry, the importance of projection and careful communication, and the potential for future collaboration. Next Steps Badr will continue focusing his research on GPCRs involved in pain and inflammation during his postdoc at NYU. Yamina and Badr will create a virtual genealogical tree mapping the connections between researchers in the GPCR field. Yamina will continue to develop and manage the Dr. GPCR University podcast, focusing on collaboration and learning opportunities for the GPCR community. Yamina will balance her scientific work with personal interests and activities to maintain a healthy work-life balance. Summary Podcast Recording and Science Backgrounds Yamina and Badr discussed recording their podcast with Samary Eye, who made a humorous error in transcribing "Edmond" as "agendie". They then shared their backgrounds and interests in science, with Badr recounting his journey from struggling with math in an engineering physics degree to excelling in biology and obtaining a Master’s degree in biochemistry. Badr worked in various science labs, including Dr. Christian Badr’s and Dr. Philip Woozab’s, focusing on bacterial secretion systems, GPCRs, and bioinformatics. Yamina, who also attended the University of Montreal, confirmed her interest in science and mentioned their shared passion for the subject. Education, Competition, and Mental Health Discussion Badr and Yamina shared their experiences about their education, with Yamina sharing her struggles during her first trimester in college and her eventual success due to the support of a theater group and a good teacher. They both discussed the intense competition in their home province, Quebec, and its impact on students' mental health and university admission prospects. They also talked about the negative aspects of this competition, such as students putting others down, and how it can be toxic. Lastly, Badr shared his transition into the field of GPCRs.. Badr recounted Badr's Journey, Multiplexing Assays, and Collaboration Badr shared his learning process and early tasks at Michelle’s lab, which involved creating stable cell lines and identifying potential protein interactions. He described a significant moment when he confirmed a previously uncertain interaction, underscoring the importance of confidence and motivation in scientific discoveries. Yamina emphasized the potential of multiplexing assays in expanding the scope of scientific exploration and finding new protein interactions. They also discussed the concept of serendipity in scientific research, illustrating with examples of Kathleen Curran and her father. Lastly, they concurred on the collaborative nature of the scientific community, where scientists build upon each other's work. Badr's Postdoc Plans and GPCR Research Yamina and Badr discussed Badr’s career trajectory and his decision to pursue a postdoc abroad after his PhD. Badr shared his passion for GPCR signalling and regulation, specifically in the context of pain and inflammation, and how his PhD research on non-canonical GPCR roles laid the foundation for his postdoc work. He also explained his strategy for finding a suitable postdoc lab, which involved reaching out to labs whose recent research aligned with his interests. Lastly, Badr emphasized the importance of choosing a city one would like to live in for several years when deciding on a postdoc position. Badr’s Journey to Overcoming Confidence Fluctuations Badr shared his journey of overcoming fluctuating confidence levels during his PhD journey, emphasizing the importance of viewing failures as valuable learning opportunities. He highlighted that he had to regain his confidence after a period of three failed experiments. Yamina expressed interest in understanding how Badr’s experiences influenced his current role, and Badr stressed the need for individuals to develop challenges outside of their work environment to foster greater confidence. Additionally, they both agreed on the importance of mentorship in building confidence, with Yamina sharing her positive experience of being advised by her supervisor, Nikolaos. Self-Learning, Collaboration, and Delegation in Science Badr and Yamina discussed the importance of self-learning and scientific confidence in managing projects and conducting experiments. They highlighted the significance of collaboration and delegation in scientific research, noting that knowing when to ask for help and when to delegate tasks can lead to more efficient and successful results. Yamina shared her experiences of starting a project independently and then delegating tasks, while Badr shared his plans for his current project, which involved learning certain techniques himself and delegating others to colleagues. They both agreed on the value of these strategies. Yamina’s Podcast Journey and Career Advice Yamina discussed how her podcast on chemokine ligands led to new collaborations and published work. She emphasized preparation and understanding guests’ backgrounds for engaging interviews. Yamina shared her experiences at Rockefeller, where she studied chemical receptors. She aims for Dr. GPCR to serve as a global hub for the GPCR community. Badr expressed interest in broadening his skills beyond the lab, such as project management and effective communication. Yamina advised him to consider career options after his postdoc and adapt to different systems. She highlighted the importance of learning behind-the-scenes skills and staying informed through resources like GPCR news. Improving Scientific Communication and Support Yamina and Badr discussed the need for a well-organized lab manager to facilitate communication within their global scientific team and ensure scientists could focus on their research. They identified the challenges scientists, particularly students and researchers, face, such as imposter syndrome, constant pressure from administrative tasks, and difficulties in maintaining a work-life balance. Yamina and Badr agreed on the importance of individuals struggling with imposter syndrome learning to set aside their fears and doubts to move forward. They also highlighted the benefits of maintaining a supportive network and engaging in non-lab activities for mental processing and relaxation. Academia and Industry Strategies Discussed Yamina and Badr discussed the challenges and strategies of a scientist in academia and industry. Yamina highlighted the need to project a certain presence and balance one’s actions against others in the field. She also mentioned the importance of careful communication, especially when working with a boss who has a different approach. Badr agreed to reach out for a future collaboration, and they discussed the possibility of meeting in Boston. Yamina committed to sending her contact details to Badr. Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

Hay on class B GPCRs, RAMPs, and the selectivity problem in CGRP-targeted migraine therapies - what the approved drugs may still be getting wrong. << Back to podcast list Strategic Partner(s) Debbie Hay: Class B GPCRs, RAMPs, and the Migraine Pharmacology Gap Class B GPCRs represent one of the smaller subfamilies in the GPCR superfamily - just 15 receptor genes - yet they govern a disproportionately wide range of physiology, from calcitonin-mediated bone remodeling to the peptide signaling networks underlying migraine. Their pharmacological complexity is amplified by receptor activity modifying proteins (RAMPs), three single-pass membrane proteins that associate with these receptors to create pharmacologically distinct complexes. A single receptor can form three different functional units depending on which RAMP is present, and those distinctions determine ligand selectivity, signaling output, and ultimately drug targeting. Hay examines the molecular pharmacology of the calcitonin receptor and calcitonin-like receptor - with particular focus on their RAMP-dependent behavior and their roles in CGRP-mediated migraine. She argues that the field has moved faster than the evidence warrants: approving antibodies and small molecules against receptor targets whose full selectivity profile remains uncharacterized. For Hay, who has studied RAMPs since they were first described and when working on them was a high-risk research bet, the CGRP drug approvals are both a vindication and a reminder of how much foundational pharmacology the field skipped on the way to the clinic. ABOUT THE GUEST Hay is a professor of pharmacology at the University of Otago, New Zealand. Her research centers on the molecular pharmacology of class B GPCRs - specifically the calcitonin receptor and calcitonin-like receptor - and their interactions with RAMPs. She has worked across pharmaceutical, biotechnology, and academic settings, including a research placement at GlaxoWellcome, a PhD in molecular pharmacology at Imperial College London, and 17 years at the University of Auckland, where she led her own laboratory and served as head of department. Her current work addresses one of the central unsolved problems in RAMP pharmacology: developing tools selective enough to distinguish between closely related receptor-RAMP complexes in disease-relevant tissues. SCIENTIFIC THEMES OF THE CONVERSATION RAMP-dependent pharmacological diversity in class B GPCRs The selectivity problem in CGRP-targeted migraine therapies Obligatory receptor heterodimers and the limits of current characterization tools Structural biology of RAMPs - allosteric modulation over direct ligand contact Reproducibility and target validation as prerequisites for meaningful GPCR pharmacology Career navigation across academia, big pharma, and biotech KEY INSIGHTS FROM THE CONVERSATION Fifteen Genes, Far More Than Fifteen Pharmacologies Class B GPCRs are a small family by gene count, but RAMP association multiplies their pharmacological diversity considerably. Each of the three RAMPs can pair with a given receptor to produce a distinct complex - different ligand selectivity, different signaling profile, different therapeutic implications. The field routinely treats these complexes as interchangeable, but Hay argues they are not, and that assumption has downstream consequences for how drugs are characterized and how trial failures are interpreted. The Erenumab Selectivity Problem Erenumab, the first monoclonal antibody approved against a GPCR complex, targets the CLR-RAMP1 receptor - the canonical CGRP receptor in migraine. But Hay makes the case that the antibody's selectivity for this complex over the closely related CTR-RAMP1 complex has never been adequately demonstrated. Shared structural features between the two receptor complexes, combined with the known pharmacology of CGRP at CTR-RAMP1, suggest the drug may be less target-selective than its approval label implies - and that effects attributed to one target may partly involve another. mRNA Cannot Tell You Where the Functional Dimer Is For obligatory heterodimers like RAMP-receptor complexes, knowing which component genes are expressed in a cell tells you surprisingly little. The functional unit is the assembled complex at the cell surface, and that assembly is not predictable from transcript data - even at single-cell resolution. Hay frames this as one of the foundational unsolved problems in RAMP pharmacology: without tools to visualize and quantify the actual complex in native tissue under disease conditions, target validation remains incomplete and the pharmacology remains unresolved. RAMPs Act Allosterically - Not Through Direct Ligand Contact Structural data from the CLR and CTR receptor families has produced a result that surprised the field: RAMPs contribute almost no direct molecular contacts to the bound ligand. Their influence on receptor pharmacology appears to be primarily allosteric - subtly reshaping the GPCR binding site rather than contributing their own contact surface. This reframes the design challenge for RAMP-selective compounds: the differences between receptor complexes are conformational and fine-grained, not structurally obvious, making ligand selectivity considerably harder to engineer than a direct-contact model would predict. The Migraine Pharmacology Gap CGRP is elevated in migraine, infused CGRP triggers migraine-like headache in susceptible individuals, and drugs targeting that pathway can abolish chronic migraine entirely for some patients - while doing nothing for others. The mechanistic story remains incomplete: which receptor complex mediates which symptom, why the response is so variable across patients, and what the CGRP system is actually doing in the peripheral and central nervous system. For a condition affecting up to 20% of women worldwide, Hay notes, the research investment in understanding the receptor-level biology is strikingly insufficient. Burning Curiosity as the Non-Negotiable Hay's advice to junior scientists distills to a single criterion: if the curiosity isn't deep enough to outlast the failures, the career won't hold. Grant rejections, papers rejected seven times, experiments that don't replicate - these are not exceptional events but structural features of a scientific life. The scientists who persist, in her framing, are not the ones who feel less pain from those setbacks, but the ones for whom the pull toward the question is stronger than the push of the failure. She gives herself one day to be unhappy about a rejection. Then she moves on. EPISODE TIMELINE Timestamps are AI-generated from the episode transcript and are approximate. Minor offsets may occur in the final edited episode. 00:00 Welcome and episode announcements 01:40 Introduction - Hay 02:43 Career trajectory - from vet school to GPCR pharmacology 07:55 First encounter with GPCRs at GlaxoWellcome - and how RAMPs entered the picture 11:03 Class B GPCRs - why 15 receptor genes produce far greater pharmacological diversity than expected 13:30 CGRP, migraine, and the first antibody approved against a GPCR complex 18:50 Migraine as an invisible disability and the limits of what current treatments explain 20:41 Obligatory dimers and the challenge of mapping receptor complexes in disease-relevant tissue 23:54 Tools the field needs - antibody selectivity, selective ligands, and bimolecular fluorescence complementation in vivo 26:42 Structural data and what it reveals about how RAMPs actually modulate receptor pharmacology 29:43 Are GPCRs still good drug targets - and what is missing from class B pharmacology 31:41 Reproducibility, target validation, and the cost of science that cannot be repeated 34:53 Career advice - burning curiosity, celebrating wins, and being kind SELECTED QUOTES "I can't pick a favorite because these are such complex receptors and we fundamentally don't understand which are most important. Because we don't have selective ligands." "We have to know where our receptor is in our tissue of interest, in our disease condition, and how it is signaling - because that is what we need to target." "There is too much out there that is not replicable. And it causes careers to die. It's just not fair on the junior scientists who then follow up on that work to find it can't be repeated." "If you've got that deep, deep drive still to get over those failures and pick yourself up, and that's a strong enough fire burning, then you will succeed." About this episode Dr. Debbie Hay is presently a professor at the Department of Pharmacology and Toxicology at the University of Otago after spending 18 years at the University of Auckland. Her work is primarily focused on class B GPCRs and their interactions with RAMPs. Debbie obtained a Ph.D. in Molecular Pharmacology from Imperial College London in the UK. She has gained experience from working in academia and at GSK as an industrial trainee. Join me and learn more about Debbie’s career and what she learned through her experiences as a scientist. Dr. Debbie Hay on the web LinkedIn Wikipedia University of Otago University of Auckland Google Scholar Pubmed Research Gate Twitter Dr. GPCR Ecosystem Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Dr. Caron Tribute Part 2 About Marc Caron Dr. Caron and his family moved to Durham, NC in 1977, following receipt of his BSc in Chemistry from Laval University and his Ph.D. from the University of Miami. He joined the faculty of Laval University School of Medicine in 1975 and then returned to join Duke’s faculty, where he remained as a James B. Duke Professor until his death. He and his laboratory members studied the mechanisms of action and regulation of hormones and neurotransmitters and how they might underlie brain and behavior disorders such as schizophrenia, Parkinson's disease, attention-deficit hyperactivity disorder, mood disorders, and addiction. Among his many honors, Dr. Caron was an investigator of the Howard Hughes Medical Institute from 1992 to 2004, a member of the American Academy of Arts & Sciences, a fellow of the American Association for the Advancement of Science, and a recipient of the Julius Axelrod Award. An authoritative and prolific scientist, with over 650 scientific publications, he is most beloved as a mentor and his relentless encouragement that shaped the careers of hundreds of scientists worldwide. About our panelists in alphabetical order and the year they first met Dr. Caron Dr. Larry Barak (1994) Dr. Kathleen Caron - Co-host- (1970) Dr. Steve Ferguson (1995) Dr. Neel Freedman (1994) Dr. Jacob Jacobson (2003) Dr. Stephane Laporte (1999) Dr. Stuart Maudsley (1997) Dr. Richard Premont (1993) Dr. Jie Zhang (1990) Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Dr. Robert F. Bruns About Dr. Robert F. Bruns Fred Bruns discovered the first positive allosteric modulator (PAM) of a GPCR in the late 1980s while working at Warner-Lambert/Parke-Davis. The work was published in 1990. After 7 years at WL/PD and 26 years at Eli Lilly & Co., he retired at the end of 2014 and since then has been writing papers on his final major project at Lilly, a dopamine D1 PAM series that has advanced through Phase 2 clinical trials. Fred obtained an A.B. in Psychology from Washington University in St. Louis, followed by a Ph.D. in Neurosciences at the University of California, San Diego. His doctoral dissertation was the first large-scale study of structure-activity relationships for adenosine receptors. During a joint postdoc with John W Daly at NIH and Solomon Snyder at Johns Hopkins, he developed the first adenosine receptor binding assay. He then joined WL/PD, where his lab demonstrated the existence of two subtypes of the adenosine A2 receptor, A2a and A2b. In 1988, he joined Lilly as a receptor biologist in charge of a high-throughput screening lab. He taught himself chemoinformatics as a way to optimize compound selection for screening, and in 1997 switched to computational chemistry full-time. He supported the D1 PAM project in various roles from its inception in 2002 until selection of a clinical candidate in 2013. Dr. Bruns has over 80 publications and 11,000 citations, with an h-index of 47. Dr. Robert F. Bruns on the web ResearchGate LinkedIn Dr. GPCR Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

Chris Tate co-founded Heptares after reading one paper on a Friday afternoon. This conversation covers thermostabilization, cryoEM, and GPCR structural biology. << Back to podcast list Strategic Partner(s) Chris Tate: Thermostabilizing GPCRs for Structural Biology For most of the 1990s and early 2000s, GPCR structural biology was not a biology problem - it was a stability problem. Receptors that fell apart in any useful detergent could not be crystallized, and without crystals, there were no structures. Chris Tate spent years working on membrane proteins that were simply too unstable to study by crystallography, and the question of how to solve that became the organizing problem of his career. The answer came from an unexpected source: a paper on thermostabilization of an unrelated membrane protein, read on a Friday afternoon in the library. That insight led to a systematic mutation screen, a 21-degree improvement in receptor thermostability, and eventually the co-founding of Heptares - a company now running over 250 GPCR structures and six clinical candidates. This conversation covers how thermostabilization changed what was structurally possible, how cryoEM then redrew the map again, and what the first solved Class D GPCR dimer reveals about receptor architecture at its most unexpected. ABOUT THE GUEST Chris Tate is a group leader at the MRC Laboratory of Molecular Biology in Cambridge, UK, where his research focuses on the structural and biochemical study of membrane proteins, with particular emphasis on GPCRs. His work developed the thermostabilization platform - a systematic approach to engineering receptor stability for structural biology - that enabled the first high-resolution crystal structures of multiple GPCRs in defined conformational states. He co-founded Heptares (now Sosei Heptares) in 2007, a company that has since produced over 250 GPCR structures and advanced six candidates into clinical trials. His current structural work extends to Class D GPCRs, including the recently solved first dimer architecture in this receptor family. SCIENTIFIC THEMES OF THE CONVERSATION Membrane protein instability as the overlooked bottleneck in GPCR structural biology The thermostabilization platform - from concept to systematic mutation screen From academic discovery to co-founding Heptares: decision, funding, and growth CryoEM and the conformational states that crystallography could never access Class D GPCR architecture - what a dimer with no prior blueprint looks like What remains unsolved: why drug discovery still fails in late-stage clinical trials KEY INSIGHTS FROM THE CONVERSATION Stability, not biology, was the bottleneck The reason GPCR structures took so long was not scientific complexity - it was that the receptors destroyed themselves in every detergent needed for crystallography. Tate's work reframed the problem: before asking what a receptor does, you first have to ask whether it can survive the conditions required to study it. A Friday afternoon and a paper on an unrelated protein The thermostabilization insight did not come from the lab. It came from Tate's habit of spending Friday afternoons in the library reading outside his immediate field. A 1999 paper on thermostability of diacylglycerol kinase - a protein with no connection to GPCRs - produced a light-bulb recognition that reshaped his entire research direction. 21 degrees changed what was chemically possible Thermostabilizing the beta-adrenergic receptor by 21 degrees Celsius was not a marginal improvement. It meant the receptor could survive in harsh short-chain detergents that had previously killed it instantly - including SDS. That stability was what made crystallization tractable and what became the foundation of Heptares. CryoEM opened conformational space that crystallography had locked out The arrestin-coupled state of a GPCR - a structure that required the agonist-bound receptor to be held in its active conformation - could never have come from crystallography. CryoEM removed that constraint, and Tate argues the field is still at the beginning of what this means: inactive-state structures, full conformational sets, and throughputs that were previously inconceivable. A Class D GPCR dimer with no prior blueprint The first solved structure of a Class D GPCR - a yeast receptor from family D - turned out to be a dimer, with an architecture that breaks the rules of class A receptor biology. The dimer interface sits on helix 1, involves a domain-swapped N-terminus and helix 7, is twice the area of the G protein coupling interface, and positions helix 4 over 20 angstroms from where it appears in any known class A receptor. A PhD student solved it in under two years. Drug discovery's real bottleneck is not structural Tate is direct about where the field now stands: accumulating GPCR structures is no longer the limiting step in drug discovery. The harder problem is understanding the human body well enough to predict why a compound that works in vitro fails in Phase 2 or Phase 3 - and solving that will require tools and systems that structural biology alone cannot provide. Science requires a skin like a rhino Tate's advice to young scientists is not procedural - it is temperamental. Science is brutal, things fail for months, and the only way through is genuine passion for being in the lab. He still asks every candidate who wants to join his group one question: do you know, in chemical terms, how a miniprep kit works? The answer reveals whether someone is curious about science or merely using it. EPISODE TIMELINE Timestamps are AI-generated from the transcript and may vary slightly from the final edited audio. 01:35 Meet Tate - membrane protein biochemist, MRC LMB 02:12 Career origin: from calcium ATPase to bacterial transporters 13:52 Path into GPCRs - instability as the bottleneck nobody was solving 17:00 The Friday afternoon library paper that changed GPCR structural biology 24:21 Thermostabilizing the beta receptor by 21 degrees - in any detergent, including SDS 25:56 Co-founding Heptares - the canteen conversation and the venture capital meeting 32:02 Raising £21M during the 2009 financial crisis 37:43 The cryoEM revolution - why the arrestin-coupled structure could never have come from a crystal 45:17 Unpublished: a Class D GPCR dimer - one PhD student, 18 months, a Nature paper 49:05 Advice for young scientists: what it actually takes to survive science 54:35 The curiosity test: do you know how your miniprep kit works? 58:34 Three aha moments - a diffraction pattern, a thermostabilization screen, and a synchrotron SELECTED QUOTES "None of my best ideas have ever arisen from being in the lab. Never. Because when you're in the lab, you're thinking about what's in front of you." "I don't think ever in my life I will ever write an application and just produce so much more than what I wrote in the original application." "Science is brutal. It is absolutely brutal. Things don't work for months. You have to be robust, you have to have a skin like a rhino sometimes." "When you see the GPCR field, all you see is this accelerating number of structures and information, and that is just going to get faster and faster. And I think that is now the minor part." About this episode Dr. Chris Tate obtained his Ph.D. from the University of Bristol in 1989 and then moved to the University of Cambridge (Dept. of Biochemistry) to work on bacterial sugar transporters. After obtaining a research fellowship at Girton College (Cambridge) he moved to the LMB in 1992 to work in Richard Henderson's group on the serotonin transporter. Chris also worked on the E. coli multidrug transporter EmrE and obtained both 2D and 3D crystals as well as a 3D structure using cryo-EM. In 2005 he started working on the development of conformational thermostabilization of GPCRs, which resulted in the structure of the β1-adrenoceptor. Subsequent work has focused on understanding the molecular basis of GPCR pharmacology through structure determination of the β1-adrenoceptor and adenosine A2A receptor in multiple different conformations bound to ligands of different efficacy. In 2016 mini-G proteins were developed as a tool for the structure determination of GPCRs in the fully active state. Structures have been determined by X-ray crystallography of receptors coupled to either mini-Gs or mini-Go, and also by electron cryo-microscopy of receptors coupled to mini G protein bound to βγ subunits. Recent work includes the first structure determination of a GPCR bound to a biased agonist and coupled to arrestin and also the first structure of a Class D receptor. Join me to learn more about Chris’s work and his role in founding Heptares which was later acquired by Sosei and became Sosei Heptares . Dr. Chris Tate on the web LinkedIn ResearchGate Pubmed Google Scholar Sosei Heptares Wikipedia MRC Laboratory of Molecular Biology Dr. GPCR Ecosystem Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. 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<< Back to podcast list Strategic Partner(s) Dr. Benjamin Myers About Dr. Benjamin Myers Ben Myers is an assistant professor at the University of Utah School of Medicine in Salt Lake City, UT, and an investigator with the Huntsman Cancer Institute. Ben’s research focuses on Smoothened and other class F GPCRs which play essential roles in embryonic development and in cancer. His group studies the unusual signaling mechanisms employed by these atypical 7-transmembrane receptors, combining biochemical and structural approaches with cell biology and in vivo models. These studies have revealed new and unexpected ways for membrane lipids to regulate GPCR activity and for GPCRs to control intracellular kinases. More recently, Ben’s lab has begun studying GPCR signaling pathways that operate within the primary cilium, a tiny antenna-shaped structure at the cell surface with critical links to development, physiology, and disease. Ben studied developmental and cancer signaling as a postdoctoral fellow with Philip Beachy at Stanford University. Prior to that, Ben received his Ph.D. from UCSF in 2008, where he worked with David Julius on the structure, function, and physiology of ion channels and GPCRs in the nervous system. Dr. Benjamin Myers on the web Website Twitter Pubmed University of Utah Dr. GPCR Ecosystem Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Dr. Pierre Eftekhari About Dr. Pierre Eftekhari "Clinical physiologist and biologist , with more than 25 years of experience in drug development. have been engaged in GPCR cellular and clinical pharmacology as scientist or PI in neonatal lupus, Cardiomyopathy, hypertension, chagas disease. I have participated and initiated methodologies for development of pharmacologically active anti-GPCR antibodies like agonist, antagonist, inverse agonist or blocker. During my Scholar period I have published or contributed in 38 published scientific work mainly in the field of immunology and pharmacology of GPCR. The majority of my research is concentrated on rhodopsin family with a few works on metabotropic receptor. Since the creation of Inoviem scientific in Nov. 2011 by myself we have been regularly working with GPCRs for our pharma and biotech clients. The latter mainly in target deconvolution and patient stratification." Dr. Pierre Eftekhari on the web Inoviem Scientific ResearchGate LinkedIn Twitter Dr. GPCR Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

Elva Zhao on biased agonism at the GLP-1 receptor, G protein regulation, and building a mechanistic picture of GPCR pharmacology from the inside out. << Back to podcast list Strategic Partner(s) Elva Zhao: G Protein Regulation and Biased Signaling at the GLP-1 Receptor The GLP-1 receptor is among the most clinically validated targets in metabolic disease - yet the signaling logic separating the therapeutic benefit of existing drugs from their adverse effects remains poorly resolved. At the center of that problem is biased agonism: the differential engagement of downstream pathways by distinct ligands acting at the same receptor. Understanding which transducer coupling events produce glucose-lowering efficacy and which drive the GI side effects that limit GLP-1 agonist use demands a mechanistic account of receptor-G protein engagement and its regulation. Elva Zhao brings an unusual vantage point to that question. Her PhD at Western University focused not on receptors but on G protein cycle regulation - RGS proteins, GoLoco proteins, and the kinetics of GTP binding and hydrolysis. That training, initially set aside during postdoctoral work on biased agonism at Monash, is now being reintegrated deliberately. Her current research asks how the regulatory proteins that most GPCR pharmacologists have not yet addressed actually shape signaling output at one of the field's most important therapeutic targets. The connection runs deeper than science: Zhao's grandmother worked as a pharmacologist on diabetes in China - decades before her granddaughter would begin studying the receptor that now defines modern diabetes pharmacotherapy. About the Guest Elva Zhao is a Research Fellow at the Monash Institute of Pharmaceutical Sciences (MIPS), Drug Discovery Biology, in Melbourne, Australia. She completed her PhD at Western University, Canada, under Prof. Peter Chidiac, where her work focused on the kinetic regulation of G protein cycling by RGS proteins and GoLoco motif-containing proteins. She subsequently joined MIPS for postdoctoral training, working first with Prof. Nigel Bennett on biased signaling at the PAR2 receptor, then with Profs. Denise Wootten and Patrick Sexton on class B GPCR pharmacology and biased agonism at the GLP-1 receptor. Her current research integrates both frameworks - examining how the GLP-1 receptor engages its transducer partners and how G protein regulatory proteins shape downstream signaling in a physiological context. Scientific Themes of the Conversation G protein cycle regulation and the kinetic roles of RGS and GoLoco proteins Biased agonism at class B GPCRs - ligand-dependent pathway selectivity at the GLP-1 receptor Transducer coupling as the missing mechanistic layer in GLP-1 receptor pharmacology The expanding therapeutic profile of the GLP-1 receptor - from diabetes and obesity to neurodegeneration How collaborative, GPCR-focused research environments change what questions are askable Scientific identity across discontinuous environments - building a research program across three countries and multiple pharmacological frameworks Key Insights from the Conversation 1. The G Protein Regulatory Layer GLP-1 Research Has Not Yet Addressed The pharmacological characterization of GLP-1 receptor agonists has concentrated on receptor-level biased signaling - which downstream pathways are activated - while the proteins that regulate G protein cycle kinetics have received almost no attention in this context. Zhao's research begins to ask what RGS proteins and GoLoco proteins do to modulate the functional output at this receptor, and whether that regulatory layer contributes to the therapeutic window problem that GLP-1 drug development has not solved. 2. Why GLP-1 Drugs Still Produce Nausea - and What Biased Signaling Might Fix The GI side effects of GLP-1 receptor agonists - primarily nausea and vomiting - remain among the main barriers to broader clinical use and optimal dosing. Zhao describes how the objective of biased agonism research at the GLP-1 receptor is to develop ligand profiles that preserve glucose-lowering efficacy while decoupling the pathways driving adverse effects. Executing that requires knowing, with mechanistic precision, which coupling events map to which clinical outcomes. 3. The Scientific Circle Nobody Plans For Zhao's PhD - focused entirely on G protein regulation without studying a receptor - appeared to be a separate chapter from her postdoctoral work on receptor pharmacology and biased agonism. A decade later, she is deliberately bringing both ends of that arc together. The insight that G protein regulatory proteins may shape the functional selectivity of GLP-1 agonists in a physiological context is not a planned convergence - it is the result of building two skill sets sequentially and eventually recognizing that neither was complete without the other. 4. GLP-1 Receptor as a Window Into Neurodegeneration Beyond its established roles in glucose homeostasis and body weight regulation, emerging evidence points to a role for GLP-1 receptor signaling in Parkinson's disease and Alzheimer's disease. Zhao describes how this expanding target profile changes the stakes of understanding how the receptor works - not only in pancreatic beta cells and the periphery, but in neural tissue, where the downstream consequences of biased coupling may differ substantially. 5. What a GPCR-Only Environment Makes Possible The move from a broad pharmacology department in Canada to the GPCR-focused, shared-space environment at MIPS was scientifically consequential for Zhao. Working alongside structural biologists, computational pharmacologists, and receptor scientists working across GPCR classes gave her the methodological range to ask questions she could not have formulated in a more siloed setting - and access to expertise she could find simply by walking to the right floor with a laptop. 6. Following the Question, Not the Credential Zhao describes her decision to pursue a postdoc as emerging from a straightforward observation: there was still a question she wanted to answer. Her mentor, Peter Chidiac, had consistently avoided steering her toward a predetermined career path, asking instead which question she most wanted to work on. That framing - orienting around the scientific problem rather than the next credential - organized each subsequent move she made, from Western to Monash, and from G proteins to receptors and back again. 7. The International Student Trap - Nodding Yes When You Don't Understand One of the frankest passages in the conversation concerns the habit of nodding along when a supervisor is speaking and nothing has been understood - a pattern Zhao describes as nearly universal among international PhD students. The forces behind it are layered: language barriers, cultural conditioning around deference, the general insecurity of early-stage training, and the fear of appearing incompetent. The correction, for Zhao, came slowly - driven by a mentor patient enough to make asking safe, and by the unavoidable evidence that unacknowledged confusion produces problems on both sides of the relationship. Episode Timeline Timestamps are AI-generated from the transcript and are approximate. Minor offsets may occur. 00:00 Introduction and Dr. GPCR Virtual Cafe announcement 01:49 Zhao's scientific background - from Shanghai to Western University 06:49 First contact with G proteins - the muscarinic receptor as a tool, not a subject 09:17 From China to Canada - the international student experience and the language gap 15:09 The mentor who made it safe to say "I don't understand" 19:38 Why Australia - how a single conference in Melbourne redirected the next chapter 22:28 The decision to pursue a postdoc - following the question before you hate the science 28:46 Life at MIPS - collaborative, GPCR-focused, and unexpectedly open 32:30 From PAR2 to GLP-1 - building the mechanistic picture one step at a time 37:01 GLP-1 receptor biology - diabetes, obesity, and the emerging neurodegenerative angle 38:50 Why GLP-1 drugs still need improvement - the side effect problem 41:39 Work-life balance - running, Tilly, and what burnout taught about efficiency 52:58 COVID as unexpected space to think, organize data, and build collaborations 57:58 Advice for trainees - staying curious, knowing your question, and talking to people Selected Quotes "I want to know more of how it's regulated, but I want to know more of upstream. I want to know how the G protein got activated. So receptor is a natural choice." "I feel like I'm not finished yet with answering my own question. And also, I'm fresh out of PhD. I don't hate science yet. So why not do a little bit more?" "On the good day - relatively okay day - I always remind myself of the not so good days, thinking that, okay, I've been there but I'm here now, so I can do this thing." "Keep the core to what is the question that you want to answer. Don't try to be distracted by needing a big paper. Always just keep the core." About this episode Elva is currently a research fellow at the Monash Institute of Pharmaceutical Sciences. Elva moved to Canada where she obtained her Ph.D. at the University of Western Ontario, working on the regulation of G proteins signaling by accessory proteins, such as RGS proteins and GPSM proteins. After her Ph.D., she moved to Australia and continues working on GPCRs. Her current research focuses on class B GPCRs and understanding how GPCR signaling and function is mediated by various ligands, binding partners, and intracellular machinery. In her spare time, Elva likes to run in the mountains, play with Tilly (a 9-year old retired greyhound), collecting mini shoes, and hang out with friends. Join me to learn more about Elva, class B GPCRs, and Tilly. Dr. Elva Zhao on the web LinkedIn Monash University Pubmed Twitter Dr. GPCR Ecosystem Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. 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<< Back to podcast list Strategic Partner(s) Dr. Simone Prömel & Dr. Ines Liebscher About Dr. Simone Prömel Simone Prömel is currently a professor of cell biology at the Heinrich Heine University Düsseldorf, Germany. Being a biochemist by training, she completed her Ph.D. at the Institute of Biochemistry at the University of Oxford, UK. During this time, she discovered her love for Adhesion GPCRs and started delineating the molecular mechanisms of the Adhesion GPCR Latrophilin-1. These extraordinary receptors, about which there was not much known other than that they are huge and somehow play important roles in health and disease, fascinated her so much that she continued working on them when she started her own lab at Leipzig University. There she focused on the different modes of action of Adhesion GPCRs and found that they do not only mediate classical G protein signals into cells but can also communicate solely via their N termini. Today, she and her team are working on the questions of how Adhesion GPCRs integrate the different signals on a molecular level and how these are translated into physiological functions in various model organisms. Together with Ines Liebscher, Simone is leading an EU-funded COST Network on Adhesion GPCRs: CA18240 Adher´n Rise. Dr. Simone Prömel on the web Prömel Lab Pubmed Researchgate Twitter Dr. GPCR Ecosystem About Dr. Ines Liebscher Dr. Liebscher is a Professor at the Rudolf Schönheimer Institute of Biochemistry at the Medical Faculty of the Leipzig University. During her medical studies in Leipzig, she had her first encounter with an orphan GPCR as the subject of her MD thesis. Being faced with the vast unknown biochemical and pharmacological territory that would be helpful to study orphan receptors she enrolled in the MD/Ph.D. program of Leipzig University. Her postdoctoral work leads her to investigate a whole family of orphan receptors: adhesion GPCRs. With the little knowledge on these receptors available, there were multiple questions to tackle. Starting with proving and characterizing G-protein coupling, Ines spends several years studying the activation mechanism of adhesion GPCRs. In collaboration with great fellow adhesion GPCR scientists around the globe she established a tethered agonist -extracellular matrix- mechano-activation- activation scenario that forms the basis for her current projects that focus on the structural and physiological implications of these findings. Together with Simone Prömel, Ines is leading a COST Network on adhesion GPCRs: CA18240 Adher'nRise. Dr. Ines Liebscher on the web Website LinkedIn Researchgate Dr. GPCR Ecosystem Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Dr. Adriano Marchese About Dr. Adriano Marchese Adriano Marchese is a Professor of Biochemistry at the Medical College of Wisconsin. Adriano received his Bachelor of Science degree in Pharmacology in 1991 from the University of Toronto. He continued his graduate studies at the University of Toronto where he earned his MSc (1994) and Ph.D. (1998) in Pharmacology. He then moved to Thomas Jefferson University in Philadelphia, PA, for his postdoctoral training in Jeff Benovic’s laboratory studying the regulation of G protein-coupled receptor trafficking and signaling. In 2004 Adriano joined the faculty of the Department of Pharmacology at Loyola University Chicago. In 2016 he decided to move his lab to the Medical College of Wisconsin in Milwaukee, WI. Adriano’s research has contributed to our understanding of the role that ubiquitin plays in GPCR signaling and trafficking. His laboratory is interested in understanding the mechanisms that govern spatial and temporal regulation of GPCR signaling by -arrestins and post-translational modifications (PTMs), such as phosphorylation, ubiquitination, and SUMOylation. His lab has shown a role for -arrestins and PTMs in GPCR trafficking and signaling and has leveraged this knowledge to reveal the spatial and temporal requirements for GPCR activation of signaling pathways related to cell survival, proliferation, and migration. The ultimate goal of Adriano’s research is to target novel aspects of GPCR signaling for therapeutic development. Dr. Adriano Marchese on the web Twitter LinkedIn Google Scholar Website Dr. GPCR Ecosystem Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Dr. Jean Martin Beaulieu About Dr. Jean Martin Beaulieu Dr. Beaulieu received a Ph.D. in Neurological Sciences from McGill University and completed his post-doctoral training at Duke University. Prior to his recruitment Dr. Beaulieu was an associate professor and Canada Research Chair (Tier2) in the Department of Psychiatry and Neuroscience at Laval University. Dr. Beaulieu’s research is aimed at understanding how cellular and molecular mechanisms regulated by psychoactive drugs intersect with genetic risk factors for mental illnesses such as schizophrenia, depression, and bipolar disorder. Dr. Beaulieu has pioneered work establishing a role for Beta-arrestin signaling in the brain in vivo and has established its importance in D2 dopamine receptors (D2R) functions. These receptors belong to the super-family of G-protein coupled receptors (GPCR), the major molecular target for drug development. In particular, D2R is the main pharmacological target of antipsychotic drugs prescribed for schizophrenia and bipolar disorders. Work by the Beaulieu Lab has demonstrated that mood stabilizer drugs (e.g. lithium) used for bipolar disorder therapy target signaling mechanisms regulated by dopamine receptors, thus providing a framework to understand how different drug classes can engage overlapping cellular mechanisms to exert their action. The Beaulieu group is presently investigating how cell surface express proteins can act as allosteric modulators of D2R signaling and explores the potential usefulness of beta-arrestins for the development of new pharmaceutical agents. Translational validation is important to validate findings obtained from experimental models research and bridge the gap between bench and bedside. Working in collaboration with geneticists, the Beaulieu-Lab has identified interactions between cellular mechanisms engaged by D2R and psychiatric drugs with genetic risk factors implicated in schizophrenia by large whole-genome association studies (GWAS) in humans. These investigations have led to the identification of an RNA binding protein (FXR1P) involved in the regulation of protein synthesis as a potential downstream effector of the action of mood stabilizers and other psychoactive drugs. In addition to basic research, the Beaulieu group is also actively implicated in translational research and industry collaboration to develop new drugs and drug development technology. Dr. Jean Martin Beaulieu on the web University of Toronto Google Scholar LinkedIn ResearchGate Dr. GPCR Ecosystem Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

From chemokine receptors at Rockefeller to founding Dr. GPCR during COVID — the career arc behind the ecosystem built for the field's unreached receptors. << Back to podcast list Strategic Partner(s) Yamina Berchiche: Beyond the Lab — From Chemokine Receptors to the Dr. GPCR Ecosystem Dr. Yamina Berchiche spent two decades working on G protein-coupled receptors at the bench — training that spanned chemokine receptor conformational dynamics at the Université de Montréal, CXCR3 splice-variant signaling at Rockefeller University in Dr. Tom Sakmar's lab, CRISPR knockout generation at NIAID, and class B peptide receptor work at Generate Biomedicines. Across those stops, one observation kept resurfacing: the GPCR field is enormous — roughly 400 non-olfactory receptors — but clinical drug discovery has reached only about 166 of them, leaving more than 250 receptors unstudied at anything close to therapeutic depth. This conversation traces the scientific arc that led Dr. Berchiche to leave the bench after a COVID-era redundancy, and examines the motivation behind founding Dr. GPCR — an ecosystem of podcasts, newsletters, summits, and working spaces designed to give the field connective tissue it has historically lacked. For Dr. Berchiche, this work is personal: the receptors she helped characterize for years belong to a family she believes has been collectively underserved by the infrastructure around it, and building that infrastructure has become a full-time scientific question in its own right. About the Guest Dr. Yamina Berchiche is the founder of the Dr. GPCR ecosystem and the host of the Dr. GPCR Podcast. She holds a PhD in Biochemistry from the Université de Montréal, where she trained in Dr. Nikolaus Heveker's lab at the CHU Sainte-Justine Research Center on chemokine receptor structure–function relationships, with extensive collaborative work in Dr. Michel Bouvier's lab on BRET-based conformational readouts. She completed postdoctoral training at Rockefeller University in Dr. Tom Sakmar's lab, where she characterized the signaling diversity of three alternative splice variants of CXCR3. Her career has moved through academic pharmacology, a research fellowship in B-cell molecular immunology at NIAID, and a senior scientist role at Generate Biomedicines, where she worked on class B peptide receptor engineering using AI-driven protein design. She now builds scientific community infrastructure for the GPCR field. Scientific Themes of the Conversation Chemokine receptor redundancy and the shift toward functional selectivity as a framework Splice variants as signaling variants — CXCR3 as a case study for transcript-level diversity The orphan-majority problem in GPCR drug discovery — why ~250 non-olfactory receptors remain outside clinical attention Career architecture for bench pharmacologists moving beyond academia and biotech Scientific community as infrastructure — what connective tissue a 400-receptor field actually needs Assay design as the lever that shifts conceptual frameworks Key Insights from the Conversation Rejection as redirection. The summer placement Dr. Berchiche didn't get in Michel Bouvier's lab led her to Nikolaus Heveker's newly opened lab at CHU Sainte-Justine, where she was the first student. The lab had no equipment, only stacks of bills on every bench — and a research program on chemokines and chemokine receptors that would define her career. The redundancy assumption crumbled under better assays. The chemokine system — roughly 50 ligands for 20 receptors — was framed for decades as redundant because multiple chemokines bind multiple receptors. Dr. Berchiche's thesis work on CXCR4 mutants and her PhD characterization of natural chemokines binding CCR2B showed the opposite: distinct ligands activate distinct signaling outputs, and functional selectivity was quietly hiding inside what had been called promiscuity. Splice variants aren't just structural — they signal differently. Her Rockefeller work on the three alternative splice variants of CXCR3, initially prompted by a simple question from Tom Sakmar, demonstrated that variants encoded by the same gene can recruit different signaling outputs in response to the same ligands. The implication: transcript-level diversity is itself a signaling mechanism, not a cloning artifact to be collapsed away. The 250-receptor problem sits in plain sight. Of roughly 400 non-olfactory GPCRs, only about 166 are being targeted or studied for clinical application. The remaining 250+ are not obscure — they are simply not connected to drug-discovery momentum. This gap, visible in the 2017 mapping work by Dr. Alexander Hauser and colleagues, is the motivating tension behind Dr. GPCR. The 30,000-foot view requires leaving the bench. After nearly two decades in the lab, Dr. Berchiche found that deep focus on one project was no longer fulfilling. The bench scientist's perspective — which she explicitly values — comes at the cost of the field-level view that ecosystem-building requires, and choosing between them turned out to be a real career architecture decision rather than a detour. Community is scientific infrastructure, not marketing. A podcast, a monthly newsletter, and a virtual summit are not promotional surfaces. They are the connective tissue a 400-receptor field uses to exchange techniques, ideas, and trust across institutional boundaries. Without that tissue, GPCRs stay siloed by receptor family and by lab. Building during a pandemic is a design constraint, not a footnote. Dr. GPCR was founded in March 2020 after a COVID-era redundancy at Generate Biomedicines. Early episodes were recorded in a Toyota Prius parked outside a gym with public Wi-Fi, and then in a closet studio her husband built so she could keep the AC running without bleeding background noise into the audio. The ecosystem's physical origins are inseparable from its founding conviction. Episode Timeline Timestamps were generated using AI for readability. 00:00 Introduction 02:25 The closet studio and what's in the talk 04:00 From Oradea to Montreal — the geography of a GPCR career 06:30 An empty lab and the chemokine redundancy problem 09:00 A master's, old-school molecular biology, and an accelerated JBC paper 11:00 CCR2B, functional selectivity, and a stellar reviewer moment 14:00 Rockefeller, CXCR3, and three splice variants that weren't the same 17:00 NIH and the pull toward a 30,000-foot view of the field 21:00 COVID, redundancy, and the 250 GPCRs nobody studies 23:08 Building the Dr. GPCR ecosystem 32:28 Q&A — preparing an episode, funding, and what's next 46:53 Recording Brian Roth from a Prius — the closet-studio origin story Selected Quotes "You have 400 non-olfactory GPCRs. Only about 166 of them are being targeted and studied for clinical applications. But you have 250-plus receptors that are not well characterized enough and are not considered for the treatment of any diseases." "If you want to advance the field and you want to drug GPCRs better, the point is not to show that you can pipette, but the point is to get to that result." "At NIH, I decided that I wanted to go what you'd call the dark side, which I don't think it's the dark side." "Brian throughout his career was told so many times that he should quit science. And thank God he did not quit science. That's the kind of story that I like to share in the podcast." About this episode GPCRs have played a central role in my scientific career ever since I took Dr. Michel Bouvier’s class as an undergraduate student at the University of Montreal in early 2000. During the past 2 decades, my research mainly focused on chemokine receptor structure/function relationships. For the purposes of this presentation, I will walk you through my various career experiences and include the skills I learned during each experience, which ultimately led me to found Dr. GPCR. Last, I will give an overview of the various programs we established at Dr. GPCR, present our team as well as provide you with a sneak peek of our future podcast guests and more. I gave a talk on October 12th at the 3rd ERNEST meeting about the Dr.GPCR Ecosystem . I want to say thank you to the ERNEST meeting organizers for the invitation with special thanks to Dr. Martha Summer and Dr. Alexander Hauser , and Luise Wagner . For more information about the ERNEST network, visit https://ernest-gpcr.eu/ . Dr. Yamina Berchiche on the web D r. GPCR Ecosystem Member Website LinkedIn Publications Twitter Facebook Dr. GPCR Ecosystem Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Dr. Aurélien Rizk About Dr. Aurélien Rizk "Dr. Aurélien Rizk is a scientist and entrepreneur in drug discovery. He is Chief Scientific Officer and co-founder of InterAx Biotech, where he specializes in the development of a technology platform deciphering cell signaling pathways combined with AI-based approaches to elucidate structure to signaling relationship. During four years of postdoctoral research at ETH Zurich and the Paul Scherrer Institute in Switzerland, under the guidance of Prof. Gebhard Schertler, he developed methods for kinetic mathematical analysis of GPCR signaling. He also worked on creating novel methods for systems biology using temporal logic specifications while pursuing his Ph.D. at INRIA Paris-Rocquencourt, France. Before focusing on the development of innovative mathematical modeling and simulation methods for drug discovery, Dr. Aurélien Rizk co-founded Algorizk, a company that created real-time physics simulations for education, serving over 1 million users. His academic background includes studies in mathematics, physics, and computer science at the French Grande École, École Normale Supérieure de Cachan." Dr. Aurélien Rizk on the web InterAx Biotech Paul Scherrer Institut The Org LinkedIn Google Scholar Dr. GPCR AI Summary AI-generated content may be inaccurate or misleading. Always check for accuracy. Quick recap Yamina Berchiche and Aurelien Rizk engaged in a conversation about their professional backgrounds and current projects. They explored the potential of merging mathematical models with biology, the complexities of GPCRs within cells, and the applicability of technology to other fields. They also discussed the founding of a company focused on GPCRs, the transition from academia to the biotech sector, the evolution of a company that started with the development of technologies combining mathematical methods and a wet lab, and the importance of interdisciplinary teamwork in drug and technology development. They emphasized the significance of mathematical models in systems biology and pharmacology and the challenges of transferring information between different families of GPCRs. They wrapped up the conversation by discussing job opportunities at Interax Biotech and their anticipation for future interactions. Summary Professional Backgrounds and Projects Discussed Yamina Berchiche and Aurelien Rizk had a conversation about their professional backgrounds and current projects. Aurelien Rizk, a co-founder and CEO of Interax Biotech, shared about the company's development of a discovery platform for GPCRs and their focus on signaling pathways. He also talked about his past experiences in mathematics, physics, and computer sciences, and his involvement in developing mathematical models for various systems. The discussion concluded without any clear decisions, action items, or open questions. Integrating Mathematical Models and Biology: A Fascinating Discussion Yamina and Aurelien Rizk had a conversation about the importance of merging mathematical models and biology. They highlighted that while there was a time when biology lagged due to the lack of appropriate tools, it is now progressing faster. They found it fascinating to integrate both fields and the potential it holds. Aurelien Rizk mentioned the importance of being able to test and adjust predictions in real-life scenarios. They also touched upon the transferability of this approach across different systems, which Yamina found attractive. GPCRs, Software, and Fluid Dynamics Yamina Berchiche and Aurelien Rizk discussed the complexities of GPCRs within cells and the potential for applying models from one system to another. Yamina also questioned Aurelien Rizk about his interest in software, computer science, and mathematics. Aurelien Rizk shared his journey of using these disciplines in biology and how his company, Interax, came to be. The discussion ended with Aurelien Rizk sharing his current work on numerical simulations of fluid dynamics. GPCRs: A Focus for New Company Aurelien Rizk and Yamina Berchiche discussed the founding of a company focused on GPCRs and the potential applicability of the technology to other fields. Aurelien Rizk shared that he had always focused on GPCRs but had also worked on other types of receptors, indicating that the technology could be applied broadly. Yamina asked if there was ever a consideration to work on targets other than GPCRs, to which Aurelien Rizk explained that they chose GPCRs due to their wide application and potential impact. The conversation concluded with Yamina asking if Aurelien Rizk had a favorite GPCR to work on, though his response was not included in the transcript. Cell Signaling and Cancer Metastasis Discussion Aurelien Rizk and Yamina Berchiche had a detailed conversation about the intricacies of cell signaling and chemokine receptors. Yamina shared her research experience, emphasizing the fascination of understanding how cells respond to gradients and signals, particularly in relation to cancer metastasis. Aurelien Rizk also contributed to the conversation, highlighting the complexity of the process. However, the transcript is somewhat unclear and disjointed, making it difficult to summarize the specific points discussed. Academia to Biotech: Strategic Planning and Interdisciplinary Approach Yamina Berchiche and Aurelien Rizk discussed the differences between academia and the biotech industry, with Aurelien Rizk sharing his experiences transitioning from academia into the biotech sector. They highlighted the strategic importance of planning in the biotech sector due to limited funds and the need to show positive results when securing new investments. Aurelien Rizk also mentioned the interdisciplinary nature of his company, which includes mathematics, signaling pathways, a wet lab for data generation, and AI and computational chemistry. The discussion also touched on recent changes in leadership at Aurelien Rizk's company, with the introduction of a new CEO a year ago and the valuable contributions of Mark Levick, a former reviewer for the European Medicines Agency and CEO of a biotech company. Technology Evolution and Ligand Residence Time Prediction Yamina Berchiche and Aurelien Rizk discussed the evolution of the company, which started with the development of technologies combining mathematical methods and a wet lab to ensure the technology functioned. They validated their technology and made collaborations for expertise on chemokine receptors. The conversation also revolved around the company's ability to predict the residence time of a ligand and its potential correlation with a therapeutic effect or activation of a specific signaling pathway. The discussion concluded with the idea that ligand residence time could be an important factor in effective therapy. Therapeutic Effect and Receptor Interactions Aurelien Rizk and Yamina had a detailed discussion about the importance of gaining more information about the therapeutic effect in patients or animals and the dynamics of receptor interactions. They emphasized the need to quantify the dynamics of the pathways and the residence time of the receptor. Yamina raised a question about the transferability of information between different families of GPCRs and the possibility of generating a mathematical model for potential patterns. They also discussed the challenges of system dependency in data and the need to express data in a uniform way to apply models. Mathematical Models in Systems Biology and Pharmacology Aurelien Rizk and Yamina discussed the importance and relevance of mathematical models in systems biology and pharmacology. They reminisced about previous meetings and events, including a GPCR retreat where Terry presented his work. Yamina mentioned her struggle with the mathematical aspects of Terry's papers but acknowledged their importance in quantifying and removing system biases. They also discussed plans to offer a course with Terry, due to high interest. Towards the end, Aurelien Rizk shared his top three 'aha' moments as a scientist, emphasizing the importance of learning and controlling systems. Interdisciplinary Teamwork and Drug Development Yamina Berchiche and Aurelien Rizk emphasized the significance of interdisciplinary teamwork in drug and technology development, noting the challenges of communication and collaboration across different fields. They also shared their preference for small molecule therapies over protein therapeutics. Aurelien Rizk confirmed his attendance at the upcoming GPCR-Targeted Drug Discovery Summit in Boston. The discussion concluded with a brief overview of job opportunities at Interax Biotech, with Aurelien Rizk and Yamina clarifying that job openings are communicated via email and through their job board. They expressed their anticipation for future interactions. Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Dr. Stuart Maudsley About Dr. Stuart Maudsley Stuart graduated from the University of Leeds in the U.K. with a First Class Honors degree in Pharmacology. At the end of his studies, he was awarded the Pfizer Prize for undergraduate research. He then completed his Ph.D. at Leeds as well as the University’s Ackroyd, Brotherton, and Brown Scholar. Following his Ph.D., Dr. Maudsley was awarded a Howard Hughes Medical Institute Fellowship to train with Professor Robert Lefkowitz at Duke University. Following this tremendous experience, he was recruited to be the Principal Investigator of the Receptor Biology Section at the Medical Research Council (MRC) -Human Reproductive Sciences Unit within the University of Edinburgh. At the MRC he developed novel prostate cancer therapeutics based upon his research into GPCR pluridimensional signaling. To broaden his biomedical skill-set Stuart next accepted the position of Head of the Receptor Pharmacology Unit at the National Institutes of Health – National Institute on Aging at the Johns Hopkins University Medical Center. At the NIH he was the recipient of the coveted NIH ‘Bench-to-Bedside’ Translational Research Grant Award, one of the few awards available within the intramural NIH program. Upon starting a new family, and returning to Europe, Dr. Maudsley continued his scientific journey with the award of the highly-valued Odysseus Program Type I Program Grant to work as both the Adjunct Director of the VIB Center for Molecular Neurology and also Vice-Chair of the Department of Biomedical Sciences at the University of Antwerp. Stuart’s current research, in the Receptor Biology Lab, focuses on the development of novel GPCR-based therapeutics that interdict diseases based on their gerontological underpinnings. This research stream is now forming the basis of a new technology-based start-up company, HeptOME , to help screen and develop novel longevity/disease-regulating compounds with multidimensional disease efficacy profiles. Dr. Stuart Maudsley on the web Maudsley Lab LinkedIn Google Scholar ResearchGate Maudsley Lab on Facebook Receptor Biology Lab Facebook Group Twitter Semantic Scholar Instagram Neurotree Dimensions Reddit Dr. GPCR Ecosystem Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Dr. Sai Prasad Pydi About Dr. Sai Prasad Pydi Dr. Sai Prasad Pydi obtained his Ph.D. from the University of Manitoba – Canada, where he was introduced to G protein-coupled receptors (GPCRs) by Prof. Prashen Chelikani . His doctoral research focused on the structural and functional characterization of bitter taste receptors (T2Rs). In 2014, Dr. Pydi joined Dr. Jurgen Wess’s lab at the National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK) - NIH, USA as a postdoctoral fellow and trained on understanding the physiological role of GPCR signaling and beta-arrestins in diabetes and obesity. In February 2021, Dr. Pydi joined BSBE department at IIT-Kanpur. The main target of Dr. Pydi's laboratory is to develop GPCR-based drugs for the treatment of obesity and Type 2 Diabetes (T2D) by exploring metabolically important signaling pathways in immune cells and insulin-sensitive tissues (liver, pancreas, skeletal muscle, adipose tissue, and brain). His laboratory uses knock-out and transgenic mouse models, along with different cell culture systems, to understand the role of immune cell GPCRs and their cross-talk with other insulin-sensitive tissues regulating glucose and lipid metabolism. Dr. Sai Prasad Pydi on the web Molecular Metabolism & Cell Signaling Laboratory Website Twitter.com Research Gate PubMed Google Scholar Dr. GPCR Ecosystem Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

How academia and biotech collaborate to scale GPCR tools—covering fluorescence assays, GPCR internalization, and real-world distribution. Episode 3 of 3. << Back to podcast list Strategic Partner(s) Scaling GLP 1 Receptor Tools Through Academia Industry Collaboration How do GPCR tools move from individual academic labs into broad use across the research community? In this episode of the Dr. GPCR Podcast , leaders from academia and biotech unpack what effective collaboration really looks like when developing, validating, and distributing GPCR research tools. Joining the conversation are Maria Majellaro (CSO and co-founder of Celtarys Research), Johannes Broichhagen, and David Hodson. Together, we discuss how gpcr drug discovery advances when chemists, biologists, and industry partners align around rigor, trust, and accessibility. The episode explores gpcr internalization , fluorescence-based probe design, and how functional assay development benefits from scalable distribution rather than ad-hoc sharing. Listeners will walk away with a clearer view of how academic innovation translates into tools for high-throughput screening , and why availability can be as impactful as discovery itself. Why This Matters How GPCR tools lose impact when distribution and access aren’t planned from the start Why fluorescence-based assays outperform antibodies for studying receptor localization and trafficking What changes when academia and biotech share priorities instead of working in parallel When industry partnerships become essential for reproducibility and scale The moment when availability—not innovation—becomes the bottleneck in GPCR research Who Should Listen This episode is for scientists and leaders who are: Navigating the transition from academic tool development to real-world adoption Balancing innovation with validation in GPCR assay design Building reagents that must work in complex tissues, not just simplified models Exploring academia–industry collaboration but want to understand how it works in practice This conversation is part three of a three episode series produced in collaboration with our partners at Celtarys Research . 🎧 Listen to Part 1 with Dr. Hudson 🎧 Catch up on Part 2 with Dr. Broichhagen About the Guests Maria Majellaro, PhD Dr. Maria Majellaro is the Chief Scientific Officer and co-founder of Celtarys Research , a biotech spin-off from the University of Santiago de Compostela focused on advanced fluorescent ligands and GPCR research tools. She earned her PhD in medicinal chemistry from the University of Bari in 2018, including research training at the CIQUS Research Center in Spain. Following her PhD, she joined Prof. Eddy Sotelo’s group at CIQUS as a postdoctoral researcher, where the scientific foundations of Celtarys were established. Since co-founding the company in 2021, she has led all scientific activities, from proprietary technology development to international collaborations and funded research projects. Her work centers on GPCR modulators, synthetic chemistry, and enabling robust biological assays through high-quality chemical tools. Johannes Broichhagen, PhD Dr. Johannes Broichhagen is a group leader at the Leibniz Research Institute for Molecular Pharmacology (FMP) in Berlin. Trained as a chemist, he studied at the University of Erlangen–Nuremberg and completed his PhD at LMU Munich, followed by postdoctoral research at EPFL in Switzerland. His research focuses on bottom-up chemical tool development for imaging and interrogating GPCRs and other cell-surface proteins in complex biological systems. By combining fluorophore design, ligand chemistry, and pharmacology, his work enables precise visualization of receptor localization, dynamics, and function across tissues. David Hodson, PhD Dr. David Hodson is the Robert Turner Professor of Diabetic Medicine at the University of Oxford and a leading expert in metabolic GPCR biology. Originally trained as a veterinary surgeon, he conducted postdoctoral research at the CNRS in Montpellier before establishing independent laboratories at Imperial College London and later the University of Birmingham. His research focuses on class B GPCRs, including the GLP-1 and GIP receptors, with an emphasis on understanding how these receptors operate within complex tissues such as the pancreas and brain. By integrating advanced tools and translational biology, his work directly informs therapeutic strategies for diabetes and obesity. Guests on The Web Maria Majellaro LinkedIn ResearchGate Ecosystem Johannes Broichhagen LinkedIn Google Scholar Lab Website Leibniz Research Institute for Molecular Pharmacology (FMP) Profile David Hodson Radcliffe Department of Medicine Islet Biology Lab University of Birmingham Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Dr. Kathleen Caron About Kathleen M. Caron Kathleen M. Caron, Ph.D. is the Frederik L. Eldridge Distinguished Professor and Chair of the Department of Cell Biology & Physiology at The University of North Carolina at Chapel Hill—a large, interdisciplinary basic science department currently ranked 1st in the Nation in NIH funding. Dr. Caron received a BS in Biology and BA in Philosophy at Emory University and a PhD at Duke University while training with Dr. Keith Parker to elucidate the role of steroidogenesis in regulating sexual determination and adrenal and gonadal development using genetic mouse models. She pursued postdoctoral training with Nobel Laureate Dr. Oliver Smithies at UNC-CH, where she was the first to discover the essential role of adrenomedullin peptide for embryonic survival. With a special emphasis on G protein coupled receptors and receptor activity modifying proteins in vascular biology, the Caron laboratory has gained valuable insights into the genetic basis and pathophysiology of lymphatic vascular disease, preeclampsia and sex-dependent cardiovascular disease. Dr. Caron has received numerous awards including a Burroughs Wellcome Fund Career Award in the Biomedical Sciences, an Established Investigator Award and an Innovator Award from the American Heart Association, a Jefferson Pilot Award in Biomedical Sciences and a UNC-CH Mentoring Award. She currently serves as Associate Editor of Physiological Reviews; the #1 ranked journal in Physiology (IF 46.5). Dr. Caron is also past Associate Editor at JCI and served as the inaugural Associate Editor at ACS-Pharmacology and Translational Science. Dr. Caron currently holds multiple scientific advisory roles in academia, industry and the National Institutes of Health. Kathleen M. Caron on the web Lab Website Twitter Pubmed Google Scholar Orcid Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Dr. Caron Tribute Part 3 About Marc Caron Dr. Caron and his family moved to Durham, NC in 1977, following receipt of his BSc in Chemistry from Laval University and his Ph.D. from the University of Miami. He joined the faculty of Laval University School of Medicine in 1975 and then returned to join Duke’s faculty, where he remained as a James B. Duke Professor until his death. He and his laboratory members studied the mechanisms of action and regulation of hormones and neurotransmitters and how they might underlie brain and behavior disorders such as schizophrenia, Parkinson's disease, attention-deficit hyperactivity disorder, mood disorders, and addiction. Among his many honors, Dr. Caron was an investigator of the Howard Hughes Medical Institute from 1992 to 2004, a member of the American Academy of Arts & Sciences, a fellow of the American Association for the Advancement of Science, and a recipient of the Julius Axelrod Award. An authoritative and prolific scientist, with over 650 scientific publications, he is most beloved as a mentor and his relentless encouragement that shaped the careers of hundreds of scientists worldwide. About our panelists in alphabetical order and the year they first met Dr. Caron Dr. Jean Martin Beaulieu (2003) Dr. Laura Bohn (1999) Dr. Kathleen Caron - Co-host- (1970) Dr. Henrik Dohlman (1987) Dr. Kafui Dzirasa (2006) Dr. Yasushi Masuda (2004) Dr. Marco Pardo (2002) Dr. Vania Prado (2002) Dr. Amy Ramsey (2008) Dr. Bryan Roth (current) Dr. Ali Salahpour (2007) Dr. Lauren Sloksy (2020) Dr. Josh C Snyder (2012) Dr. William Wetsel (current) Memories our panelists shared with us https://video.wixstatic.com/video/93ce84_656bd30f2f964a8bbfc27d4b7815c38d/1080p/mp4/file.mp4 Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

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Eleonora Comeo synthesizes fluorescent ligands to watch adenosine receptor pharmacology happen in living cells - and explains why targeting these receptors keeps failing. << Back to podcast list Strategic Partner(s) Eleonora Comeo: Fluorescent Ligands and the Pharmacology of Adenosine Receptors Adenosine receptors are among the most studied GPCRs in the human body - and among the most difficult to drug. The four subtypes, A1, A2A, A2B, and A3, are expressed across virtually every tissue and implicated in conditions ranging from Parkinson's disease to ischemic heart disease to cancer. Over 40 crystal structures of the A2A receptor alone have been deposited in the Protein Data Bank. Clinical trials have run for decades. And yet approved therapies that selectively target these receptors remain remarkably scarce. One reason is that selectivity in this family is not just a matter of receptor subtype. It is also a matter of G protein coupling, tissue context, and the signaling assay used to measure affinity in the first place - measurements that shift depending on the experimental system. Eleonora Comeo, PhD candidate at the University of Nottingham and the Monash Institute of Pharmaceutical Sciences, is developing fluorescent ligands to address that gap directly - tools designed to visualize adenosine receptor pharmacology at the single-cell level, in environments that better reflect where these receptors actually work. For Comeo, who entered GPCR research without any background in the field and built her PhD around chemistry she could hold in her hand and watch working in a cell, the tools are both scientific instruments and the reason she stayed. ABOUT THE GUEST Eleonora Comeo is a PhD candidate jointly enrolled at the University of Nottingham and the Monash Institute of Pharmaceutical Sciences, working across the groups of Barrie Kellam and Steve Hill. A trained medicinal chemist and pharmacist, her research focuses on the design and synthesis of fluorescent ligands for adenosine A1 and A2A receptors, with the goal of developing chemical tools capable of interrogating receptor pharmacology in physiologically relevant cellular environments. Her work integrates organic synthesis with NanoBRET, SNAP-tag labeling, confocal microscopy, and super-resolution imaging to study receptor localization, internalization, and binding at endogenous and heterologously expressed levels. SCIENTIFIC THEMES OF THE CONVERSATION Fluorescent ligands as pharmacological tools - how synthetic chemistry produces molecules that make receptor behavior visible Adenosine receptor subtype pharmacology - the four subtypes, their G protein coupling profiles, and why ubiquity creates selectivity problems The tumor microenvironment and adenosine-mediated immune suppression - why A2A and A2B are being targeted in oncology Assay dependency and the instability of affinity measurements across experimental systems Endogenous receptor expression in heterologous cell systems - how HEK cell biology confounds fluorescent ligand screening Receptor dimerization - from A2A/dopamine D2 in Parkinson's to A1/A2A in cardio protection, and what remains unresolved KEY INSIGHTS FROM THE CONVERSATION 1. Visibility changes what pharmacology can ask Fluorescent ligands do more than confirm receptor binding - they allow researchers to follow receptors through internalization, track membrane localization, and observe behavior at the single-cell level using super-resolution imaging. Comeo describes the moment she saw her synthesized ligand labeling the cell membrane as one of the most rewarding points in the PhD, precisely because it closed the loop between synthesis and function in a way that binding numbers alone cannot. 2. Ubiquity is adenosine pharmacology's greatest liability The same properties that make adenosine receptors scientifically compelling - their presence in nearly every tissue, their involvement in nearly every major disease class - are what make selective targeting so difficult. Activating or blocking an adenosine receptor for one indication routinely produces off-target effects in another tissue, because the receptor is already doing something important there. The clinical attrition rate in this family reflects that problem more than it reflects a failure of chemistry. 3. Affinity is not a fixed property - it is assay-dependent The apparent affinity of adenosine for its own receptors shifts depending on which downstream signaling endpoint is being measured. A cAMP assay and a binding assay using the same receptor and the same ligand can return different affinity values. Comeo points to this as an underappreciated complication in the field - one that matters not just for scientific interpretation but for how pharmacological classifications like "low affinity" and "high affinity" are assigned across the A2A and A2B subtypes. 4. Tumor cells use adenosine receptors to silence the immune response In the tumor microenvironment, adenosine concentrations are abnormally high. That excess adenosine activates A2A and A2B receptors expressed on immune cells - and that activation suppresses the immune response, allowing tumors to grow unchallenged. Dual A2A/A2B antagonists are now in clinical trials specifically to interrupt this mechanism. Comeo describes this as one of the areas where she most hopes the field can finally validate the receptors as clinical targets, after years of trials that have not delivered. 5. HEK cells are a known confound that still catch researchers out HEK cells endogenously express A2A and A2B receptors at meaningful levels - a fact that complicates fluorescent ligand screening, binding assays, and any experiment where receptor selectivity is the question. Comeo's work uses selective antagonist controls and NanoBRET-tagged receptor constructs to distinguish transfected receptor signal from endogenous background. She also describes recent work in her group using CRISPR-edited cell lines to express receptors at endogenous promoter levels, producing reliable NanoBRET signal even at physiological expression - a methodological advance with implications for how the field studies GPCRs in native-like contexts. 6. Receptor dimerization raises questions the standard pharmacology framework does not address Adenosine receptors form both homodimers and heterodimers with other GPCRs, including A2A with dopamine D2 (a complex investigated extensively in the context of Parkinson's) and A1 with A2A (under investigation for cardioprotection in ischemic heart disease). The biological implications of many of these complexes are still being resolved. During the conversation, an unresolved question surfaced: when a tagged receptor is transfected into HEK cells that endogenously express the same or related subtypes, can the exogenous and endogenous receptors dimerize - and if so, does that alter the pharmacological readout? Neither Comeo nor the host claimed an answer. The question remains open. 7. The hardest transition in a PhD is learning that not knowing the answer is the point Comeo describes the shift from undergraduate training - where not knowing the answer is a liability - to doctoral research, where not knowing the answer is the entire reason the project exists. It is, she notes, a more difficult transition than it sounds, and one that takes time to internalize. The advice she offers to incoming PhD students centers not on technique but on disposition: stay curious about what others are working on, ask for help without embarrassment, and accept that the project is a shared endeavor even when it feels isolating. EPISODE TIMELINE Timestamps are AI-generated from the transcript and should be verified against the final edited audio before publication. 00:00 Introduction 00:44 From Bologna to Nottingham - following her heart into GPCR research 06:49 One year at Monash - starting fresh on the other side of the world 10:02 Adenosine receptor pharmacology and the challenge of targeting four subtypes 16:56 A2A vs A2B - affinity differences, tumor microenvironment, and immune escape 22:08 Why affinity measurements shift depending on the assay 27:09 Synthesizing fluorescent ligands - from crystal structures to glowing molecules 31:03 Following receptors into the cell with super-resolution imaging 36:25 Receptor dimerization - A2A/D2 in Parkinson's, A1/A2A in cardioprotection, and one open question 41:26 Finishing the PhD - what comes next and what she'll miss 42:42 Advice for PhD students - resilience, collaboration, and not fearing the unknown 54:44 The dopamine rush that keeps scientists coming back SELECTED QUOTES "I completely fell in love with that research. And I felt three months wasn't enough for me. So I asked whether they had a PhD opportunity - and here I am." "Just because you can see them. They're really useful because you can see them - you can use them to visualize the process you're interested in. That's what makes it so rewarding." "It's important to understand, in your cellular context, what the expression of the other receptor is - the one you're interested in - because otherwise you can get confounding outputs." "In chemistry, it's like when you finally see the NMR of your structure without anything but your compound - it's just perfect. You can feel the shivering behind your spine. You would just like to run around screaming." About this episode Eleonora Comeo is a doctoral candidate in Medicinal Chemistry and Drug Discovery in the joint program of the University of Nottingham in the UK and Monash University in Australia. We sat down to chat about GPCRs, synthesizing labeled ligands, and her unique position that allows her to work with GPCR scientists on 2 continents. We also touched on how COVID-19 affected her Ph.D. work. Eleonora Comeo on the web LinkedIn ResearchGate Pubmed Google Scholar Dr. GPCR Ecosystem Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Anything BUT GPCRs with Dr. Mikel Garcia-Marcos About Dr. Mikel Garcia-Marcos "I was trained as a biochemist and molecular biologist during my Ph.D (2005) in Spain and Belgium, and subsequently as a cell biologist during my postdoc (2006-2011) with Dr. Marilyn Farquhar (UC, San Diego), a pioneer of modern Cell Biology. All my formal training was in the area of signal transduction, and I continued to work on this area since I established my own laboratory in the Department of Biochemistry at Boston University in 2012. My research aims to understand the mechanisms and consequences cell communication via heterotrimeric G-proteins (Gαβγ) because they represent major intracellular hubs of signaling with very direct biomedical relevance. To achieve this goal, we use a wide range of established approaches (biochemistry, cell biology, genetics) and experimental systems (purified proteins, cultured cells, model organisms) in combination with the development of novel tools (biosensors, chemogenetics, optogenetics). Our ongoing efforts have direct implications in cancer, embryonic development defects, and neurological disorders." AI Summary In the podcast episode "Anything but GPCRs" featuring Dr. Mikel Garcia-Marcos, the host Yamina explores Dr. Garcia-Marcos's academic journey, which spans training in Spain, Belgium, and a postdoctoral fellowship at UC San Diego, where he navigated a career focused on G protein-coupled receptors (GPCRs) while aiming to maintain broad scientific interests. Dr. Garcia-Marcos shares insights on transitioning from postdoctoral research to leading his own lab, addressing the challenges of applying for academic positions and the importance of networking, adaptability, and mentorship in fostering a collaborative research environment. The conversation further delves into the dynamics of managing a diverse team, emphasizing the role of personality assessments in enhancing team cohesion and performance. Dr. Garcia-Markos reflects on milestones in his research journey, reinforcing the passion that drives scientists in the GPCR field, and engages listeners to connect with the podcast for a richer community experience. Dr. Mikel Garcia-Marcos on the web Boston University LinkedIn Dr. GPCR Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

Dr. Graciela Piñeyro on what happened when her lab tested biased agonism at the μ-opioid receptor across 25 ligands, why δ-opioid receptors recycle from the lysosome, and the quantitative pharmacology that turned an early artifact into a career of receptor work. << Back to podcast list Strategic Partner(s) Graciela Piñeyro: Partial Agonism, Receptor Recycling, and the Limits of Bias For over a decade, biased agonism at opioid receptors offered a clean route to analgesics without the respiratory depression and tolerance that have defined opioid therapy. If the right ligand could engage G-protein signaling while sparing β-arrestin, pain relief might finally be separable from side effects. In this conversation, Dr. Graciela Piñeyro — who leads an opioid receptor pharmacology group at the CHU Sainte-Justine Research Center and the Université de Montréal — walks through what happened when her lab tested that hypothesis rigorously. Across 25 ligands profiled at the μ-opioid receptor, the team found no bias, only partial agonism. Recent β-arrestin knockout work from Australia, Germany, and the UK has converged on a similar sobering conclusion. The conversation also traces her earlier work showing that δ-opioid receptors recycle from the lysosome — the compartment meant to degrade them — and how recycling patterns, not internalization itself, predict analgesic tolerance. For Dr. Piñeyro, a physician-turned-pharmacologist whose early project in Michel Bouvier's lab felt like "torture" until the right quantitative model turned her artifacts into real pharmacological responses, the throughline has never been building a career. It has been a refusal to treat messy data as noise until the right math arrived to make sense of it. About the Guest Dr. Graciela Piñeyro is a principal investigator at the CHU Sainte-Justine Research Center and a professor in the Department of Pharmacology and Physiology at the Université de Montréal. Trained as a physician in Uruguay, she began doing research in the only way then available to her — through a medical pharmacology department studying how benzodiazepines and alcohol affected sleep architecture. She completed her PhD at McGill University with Claude de Montigny, working on serotonin and antidepressant mechanisms, and her postdoctoral training with Michel Bouvier at the Université de Montréal, where she shifted into opioid receptors. Her lab now studies δ- and μ-opioid receptor signaling, biased agonism, receptor trafficking and recycling, and more recently the cannabinoid entourage hypothesis — combining BRET-based biosensors, quantitative pharmacology, and clustering approaches to connect in vitro signaling signatures to clinical side-effect profiles. Scientific Themes of the Conversation The limits of biased agonism at the μ-opioid receptor — and why partial agonism keeps explaining what bias was supposed to δ-opioid receptor recycling from the lysosome — and why the post-internalization fate of a receptor predicts tolerance better than internalization itself Protean agonism and multiple active conformations — how the same ligand can behave as agonist or inverse agonist depending on receptor tone Quantitative pharmacology as rescue operation — using operational models and BRET-based biosensors to pull pharmacological signal out of what first looks like experimental noise The defense of simple systems — why HEK-cell data can still predict FDA pharmacovigilance outcomes, and where iPSC-derived somatic systems actually pay their cost The cannabinoid entourage hypothesis as a pharmacological question — turning folkloric claims about complex mixtures into testable quantitative work Key Insights from the Conversation Twenty-five μ-opioid ligands produced partial agonism, not bias. When Dr. Piñeyro's lab systematically compared G-protein and β-arrestin recruitment across 25 compounds — standard opioids and new ligands from Pfizer — they could not identify a ligand-bias signature. What they could do was classify the compounds by relative efficacy, and that classification alone predicted clinical side effects. β-arrestin is not the villain it was made to be. Newer knockout work from groups in Australia, Germany, and the UK has shown that respiratory depression from opioids persists in β-arrestin-null mice. The mechanistic story that guided a decade of biased-ligand drug discovery needs rebuilding from the underlying biology, not from the pathway labels. The δ-opioid receptor recycles from the lysosome, and the recycling pattern determines tolerance. Long treated as a non-recycling receptor destined for degradation, the δ-opioid receptor can in fact return from the lysosomal compartment. In Dr. Piñeyro's framework, the ligands that permit recycling are the ones that produce less tolerance, whether acute or chronic — an inversion of the older view that internalization itself was the key variable. A quantitative model can turn an artifact into pharmacology. Early in her postdoc, Dr. Piñeyro watched the same ligand behave as an agonist under one condition and an inverse agonist under another. The resolution came not from a new experiment but from a model — protean agonism, as Kenakin had just described it, combined with André deLéan's software for estimating active receptor conformations — which revealed that the apparent contradiction was a quantitative signature of multiple active conformations. HEK cells still earn their keep. Even as the field pushes toward iPSC-derived somatic systems, HEK-cell signaling profiles of μ-opioid ligands correctly predicted outcomes logged in the FDA pharmacovigilance database. Dr. Piñeyro argues that the predictive power of the simpler system, and the real cost of the more elaborate one, should be weighed honestly before the field walks away from what works. The cannabinoid entourage hypothesis deserves a rigorous test. Instead of treating cannabinoids as single molecules, her group is asking whether complex mixtures of cannabinoids and terpenes produce analgesic responses that pure compounds cannot — and whether the mechanism involves allosterism across GPCRs, TRPs, and enzymes of the endocannabinoid system. The open question about THC's long-term effects on adolescent cognition sits alongside the analgesic one, and both require the same quantitative discipline. Follow the questions, not the career. Asked what advice she gives young scientists, Dr. Piñeyro's answer is blunt: she does not think of herself as having built a career. She followed interests that pulled her. In a funding environment that rewards the opposite, the advice is harder to take than it sounds — and, in her telling, the only thing that sustained her through the years when the data refused to make sense. Episode Timeline 00:00 — Introduction 01:57 — Meet Dr. Graciela Piñeyro 02:45 — From Uruguay to McGill: the cold email that changed a career 04:40 — The closed door that opened another: landing in Bouvier's lab 05:30 — The side project that became the real work 08:22 — Protean agonism and the model that rescued the data 11:00 — δ-opioid recycling from the lysosome and the question of tolerance 14:43 — 25 μ-opioid ligands, no bias, and the β-arrestin reversal 21:11 — Receptor tuning and the quantitative discipline behind the analysis 24:25 — The case for HEK cells in an age of iPSC enthusiasm 30:40 — Cannabinoids, the entourage hypothesis, and THC in teenage brains 43:20 — Follow the question, not the career Timestamps were generated using AI for readability. Selected Quotes "We tried to look for bias and classify our drugs, new and standard drugs, according to a bias signature — but there was no bias signature. What we could do was classify our drugs according to the relative efficacies. And from those relative efficacies, we were able to predict secondary effects in the clinic." "The only idea to be able to measure and predict something will transform your artifact into a real response. So that is why I got so into the models — in order to salvage my project." "We found that the receptor is sent to the lysosomes, as it has been said — but it recycles from the lysosomes." "I do not think I have a career. What I do have is — I was interested in questions and I followed my questions. I was not building a career. I was simply following my interests." About this episode Dr. Graciela Pineyro’s love for GPCR pharmacology started in Uruguay where she first worked on the serotonin receptors. This interest in research and pharmacology took Graciela to Canada where she stayed ever since she arrived for her Ph.D. work. Graciela has done extensive work on the molecular pharmacology of opioid receptors, exploring their signaling, trafficking, and their ability to activate different signaling pathways and signaling bias. Today, Graciela and her team’s efforts are directed towards the characterization of the pharmacological properties of cannabinoids in conjunction with terpenes for pain relief. Dr. Graciela Pineyro on the web Dr. Graciela Pineyro on LinkedIn Dr. Graciela Pineyro - University of Montreal Dr. Graciela Pineyro - CHU Ste-Justine Research Centre Pineyro Lab Publications on Google Scholar Pineyro Lab on Pubmed Dr. GPCR Ecosystem Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

Dr. Maria Waldhoer on why endpoint GPCR assays miss most of what ligands do — and what kinetic pharmacological fingerprints reveal instead. << Back to podcast list Strategic Partner(s) Maria Waldhoer: Pharmacological Fingerprints and the Limits of Bias Dr. Maria Waldhoer, CSO of InterAx Biotech AG, argues that endpoint assays — the field's default way of characterizing GPCR ligands — throw away most of the information a compound actually carries. Her team at InterAx models receptor signaling pathways as systems of time-dependent equations, then runs kinetic assays to refine the models and extract ten to fifteen pharmacological parameters from what would otherwise be three endpoint numbers. The approach sits in deliberate tension with the prevailing vocabulary of bias factors and functional selectivity, and with the common dismissal of HEK293-based work as too artificial to matter. Her answer to that dismissal is partly methodological and partly personal: the proudest moment of her scientific life was designing a compound in a HEK cell from a hypothesis, putting it in an animal, and watching the effect come back exactly as predicted. The conversation traces her path from neurobiology in Salzburg through academic labs in Vienna, Copenhagen, and Graz, to six and a half years at Novo Nordisk, and into biotech at InterAx — where the next challenge is using functional fingerprints to design ligands, not just describe them. About the Guest Dr. Maria Waldhoer is Chief Scientific Officer at InterAx Biotech AG in Switzerland. Her training began in zoology and neurobiology in Salzburg, followed by a PhD on GPCRs in Michael Freissmuth's lab in Vienna and postdoctoral work with Thue Schwartz in Copenhagen and Jennifer Whistler in San Francisco. After running her own academic group in Graz, she spent six and a half years at Novo Nordisk in early drug discovery, focused on incretin receptors. She has been at InterAx since 2017, where she leads the development of a computational systems biology and AI platform that produces time-resolved pharmacological fingerprints of GPCR ligands. Scientific Themes of the Conversation Kinetic versus endpoint characterization of GPCR ligands Systems biology modeling of receptor signaling pathways Pharmacological fingerprints as multi-parameter compound descriptors Ligand residence time as a driver of drug action AI combined with functional, not only structural, data The academic-to-Big-Pharma-to-biotech trajectory Key Insights from the Conversation Endpoint assays collapse the ligand's signature. Standard assay kits that read cAMP at thirty minutes or arrestin recruitment at ten collapse time-resolved signaling into a single number. Dr. Waldhoer argues that most of what distinguishes one compound from another lives in the shape of the kinetics, not the endpoint value. Model first, pipette second. InterAx treats GPCR pharmacology the way engineers treat aircraft design: build the mathematical model of the signaling pathways first, then use controlled kinetic assays as the "wind tunnel" that refines the model. Inverting the usual order changes what the experiment can be asked to do. Three inputs can yield fifteen outputs. With a well-constructed computational model and a small set of kinetic assays, one compound on one receptor can be described by ten to fifteen pharmacological parameters — internalization rates, recycling and degradation rates, G protein affinity for the ligand-receptor complex, and more — rather than a single EC50 or a single bias number. The HEK293 cell earned its keep. Her most formative scientific moment was designing a compound in HEK293 cells from a hypothesis at Novo Nordisk, putting it in an animal, and watching the effect come back exactly as predicted. The "artificial system" critique misses what those systems do for people who know how to ask the right questions of them. Bias factor is a start, not an answer. Functional selectivity has been in the vocabulary since her PhD years in Vienna. Picking a single time point for a single pathway and computing a bias factor captures far less than looking at how several pathways evolve over time — especially for compounds with unusual kinetics. The next challenge is multi-receptor, multi-disease complexity. With comorbidities and aging populations driving drug discovery, the one-receptor-one-drug frame is increasingly inadequate. The computational tools that now describe single receptors will need to extend to how multiple receptors in the same cell, in a diseased tissue, at a particular age, interact. Young founders should not build alone. The hardest-won lesson of her biotech years: great science does not rescue a company from inexperienced management. Scientists starting companies need experienced operators around them, and the honesty to know when to bring them in — a theme she returns to as her farewell message. Episode Timeline Timestamps were generated using AI for readability. 00:00 — Opening: end-of-2020 wrap-up, January break, announcements 01:28 — Meet Dr. Maria Waldhoer, CSO of InterAx Biotech 02:19 — From zoology to GPCRs: fate, not choice 06:48 — Academia to Big Pharma: speed, scale, and decisions from above 09:58 — InterAx's pivot from arrestin biosensors to kinetic systems biology 14:31 — Why endpoint numbers miss what a ligand is really doing 16:40 — AI plus "real intelligence": functional data in drug design 21:48 — Comorbidities, aging, and the multi-receptor frontier 24:07 — "What endogenous level would you like me to mimic?" 25:26 — The HEK293 experiment that predicted the animal 31:21 — Tools for the next decade: biosensors, tissues, high-throughput structure 38:43 — Career advice for scientists eyeing industry or biotech 42:35 — On starting a GPCR company: why not too early 57:30 — Aha moments, including the EU grant pitch in Brussels 01:01:53 — "You're only as good as the other people you're with" Selected Quotes "A long way through the bright and the dark side of science." "What endogenous level would you like me to mimic?" "We combine AI with RI — with real intelligence." "You're only as good as the other people you're with." About this episode Dr. Maria Waldhoer is originally from Austria. She earned her M.Sc. in Zoology and Neurobiology before completing a Ph.D. in Biology and Pharmacology at the University of Vienna. GPCRs led Maria to Thue W. Schwartz’s lab in Copenhagen where she completed her postdoctoral training. After working in the US and at the University in Graz in Austria, Maria worked several years at Novo Nordisk before joining InterAx Biotech in Switzerland as their Chief Scientific Officer. Even though Maria stumbled upon the GPCR field, her 20 years in both academia and in the industry working on GPCRs make her a strong and dedicated scientific leader. Dr. Maria Waldhoer on the web LinkedIn InterAx Biotech Pubmed Dr. GPCR Ecosystem Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Annabelle Milner About Annabelle Milner Annabelle completed her undergraduate degree in Biomedical Sciences at the University of Bath. As part of the degree, she undertook a 1-year research-based placement at the Charles Perkins Centre in Sydney, investigating the effects of dietary carbohydrates on metabolic health with Dr. Jibran Wali. From here, she returned to the UK. She began her Ph.D. at Imperial College London with Prof Aylin Hanyaloglu, Prof Gary Frost, and Dr. Alastair Brown (Sosei Heptares), where she is currently a final year Ph.D. student. Annabelle’s Ph.D. work focuses on microbial-derived metabolites that signal through GPCRs expressed in the GI. In particular, she is looking at L- and D-lactate-activated HCAR1 signaling. She presented her Ph.D. work at the Society of Endocrinology Conference 2022 and was awarded the best oral poster prize. Outside the lab, she enjoys baking and swimming and has recently taken up paddle boarding. Annabelle Milner on the web Linkedin Researchgate Pubmed Dr. GPCR Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

< Back to Vault Title I'm a paragraph. I'm connected to your collection through a dataset. Click Preview to see my content. To update me, go to the Data Manager. This Vault is available to Dr. GPCR Premium members. Built for founders who prefer clarity over chaos and confusion. Biotech Decision Vault by Attila Foris Strategic Business & Operating Systems Advisor Dr. GPCR Ecosystem

<< Back to podcast list Strategic Partner(s) Dr. Stuart Maudsley About Dr. Stuart Maudsley Stuart graduated from the University of Leeds in the U.K. with a First Class Honors degree in Pharmacology. At the end of his studies, he was awarded the Pfizer Prize for undergraduate research. He then completed his Ph.D. at Leeds as well as the University’s Ackroyd, Brotherton, and Brown Scholar. Following his Ph.D., Dr. Maudsley was awarded a Howard Hughes Medical Institute Fellowship to train with Professor Robert Lefkowitz at Duke University. Following this tremendous experience, he was recruited to be the Principal Investigator of the Receptor Biology Section at the Medical Research Council (MRC) -Human Reproductive Sciences Unit within the University of Edinburgh. At the MRC he developed novel prostate cancer therapeutics based upon his research into GPCR pluridimensional signaling. To broaden his biomedical skill-set Stuart next accepted the position of Head of the Receptor Pharmacology Unit at the National Institutes of Health – National Institute on Aging at the Johns Hopkins University Medical Center. At the NIH he was the recipient of the coveted NIH ‘Bench-to-Bedside’ Translational Research Grant Award, one of the few awards available within the intramural NIH program. Upon starting a new family, and returning to Europe, Dr. Maudsley continued his scientific journey with the award of the highly-valued Odysseus Program Type I Program Grant to work as both the Adjunct Director of the VIB Center for Molecular Neurology and also Vice-Chair of the Department of Biomedical Sciences at the University of Antwerp. Stuart’s current research, in the Receptor Biology Lab, focuses on the development of novel GPCR-based therapeutics that interdict diseases based on their gerontological underpinnings. This research stream is now forming the basis of a new technology-based start-up company, HeptOME , to help screen and develop novel longevity/disease-regulating compounds with multidimensional disease efficacy profiles. Dr. Stuart Maudsley on the web Maudsley Lab LinkedIn Google Scholar ResearchGate Maudsley Lab on Facebook Receptor Biology Lab Facebook Group Twitter Semantic Scholar Instagram Neurotree Dimensions Reddit Dr. GPCR Ecosystem Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

Structural biologist Qing Fan describes a decade of GABA-B receptor research at Columbia - from obligate heterodimerization and the inter-subunit latch to an unexpected discovery of phospholipids inside the transmembrane bundle, and what class C GPCR architecture means for neurological disease and drug design. << Back to podcast list Strategic Partner(s) Qing Fan: Inside the Architecture of Class C GPCRs Class C GPCRs are structural and mechanistic outliers within the GPCR superfamily. Unlike class A receptors, which bind orthosteric ligands within their transmembrane domain and can function as monomers, class C receptors carry an additional extracellular domain of 500 to 600 amino acids that houses the agonist binding site - and they require dimerization as a prerequisite for function. Despite the clinical significance of their members, particularly the GABA-B receptor, the metabotropic glutamate receptors, and the calcium-sensing receptor, the molecular mechanisms governing their activation and regulation remain incompletely understood. Fan's laboratory at Columbia University has spent more than a decade investigating the three-dimensional architecture of the GABA-B receptor - the first known obligatory GPCR heterodimer - across multiple functional states. Her work has produced structural data at the extracellular domain level and, more recently, full-length cryo-EM structures in inactive conformation, leading to an unexpected discovery: phospholipids embedded inside each transmembrane bundle that appear to function as both structural anchors and negative allosteric modulators. This conversation covers the current structural landscape of class C GPCRs, how genetic disease mutations in the transmembrane domain connect to Rett syndrome and epileptic encephalopathy, and what allosteric and biased signaling strategies could offer that baclofen - the only FDA-approved GABA-B drug - cannot. Fan's commitment to this receptor began with a single structural observation during her postdoc: dimers forming in an FSH receptor crystal that she could not set aside. ABOUT THE GUEST Qing Fan is an associate professor of pharmacology and pathology and cell biology at Columbia University. A structural biologist by training, her research focuses on the three-dimensional architecture of class C GPCRs - with particular emphasis on the GABA-B receptor, which she has studied as her primary independent research question for over a decade. Her work employs X-ray crystallography, single-particle cryo-EM, mutagenesis, and mass spectrometry, often through cross-disciplinary collaboration, to connect structural findings to receptor function and disease-relevant biology. Fan's structural studies of the full-length GABA-B receptor contributed to a wave of publications that, in the same year, established inactive, active, and intermediate conformational states of this receptor using cryo-EM. SCIENTIFIC THEMES OF THE CONVERSATION The structural architecture that sets class C GPCRs apart from class A - and why that architecture makes activation harder to study Obligate heterodimerization as a functional requirement, not a regulatory option The unexpected discovery of embedded phospholipids inside the GABA-B transmembrane bundle and their role as structural and allosteric components Disease-associated mutations in the GABA-B transmembrane domain and what they suggest about precision pharmacology The therapeutic landscape of GABA-B: baclofen's limitations and the case for allosteric and biased approaches Cryo-EM as a catalyst for structural pharmacology - what it enabled and what it still cannot resolve KEY INSIGHTS FROM THE CONVERSATION Class C GPCRs carry a fundamentally different activation logic In class A receptors, the orthosteric ligand binds inside the transmembrane bundle and directly induces conformational changes that activate the receptor. In class C receptors, the orthosteric site sits inside a large extracellular domain that is physically remote from the transmembrane core. How the agonist binding event at the extracellular level is communicated downward to activate the transmembrane domain remains an open mechanistic question - and it is the central problem Fan's laboratory is trying to answer. Dimerization is not optional - it is the mechanism GABA-B is an obligate heterodimer: the GABA-B1 subunit carries the agonist binding site; the GABA-B2 subunit is required for trafficking to the cell surface and for G protein coupling. Neither subunit functions without the other. Fan's structural work identified a quartet of charged residues - salt bridges between TM3 and TM5 helices of both subunits - that she terms the inter-subunit latch. Disrupting this latch through mutagenesis produces constitutive receptor activity, suggesting it is a critical component of the receptor's inactive state. Phospholipids inside the transmembrane bundle: a discovery nobody expected When Fan's team solved the full-length cryo-EM structure of inactive GABA-B, they found a bulky phospholipid occupying the internal cavity of each TM bundle. Using mass spectrometry in collaboration with colleagues at UC Davis, they identified the exact molecular identity of both lipids and assigned one to each subunit based on head group size differences. Both lipids form extensive contacts with their respective subunits, leading Fan to propose they are necessary structural components - not incidental contaminants. Mutational analysis of the GABA-B2-bound lipid site further suggested that lipid acts as a negative allosteric modulator, though Fan is careful to note that more thorough characterization is needed before conclusions can be drawn about each lipid's specific functional role. Rett syndrome and epilepsy mutations point directly to the transmembrane domain Single amino acid mutations in GABA-B2 have been linked to Rett syndrome and epileptic encephalopathy. These mutations map to the transmembrane domain - the same region where Fan's team identified the embedded lipid binding site. The proximity raises the question of whether some disease mutations exert their effects by disrupting lipid-receptor interactions. Fan describes the resolve-the-disease-isoform-structure approach as underutilized: most structural work focuses on wild-type receptors, while patients with genetic disease are born with receptors that may behave very differently - and that may respond differently to existing drugs. Baclofen works. But its therapeutic window is narrow. Baclofen, a selective GABA-B agonist, is the only FDA-approved drug targeting this receptor. It is used to treat muscle spasticity in multiple sclerosis and spinal cord injury, but it carries significant side effects - including drowsiness and weakness - that limit its clinical utility. Fan describes the allosteric sites within the transmembrane domain as a more targeted alternative: they offer receptor modulation without directly competing with the endogenous agonist at the orthosteric site, and they map onto the same transmembrane region where disease-relevant mutations cluster. The biased agonism framework still offers real specificity - if applied carefully Fan points to the 2016 work on the mu opioid receptor by Kobilka, Gnäder, Roth, and Shokat as an illustration of what pathway-selective drug design can achieve: a compound that confers analgesia through G protein signaling while avoiding the respiratory depression associated with beta-arrestin pathway activation. She acknowledges the field's more recent reassessment of how clean that selectivity actually is in vivo - but holds that the underlying principle of fine-tuning rather than binary pathway switching remains a viable and underexplored pharmacological strategy for GPCR-targeted drug design. A decade on one receptor: the cost and the clarity it produces Fan has worked on the GABA-B receptor since it became her first independent project. Over more than ten years, the questions have deepened rather than resolved: the lipid finding opened new lines of inquiry; the disease mutation connections raised new structural puzzles; the cryo-EM structures raised as many mechanistic questions as they answered. Her description of this trajectory is not frustration - it is the argument for sustained focus. The field has moved from not knowing the subunit composition of GABA-B to holding cryo-EM structures in inactive, active, and intermediate states. That arc is the product of a community of researchers willing to stay with one system long enough to see it clearly. EPISODE TIMELINE Timestamps are AI-generated approximations based on transcript markers and may not reflect exact positions in the final edited video. 00:00 - Opening announcements 01:26 - Fan's background as a structural biologist and path to class C GPCRs 04:39 - Why class C GPCRs remain the less-explored side of the GPCR superfamily 05:11 - The architecture of GABA-B: extracellular domains, obligate heterodimerization, and field milestones since the 1970s 11:02 - The unexpected cryo-EM finding: phospholipids embedded inside each transmembrane bundle 12:55 - What the lipids actually do - structural components, allosteric modulation, and open questions 14:57 - Disease territory: epilepsy, spasticity, pain, addiction, and the limitations of baclofen 16:17 - The case for resolving disease isoform structures as a path toward precision medicine 19:03 - GPCRs as drug targets: allosteric sites, biased signaling, and what the mu opioid receptor example demonstrated 23:37 - What full-length structures in multiple states still need to deliver for drug design 25:01 - Advice for early-career scientists: the role of passion in sustained scientific work 26:15 - Three "aha" moments that shaped a career - from MHC antigen presentation to the cryo-EM revolution 29:55 - Increasing diversity in science through mentorship, structured Q&A, and institutional commitment SELECTED QUOTES "My favorite is still the GABA-B receptor since it was my first independent project and my lab has been working on it for more than a decade now." "One of our surprising findings is the discovery of a bulky phospholipid that occupied the internal cavity of each TM bundle." "Ligands that display biased signaling property may serve as highly specific drug candidates. And this feature opens more room for selecting a specific effect without also interfering with other cell processes." "I would advise young scientists to follow their interests and to work on projects that they're passionate about and not simply projects that may attract more funding. Their passion will keep them going even when they encounter difficulties." About this episode Dr. Fan is currently an associate professor of Pharmacology and Pathology and Cell Biology at Columbia University in NYC. Qing is a structural biologist interested in the molecular mechanisms controlling how class C GPCRs transmit signals. She obtained her bachelor's, master and doctoral degrees at Harvard University and completed her postdoctoral training with Dr. Hendrickson at Columbia University. Join us and learn more about Qing's work and how we powered through a technical issue during the interview. Dr. Qing Fan on the web Fan Lab Dr. Fan at Columbia University Research Gate LinkedIn Pubmed Dr. GPCR Ecosystem Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. 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