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<< 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. 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. Raul Gainetdinov About Dr. Raul Gainetdinov Raul R. Gainetdinov is the Institute of Translational Biomedicine Director at Saint Petersburg State University (SPBU), Russia. Before SPBU, Raul R. Gainetdinov was a Senior Researcher in the Department of Neuroscience and Brain Technologies at the Italian Institute of Technology in Genova, Italy (2008-2016) and an Associate Research Professor in the Department of Cell Biology at Duke University in North Carolina, USA (1996-2008). From 2013-2018, he was also a Professor at the Skolkovo Institute of Science and Technology (Skoltech), Moscow. Before joining the Department of Cell Biology in 1996 as a postdoc and becoming faculty at Duke in 2000, he researched at the Institute of Pharmacology Russian Academy of Medical Sciences in Moscow (1988-1996). He received a Ph.D. in pharmacology in 1992 from the Russian Academy of Medical Sciences and an M.D. in 1988 from the Second Moscow Medical Institute, Moscow, Russia. Since 2013, he has been elected Chair of the subcommittee for the Dopamine receptors of the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR). As of August 2022, he has over 270 publications in scientific journals (including Science, Nature, Cell, and PNAS) and co-authored 13 patents. His papers were cited over 28,000 times (H-index – 81, ISI Web of Science). In 2018-2020, Raul R. Gainetdinov was included in the Web of Science (WOS) Highly Cited Researchers (HCR) list, representing the top 0.1% of scientists worldwide. Dr. Raul Gainetdinov on the web Saint-Petersburg State University Wikipedia Google Scholar Researchgate Google 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. Josephine (Pina) Cardarelli About Dr. Josephine (Pina) Cardarelli Dr. Pina Cardarelli, CSO for GPCR Therapeutics Inc., based in South Korea, has recently been named President of GPCR Therapeutics, USA, a newly incorporated Biotechnology company in the Bay Area. The company’s mission is to discover and develop highly effective cancer therapeutics by targeting heteromers of G protein-coupled receptors (GPCR). Burixafor, their most advanced clinical candidate, will be in Phase II clinical trial next year. Additionally, they have a library of target GPCR heteromers for Oncology. Dr. Cardarelli heads the team of talented researchers that will be expanding at the US site. Dr. Cardarelli is a drug development leader with extensive experience driving drug discovery teams in bringing biologics to clinical proof of concepts. She has expertise in cell biology, pharmacology, translational medicine, oncology, immuno-oncology, immunology, and clinical development. Previously, she held the position of Vice President of Cell Biology & Pharmacology, at Bristol-Myers Squibb . She was an integral contributor to two therapeutics that are FDA approved, Yervoy and Opdivo. She was a participant in numerous due diligence (anti-CXCL8 mAb) and has managed external collaborations and alliances. Prior to this, she held the position of Vice President, at Medarex, Inc . While at BMS and Medarex, she led programs from target ID to clinical development that included, CXCL10 (Eldelumab), CXCR4 (Ulocuplumab), CD30, CD19, Fucosyl GM-1, & mesothelin-ADC, Glypican-3-ADC, CD70-ADC. She oversaw early discovery programs IL-23 p19 and IL23 p19/IL-17 bispecifics. At Medarex, she initiated and identified the lead mAb for the type I interferon-alpha receptor project, licensed to AstraZeneca (Saphnelo™ Anifrolumab) that has just received FDA approval for systemic lupus erythematosus. She has extensive experience working with Biologics, and Antibody Drug Conjugates as well as experience in IND fillings, IB updates, and responding to FDA inquiries. She is an inventor on 39 issued U.S. patents including anti-PD-1 patents, 22 EP patents, and greater than 100 global patents centered around therapeutic development. She has also authored forty-six peer-reviewed publications. Dr. Cardarelli received her Ph.D. in Physiology from Albany Medical College. Dr. Josephine (Pina) Cardarelli on the web LinkedIn Company 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 >>

Biotech founder Ajay Yekkirala shares how AI, GPCRs, and bold questions are driving next-gen pain therapeutics and drug discovery innovation. << Back to podcast list Strategic Partner(s) From Curiosity to Breakthrough: Ajay Yekkirala on GPCR Innovation What if the key to safer, more effective drugs lies in asking the right questions — and daring to challenge what’s “not possible”? In this episode, Dr. Ajay Yekkirala shares the pivotal moments that transformed him from a curious PhD student into a GPCR drug developer and entrepreneur. Dr. Ajay Yekkirala is a GPCR pharmacologist, biotech entrepreneur, and co-founder of Superluminal Medicines, a company using machine learning to unlock new GPCR-targeted therapies. In this wide-ranging conversation, he reflects on the mentors, failures, and bold questions that shaped his journey from academia to AI-powered drug discovery. Why This Matters Translating basic GPCR science into actual medicines is broken. Ajay unpacks why—and what it takes to fix it. AI is reshaping how we understand protein dynamics , but only when driven by deep biological questions. Young scientists are hungry for alternate career paths. This episode is a playbook for thinking bigger. Innovation doesn’t happen in isolation. Ajay reveals how humility, curiosity, and collaboration fuel the future of drug discovery. What You’ll Learn in This Episode How Ajay’s failed MD/PhD application rerouted his path toward a breakthrough GPCR research career The inside story behind founding Blue Therapeutics and targeting supraspinal pain pathway What it means to “teach AI protein dynamics,” and how Superluminal is using it to predict signaling bias The entrepreneurial lessons no one tells postdocs: how to pitch, fail, and build a team Why asking “what if it can be done?” is the heart of scientific innovation Who Should Listen PhD students and postdocs exploring biotech careers GPCR scientists interested in translational innovation Biotech investors and strategic leaders seeking new drug development models Anyone curious about where AI meets molecular pharmacology About Ajay Yekkirala Dr. Ajay Yekkirala is a molecular pharmacologist, biotech founder, and scientist whose career has been defined by bold questions and even bolder moves. Originally on track to pursue an MD/PhD, a rejection letter pivoted him into a PhD program at the University of Iowa, where he studied opioid pharmacology under the legendary Dr. Philip Portoghese. That “failure” became a launchpad: Ajay later joined the lab of Dr. Clifford Woolf at Boston Children’s Hospital and Harvard Medical School, where he deepened his understanding of pain biology and began dreaming bigger. Driven by the opioid crisis and the lack of non-addictive pain treatments, Ajay co-founded Blue Therapeutics, a biotech startup focused on targeting supraspinal GPCRs for chronic pain. But he didn’t stop there. Seeing the limits of traditional drug discovery, he later co-founded Superluminal Medicines, a company using machine learning to explore GPCR structure-function relationships and predict biased signaling with precision. Ajay’s work sits at the intersection of GPCR biology, AI, and translational medicine. He’s a strong advocate for cross-disciplinary thinking, mentoring young scientists, and building companies that solve real, unmet needs in human health. His story is one of relentless curiosity, humility in the face of complexity, and an unshakable belief in science’s power to do better. Ajay Yekkirala on the web Superluminal Medicines LinkedIn Tune in now to hear how asking “what if?” led Ajay Yekkirala to reshape the future of GPCR-targeted medicine. 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. Graeme Milligan About Dr. Graeme Milligan Professor Graeme Milligan is Gardiner Professor of Biochemistry, Dean of Research, and Deputy Head of the College of Medical, Veterinary, and Life Sciences at the University of Glasgow. His main research group centers on the function, structure, and regulation of G protein-coupled receptors (GPCRs) and their interacting proteins. His experience also includes translating knowledge generated into the selection of targets, screening, and identification of small molecule regulators of these proteins, and progressing such ligands in drug development programs. Prof. Milligan has published more than 550 peer-reviewed articles and his research has been cited more than 35,000 times. He was elected to the Fellowship of the Royal Society of Edinburgh in 1998 and to the Fellowship of the Academy of Medical Sciences in 2016. Prof. Milligan is the co-founder of both Caldan Therapeutics (2015) which discovers novel therapeutics for metabolic diseases including Type 2 Diabetes and other indications including non-alcoholic steatohepatitis (NASH) and inflammatory diseases and Keltic Pharma Therapeutics (2020) which is developing new treatments for malaria. Dr. Graeme Milligan on the web University of Glasgow ResearchGate PubMed Orcid Google Scholar 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) Chris Langmead Chris Langmead is Professor, Deputy Director, and Better Medicines Theme Leader of the Neuromedicines Discovery Centre at the Monash Institute of Pharmaceutical Sciences (MIPS), a collaborative venture targeting new medicines development for poorly-treated mental health disorders. He also directs a collaborative neuroscience R&D program with Servier (France) and is the co-founder and CEO of Phrenix Therapeutics, a biotech spin-out from the Neuromedicines Discovery Centre that is developing next-generation therapeutics for schizophrenia. Prior to these roles this he was Head of Pharmacology at Heptares Therapeutics Ltd., a UK-based biotechnology company (2009-2012), where he was responsible all of the company’s discovery biology. He is an acknowledged expert in drug discovery, particularly in the field of psychiatry, where he has led multiple projects into late stage preclinical development, many of which have progressed into clinical trials. These successes enabled the US$400M sale of Heptares Therapeutics Ltd. to the Sosei Group Corporation in 2015. Prior to joining Heptares, Chris was a neuroscience researcher at GlaxoSmithKline, UK (1998-2009). He has a degree and PhD in pharmacology from Queens' College, Cambridge and University College London, respectively, was the youngest person to be elected as a Fellow of the British Pharmacological Society in 2012, and was the recipient of the British Pharmacological Society Novartis Prize in 2017. Chris serves on the editorial boards of the British Journal of Pharmacology, ACS Chemical Neuroscience, ACS Pharmacology & Translational Science and Frontiers in Pharmacology. He is also a corresponding member of NC-IUPHAR. He has published over 70 research articles, reviews and book chapters on drug discovery, which have been cited over 5000 times. Christopher Langmead on the web Monash University T witter Google Scholar Linkedin PubMed Monash Neuromedicines 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. Matthew Eddy About Dr. Matthew Eddy Matthew Eddy earned his BA in Chemistry from Oberlin College, where he trained with solid-state NMR expert Professor Manish Mehta . He then earned his Ph.D. in physical chemistry from the Massachusetts Institute of Technology, training under the mentorship of Prof. Robert Griffin . Following this, Dr. Eddy began learning and investigating human GPCRs while training in the laboratories of Professors Raymond Stevens and Kurt Wüthrich at The Scripps Research Institute. Dr. Matthew Eddy on the web 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 >>

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<< Back to podcast list Strategic Partner(s) Dr. Daniel Wacker About Dr. Daniel Wacker I obtained my B.Sc. degree from the University of Munich performing work in the lab of Dr. Roland Beckmann with a brief stay at Cambridge University, UK, working in the lab of the late Dr. Kiyoshi Nagai . I then obtained an M.Sc. at the University in Munich working e.g. in the lab of Patrick Cramer . I next moved to Rockefeller University in NYC to work in the lab of the late Dr. Guenter Blobel , before starting my Ph.D. in 2009 at The Scripps Research Institute in La Jolla. There I obtained my Ph.D. in the lab of Dr. Ray Stevens in 2013 solving several GPCR crystal structures, including that of the first serotonin receptor. I then moved to UNC at Chapel Hill to do postdoctoral work in the lab of Dr. Bryan Roth where I established GPCR structural biology and learned the ins and outs of molecular pharmacology and in vitro drug discovery. In 2018 I started my own lab at the Icahn School of Medicine at Mount Sinai in NYC, where I have been working on structure-function and drug discovery of GPCRs and transporters. Dr. Daniel Wacker on the web Website LinkedIn Twitter 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) Dr. Silvia Sposini About Dr. Silvia Sposini " I'm originally from Rome, Italy, where I studied Biological Sciences as a BSc student. I moved to London as a short experience (3 months) during my MSc but I ended up staying for a full year and and a PhD! During my time in London I investigated regulatory mechanisms of GPCR action, namely dimerization and membrane trafficking, in Dr Aylin Hanyaloglu 's lab at Imperial College London. In 2018 I got married and moved to France, to join the Interdisciplinary Institute for Neurosciences in Bordeaux. Still working on GPCR trafficking but this time in neurons. In 2021 I became mum of a gorgeous baby girl, Elena. I am currently funded by a postdoctoral fellowship from Wellcome Trust, working on a collaborative project (Dr Hanyaloglu's lab at ICL + Dr Perrais' lab at IINS) focused on understanding the interplay between GPCR signalling and trafficking in neurons using microscopy and proteomics based techniques. " Dr. Silvia Sposini on the web Bordeaux Neurocampus LinkedIn ResearchGate X (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) Dr. Bruno Giros About Dr. Bruno Giros Dr. Giros' lab investigates how molecular changes at the nerve synapse might impact integrated behavior and what we might learn from these mechanisms to cure mental illness. After doctoral training at the Pierre and Marie Curie University in Paris and a short internship at Genentech Inc. in South San Francisco, he joined the CNRS as a Research Fellow in 1987 in the INSERM Laboratory directed by Jean-Charles Schwartz in Paris, where he cloned and characterized dopamine D2 and D3 receptor subtypes. From 91 to 94, he was an assistant professor at Duke University in North Carolina, working with Marc Caron and Robert Lefkowitz (2012 Nobel Prize in Chemistry) to characterize several neurotransmitter transporters and kinases and establish the first knock-out for these genes. In 1999, in France, Dr. Giros created the INSERM/CNRS laboratory on the "Neurobiology of Psychiatric Disorders," first in Créteil with Marion Leboyer, then at the University of Paris-Sorbonne with Hervé Chneiweiss. Since 2008, he has arrived at McGill University as a Canada Research Chair. At McGill, his laboratory has two main axes of research: 1) Studying interindividual vulnerability to chronic stress and depression and; 2) Understanding the role of phenotypically defined subpopulations of striatal neurons in motor and cognitive functions. Bruno Giros has trained 59 master's, doctoral and postdoc students, most of his trainees obtain positions in the academic or private sectors or are currently pursuing postdoctoral research training or have entered medical studies. Dr. Giros has published more than 200 publications with an H factor of 79 and 32,000 citations (Google Scholar) and has received several distinctions, including the CNRS silver medal, the FRM "Young Researcher" prize, the ISI “Highly Cited” and F-1000 in Pharmacology, and recently received the Heinz Lehmann Award from the Canadian College of NeuroPsychopharmacology and the distinguished James B. McGill Professor Award. Dr. Bruno Giros on the web Dougles Research Center LinkedIn Google Scholar Researchgate 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. Aaron Sato on building the synthetic antibody library that finally makes GPCRs tractable — and the greenfield strategy that led him there. << Back to podcast list Strategic Partner(s) Aaron Sato: Synthetic Antibody Libraries for the Hardest GPCR Targets GPCRs account for a substantial fraction of validated drug targets, yet most are drugged by small molecules — antibodies against GPCRs remain notoriously difficult to discover. This conversation explores how synthetic antibody phage display libraries, built on silicon-based DNA synthesis, are rewriting that constraint. Dr. Aaron Sato, CSO of Twist Biopharma, describes the motif-directed library his team developed by collecting known GPCR-binding sequences from protein, peptide, and antibody ligands and seeding them into the heavy chain CDR3 of a fully human synthetic library. The discussion covers why degenerate oligos had been the bottleneck for library quality, how a "library of libraries" strategy sidesteps the ten-billion-variant ceiling that caps any single phage library, and why the team can now move from a GPCR target to a bivalent IgG ready for functional assays in eight to ten weeks. For Aaron, this work is personal: he has built his career hunting greenfield targets where others had failed — and GPCRs were the greenfield he had been waiting for. About the Guest Dr. Aaron Sato is the Chief Scientific Officer and VP of Protein Engineering at Twist Biopharma, the biologics division of Twist Bioscience. He earned his PhD at MIT in the laboratory of Lawrence Stern, where he studied structure-function relationships of MHC class II proteins by X-ray crystallography. His career has traced the evolution of antibody engineering, with leadership roles at DIAX, Oncomed, Sutro Biopharma, and Lake Pharma before joining Twist. His current focus is building synthetic phage display libraries that drug targets the field has long treated as intractable — GPCRs chief among them. Scientific Themes of the Conversation Silicon-based DNA synthesis and the end of degenerate oligos in library design Motif-directed library design — encoding ligand-binding sequences into CDR3 architecture The library of libraries as an answer to the diversity ceiling of single phage libraries Greenfield target selection as a drug discovery strategy Family-level cross-reactivity as an advantage, not an obstacle, in GPCR antibody discovery Timelines, automation, and the industrialization of antibody workflows Key Insights from the Conversation Silicon DNA synthesis removes the degenerate oligo bottleneck. Traditional synthetic libraries rely on degenerate or trinucleotide mixtures to encode CDR diversity, which limits control over which variants actually appear. Twist's silicon platform produces pools of discrete, designed sequences — a shift in how synthetic libraries are composed. The motif-directed library encodes prior biological knowledge directly into CDR3. By curating protein, peptide, and antibody motifs known to bind GPCRs and inserting them at the top of the heavy chain CDR3, the library enters each panning campaign already biased toward the target class. The design decision is the library's main differentiator. A motif-directed library reaches targets its motifs weren't designed for. The same library has produced antibodies against orphan GPCRs and receptors without peptide ligands, because the surrounding CDR diversity provides enough variation to find binders outside the seeded motif content. Phage display's ~10¹⁰ variant ceiling can be broken by stacking libraries. Any single phage library is capped near ten billion variants. Running multiple libraries in parallel moves the effective diversity toward 10¹² — the idea Aaron calls his library of libraries. Eight to ten weeks from a GPCR target to a functional IgG is the platform's working tempo, not a best case. By skipping fragment-based screening and going directly to full bivalent IgG, the team hands functional biology teams a molecule that is ready for flow cytometry and receptor assays almost immediately. Aaron's strategy is deliberately greenfield. He looks for target classes where existing platforms have already failed — not because the biology is easier, but because new technology is rewarded most where the incumbents have stalled. GPCR family architecture is a discovery advantage. Receptors within a family share sequence and surface topography, so an antibody recovered against one member is often a legitimate starting point for discovery across the family. Episode Timeline Timestamps were generated using AI for readability. 00:00 Introduction and sponsor acknowledgment 01:53 The conversation begins 02:29 From MIT crystallography to leading Twist Biopharma 04:21 Twist Bioscience, Twist Biopharma, and the silicon DNA platform 08:12 Using DNA for long-term data storage — a parallel vertical 09:17 Why antibodies to GPCRs have stayed so intractable 09:29 The motif-directed library — encoding receptor motifs into CDR3 12:34 Why one antibody can open up a whole receptor family 14:36 Eight to ten weeks from target to tested bivalent IgG 17:21 The library of libraries — scaling past 10 billion 18:42 Who partners with Twist Biopharma today 22:45 Beyond oncology — inflammation, metabolism, cardiovascular 24:55 Running a protein engineering team through a pandemic Selected Quotes "Synthetic antibody phage display libraries are actually best used for really difficult to drug targets." "I often love to look for my greenfield areas, where there's not a lot of competition because there's just really no technology that enables you to drug specific targets." "In phage display, you're oftentimes kind of capped out around 10 billion different antibodies per library. One way around that limited diversity is to actually have multiple libraries." "GPCR antibodies are just so intractable oftentimes." About this episode In this episode of the Dr. GPCR Podcast , I spoke to Dr. Aaron Sato from Twist Biopharma , a vertical within Twist Bioscience . Aaron is currently the Chief Scientific Officer and VP of Protein Engineering. He earned his Ph.D. at the Massachusetts Institute of Technology, where he studied MHC class II structure-function relationships. His path led him to work in an industry where he assumed various responsibilities and roles in the antibody space. Aaron has a proven track record as a biologics leader as he led teams to discover and develop novel first-in-class antibody therapeutics. Dr. Sato published over 30 peer-reviewed papers and contributed to 40 issued patents in the antibody space. During our time together, Aaron and I discussed how using Twist Bioscience’s proprietary technology to manufacture DNA at a scale, the team saw an opportunity to tackle the challenge of identifying novel functional antibodies targeting GPCRs by incorporating these natural binding partners into Twist’s antibody library design. We’d like to extend a special thanks to Twist Biopharma for sponsoring this episode of the Dr. GPCR podcast. Dr. Aaron Sato on the web LinkedIn Twitter Google Scholar Twist Bioscience Twist Biopharma 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. Michael Feigin About Dr. Michael Feigin "Dr. Michael Feigin is an Associate Professor in the Department of Pharmacology and Therapeutics, and Director of Graduate Studies of Experimental Therapeutics at Roswell Park Comprehensive Cancer Center in Buffalo, NY. He earned his Ph.D. under Dr. Craig Malbon at SUNY Stony Brook studying the role of G-protein coupled receptors (GPCRs) and their regulators in the Wnt signaling pathway. Mike then joined the lab of Dr. Senthil Muthuswamy at Cold Spring Harbor Laboratory and probed the roles of polarity proteins (Feigin, et al., Cancer Research, 2014) and GPCRs (Feigin, et al., PNAS, 2014) in breast cancer pathogenesis, using mouse models, three-dimensional cell culture and computational approaches to drug target discovery. When Dr. Muthuswamy moved to the University of Toronto, Mike joined the laboratory of Dr. David Tuveson at CSHL where he participated in the development of an organoid system for the culture of normal and malignant pancreatic tissue, allowing advances in sequencing, target discovery and biomarker development. He also continued his interest in computational analysis of cancer drivers by co-developing GECCO, an algorithm for the identification of noncoding mutations driving gene expression in pancreatic cancer (Feigin and Garvin, et al., Nature Genetics, 2017). Mike's lab has two main areas of interest: 1) alternative polyadenylation as a targetable driver of pancreatic cancer, and 2) dysregulation of the pancreatic tumor microenvironment by commonly prescribed anti-anxiety drugs." Dr. Michael Feigin on the web Roswell Park Feigin Lab Google Scholar LinkedIn Twitter Dr. GPCR AI Summary AI-generated content may be inaccurate or misleading. Always check for accuracy. Quick recap Yamina and Mike engaged in a conversation about their scientific research experiences. Mike shared his journey from his Ph.D. struggles to his current role as a professor, emphasizing the importance of resilience and creativity. They also discussed his research on cell polarity and its role in cancer progression, his work on G-protein coupled receptors (GPCRs) in breast cancer, and his interest in pancreatic cancer. The discussion also covered the challenges they face in studying GPCRs due to their low expression levels and the difficulty of localizing these receptors in tissues. Next steps • Mike will consider using Twitter to post job positions in his lab. Summary Science Roles and Resilience Yamina and Mike had a conversation about their roles and experiences in the field of science. Yamina introduced herself and Mike shared his educational background and his journey to becoming a professor. Mike also spoke about his initial struggles during his Ph.D., such as a difficult model system and a lack of experimental results. He explained that he overcame these challenges by reading extensively and contemplating alternative plans. The conversation also highlighted the importance of resilience and creativity in scientific research. Science Journey and Postdoc Decision Mike discussed his journey into science and his decision to pursue a postdoc at Cold Spring Harbor. He shared that his interest in science originated from a young age and his desire to gain more knowledge about cancer biology led him to transition into using mouse models. Yamina asked about his move from in vitro to in vivo work, and Mike explained that he wanted to use better models to understand cancer signaling pathways. They also shared their personal experiences and interest in the field of biology. Towards the end, Mike mentioned that he stayed at Cold Spring Harbor even after his mentor left for Toronto. Mike's Research on Cell Polarity and GPCRs in Cancer Mike shared his research on cell polarity and its role in cancer progression, particularly focusing on the potential of disrupted cell polarity as a driver of tumorigenesis. He also discussed his work on G-protein coupled receptors (GPCRs) in breast cancer, identifying GPR161 as a potential drug target due to its high expression in triple negative breast cancer. Mike then transitioned to pancreatic cancer, questioning why genes are dysregulated in cancer, which led him to explore different aspects of gene regulation and its relation to cancer progression. Yamina acknowledged the difficulty in identifying GPCRs expressed in cancer cells but not in normal ones, and commended Mike's innovative approach to the question. Career Trajectory and Faculty Position Yamina and Mike discussed Mike's career trajectory and his decision to pursue a faculty position. Mike expressed his initial reluctance due to a lack of confidence and fear of not being ready. However, he decided to undertake another postdoc to gain more experience and confidence. He also highlighted the importance of publishing strong papers and having a clear vision for his lab. Yamina emphasized the importance of thorough preparation and planning before applying for faculty positions. They also discussed the challenges of the two-body problem, where both partners need to find suitable positions. Mike shared his strategy of developing preliminary projects and gathering data to strengthen his application. Teamwork and Flexibility in Scientific Research Mike shared about his recent promotion and the way he has managed his team, encouraging them to come up with their own ideas and then guiding them. Yamina congratulated Mike on his promotion and discussed the importance of flexibility in scientific research, even when starting with a clear plan. Mike also mentioned how his team collaborates closely, with weekly roundtable discussions where everyone shares their progress and issues. The conversation ended with Yamina expressing interest in learning more about Mike's two main research areas in his lab. GPCR Targeted Drugs and Gene Regulation in Cancer Cells Mike presented research on the effect of GPCR-targeted drugs on cancer-associated fibroblasts and discussed their work on gene regulation in fibroblasts. He highlighted their interest in non-coding mutations in promoters and the 3'UTR region important for gene regulation. Mike also shared about a drug that targets an enzyme involved in mRNA cleaving, which has been found to stop cancer cells from growing and invading. He also discussed the impact of disrupting histone processing on rapidly proliferating cells, such as cancer cells, and suggested a therapeutic index for a drug called JTE-6.7. Yamina asked about the typical role of the enzyme and the challenges in delivering a molecule to target this enzyme and only cancer cells. Cytokine Inhibition, Collaboration, and Anti-Anxiety Drug Research Mike discussed the ongoing research on a drug that inhibits cytokine synthesis, its potential in killing cancer cells, and the team's efforts to understand its resistance mechanisms. He also touched upon a collaboration with Todd Ricky's group at UPenn to explore the GPCR side of the lab, which led to the discovery of potential tumor suppressors and oncogenes in melanoma. Furthermore, Mike mentioned a qualifying exam where students proposed new projects, highlighting Abby Cornwell's project on the effects of anti-anxiety drugs on pancreatic cancer patients, and the team's research on the potential issues with certain anti-anxiety drugs. The team found that these drugs could interact with GPR68, which is highly expressed in cancer-associated fibroblasts and is crucial for their function, leading to complications in cancer patients. The team is now examining other anti-anxiety drugs and common patient medications in the context of pancreatic cancer. GPCRs and Cancer Immune Modulation Yamina and Mike had a discussion about their research on GPCRs, specifically focusing on GPR68 and its role in the tumor microenvironment. They also touched upon the potential of GPCR modulation in stimulating the immune system to fight cancer. Mike shared his team's current focus on alprazolam, an anti-anxiety medication that has unexpected effects in the tumor microenvironment. They also discussed the challenges they face in studying GPCRs due to their low expression levels and the difficulty of localizing these receptors in tissues. Mike expressed a need for better tools to study GPCR localization in tissues. Scientific Journey and Drug Discovery Challenges Mike shared significant moments in his scientific journey, including the discovery of RGS proteins and its impact on his research approach. He also discussed his experiments and discoveries about GPR161 in mammary epithelial cells, the effect of alprazolam on tumors, and the potential dangers of drug interactions. Yamina proposed further exploration of dosage and length of treatment in a mouse model and suggested using a biosensor-based assay to examine dose-response curves. The conversation highlighted the complexities and challenges of drug prescription and the potential for alternative treatments. Science Journeys and Career Advice Yamina and Mike discussed their experiences in the field of science. Mike advised junior scientists to focus on projects they are passionate about, emphasizing that ownership and full investment in a project can make dealing with challenges easier. Yamina shared her personal journey, describing how she took her project in a different direction and felt a sense of ownership. Mike reflected on his early years as a postdoc, admitting that he lacked focus and didn't see the direct impact of his work on patients. He highlighted the importance of re-evaluating one's work and its potential implications. Towards the end, Yamina asked about job opportunities in Mike's lab, to which Mike responded that potential candidates can find him on Twitter. 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 >>

Catherine Demery shares how she found clarity and purpose in academic opioid research. From her early doubts to designing preclinical models of fentanyl and xylazine overdose, she reflects on staying in academia, building translational experiments, and using real-world data to drive impactful science in the GPCR research community. << Back to podcast list Strategic Partner(s) Xylazine, Fentanyl, and the Fight for Breath with Catherine Demery Two drugs. Two different mechanisms. One deadly outcome. Fentanyl and xylazine are pushing the opioid crisis into dangerous new territory, and Catherine Demery is on the front lines of the science trying to stop it. In this gripping conversation, Catherine, a PhD candidate at the University of Michigan, shares how personal loss and an unconventional career path—industry chemist, NIH researcher, and now GPCR pharmacologist—led her to investigate how these drugs shut down breathing in different ways. Her research combines cutting-edge GPCR signaling studies with real-time public health data from Michigan’s Red Project, revealing how fentanyl slows inhalation, xylazine prolongs exhalation, and together they drop heart rate to dangerous lows. And while users aren’t asking for xylazine, dealers are lacing it into the supply—driving overdose deaths higher. Why This Matters Fentanyl : Potent synthetic opioid that decreases inhalation rate. Xylazine : Veterinary sedative that prolongs exhalation and induces bradycardia—acting through alpha-2 adrenergic, not opioid, receptors. The Combo : Not just additive—lethal. Street Data : Xylazine-laced fentanyl in Michigan has jumped 30–60% in recent years. What You’ll Learn in This Episode How industry lab experience builds the discipline needed for academic research. Why xylazine is an emerging overdose threat and how it differs mechanistically from opioids. The methods used to measure respiratory depression in live models. How loss and lived experience can sharpen scientific focus. The role of public health programs in informing lab research. How GPCR pharmacology connects molecular insights to real-world interventions. Who Should Listen This episode is especially relevant for: GPCR drug discovery scientists Respiratory pharmacologists Addiction researchers Public health professionals Early-career scientists navigating non-linear paths About Catherine Demery Catherine Demery didn’t set out to be on the front lines of the opioid crisis. After earning her undergraduate degree in biochemistry from the University of Michigan, she deferred pharmacy school, unsure if that path felt right. Instead, she went hands-on—working as an analytical chemist in a GLP/GMP-regulated CRO, where precision and discipline became second nature. That led her to a master’s in pharmacogenomics at Manchester University, igniting her fascination with how genetics and drugs interact. Her next stop: the NIH, studying the immunology of pregnancy. But loss has a way of sharpening focus—friends lost to overdose brought the opioid epidemic into painful clarity. Catherine decided to act where she could make the biggest difference: in the lab. Today, as a PhD candidate in the labs of Dr. John Traynor and Dr. Jessica Anand at the University of Michigan, Catherine investigates how fentanyl and xylazine shut down breathing through different mechanisms—work that blends receptor pharmacology, preclinical models, and public health data to tackle one of the most urgent challenges in addiction science. Catherine Demery on the web LinkedIn Google Scholar University of Michigan 🎧 Listen now and see how one scientist is turning molecules into a mission, bridging the gap between receptor pharmacology and the urgent fight to save lives in the opioid epidemic. 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. Nicolas Gilles About Dr. Nicolas Gilles "Dr. Nicolas Gilles is an expert in the study of animal toxins. He is pioneering the investigation of animal toxins acting on GPCRs, the largest therapeutic target class. His strongest expertise lies in therapeutic target identification and all the steps from venom manipulations, to in vivo validation. When the pharmacological properties of these new ligands are deemed exceptional, a lead optimization is realized and its therapeutic development initiates through a dedicated start-up." Dr. Nicolas Gilles on the web Google Scholar 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 >>

<< Back to podcast list Strategic Partner(s) Dr. Katarina Nemec About Dr. Katarina Nemec " I am a pharmacist with an interest in systems pharmacology and precision medicine. Since my undergraduate studies, I have been engaged in researching molecular mechanisms that govern human (patho-)physiology and their interplay with drugs. I aim to discover new therapeutic approaches, and druggable molecules or refine canonical drug targets to create drugs with fewer adverse effects. I studied Pharmacy at the University in Ljubljana, Slovenia, and at the University of Bonn, Germany, working initially on the role of prostaglandin receptor EP4 in chronic lymphocytic leukemia. During my PhD studies in Martin Lohse lab at the Max Delbrueck Center in Berlin, I consolidated my knowledge of GPCRs pharmacology while performing various cell-based experiments to understand the binding, activation, and signaling of therapeutically relevant GPCRs. In addition, I generated various optical biosensors based on fluorescence or bioluminescence resonance energy transfer technologies (FRET, BRET) that were used for functional screens with state-of-the-art microscopy and high throughput screening to explain novel ways of GPCR modulation. I am continuing with the development of advanced screening approaches in the Madan Babu lab to progress in the understanding of spatiotemporal regulation of biased GPCR activation and signaling. I want to combine experimental approaches with data-driven discovery and adopt data science methodology to tackle relevant scientific questions on the systems pharmacology level. " Dr. Katarina Nemec on the web Babu Lab ResearchGate Google Scholar ORCID 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 >>