<< Back to podcast list Strategic Partner(s) Dr. Lukas Grätz About Dr. Lukas Grätz "After a BSc in biology and a MSc in bioinformatics, I have been working in David Gloriam's group as a bioinformatician. My initial focus was on creating an automated chimeric homology modeling pipeline for GPCRs and since have branched out to multiple areas of GPCR research such as sequence alignments, generic numbering systems, structure data, G protein and arrestin coupling and more. As a developer, and more recently the lead developer of GPCRdb my day-to-day work centers around the maintenance and resource/tool development of GPCRdb and its sister databases. I am also affiliated with György Keserű's group at the RCNS in Hungary. I lived in Denmark, Poland, now I live in Hungary. I am married, I have two daughters. In my free time I like to play the guitar, sing and play board games. " Dr. Lukas Grätz on the web Karolinska Institutet ResearchGate PubMed Dr. GPCR Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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 Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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 >>

Alessandro Nicoli shares how he models olfactory GPCRs with AlphaFold, mentors students, and builds science from scratch in a new lab. A fresh look at computational GPCR research. << Back to podcast list Strategic Partner(s) Smells Like GPCR Spirit: Cracking Olfactory Codes with Alessandro Nicoli The Accidental Path to Science Alessandro Nicoli didn’t grow up knowing he’d be a scientist. Like many, his path to GPCR research wasn’t linear—it evolved through academic exploration and mentorship. “I think I don’t have a linear trajectory… the beauty of seeing molecule design and reactions—thinking you can create molecules—was really exciting.” – Alessandro Nicoli He studied pharmaceutical chemistry in Padua, where his fascination with molecular design first took shape. But it wasn’t until meeting an inspiring professor, Prof. Moro, that he truly saw how molecules could go beyond the bench and interact with biology in powerful ways. The Moment Chemistry Met Biology Nicoli’s turning point came when he realized that molecules weren’t static—they could act , bind , and modulate biological targets. “It was not just a molecule—it was a partner that goes to interact with something else… a protein, DNA, RNA. That opened up a new world.” – Alessandro Nicoli That early spark led him to discover the role of medicinal chemistry and, eventually, molecular modeling. For Nicoli, chemistry became more than reactions—it became a bridge to biological insight. Falling for Computational Chemistry The "second academic love" arrived during his master’s thesis, where Nicoli dove into computational chemistry. “I got to know computational chemistry through a project on BCL2 proteins and drug discovery… I was in love with the topic.” – Alessandro Nicoli Working on docking and NMR studies for cancer-related proteins, he discovered the power of simulation in revealing molecular interactions. That experience convinced him to pursue a PhD and deepen his computational skills—eventually leading him to GPCRs. Finding the Right Mentor and Lab A birthday email changed everything. Professor Moro forwarded a PhD opening from Prof. Antonella Di Pizio’s lab in Munich. It felt serendipitous—and it was. “We had a super match… and after a month, I was already in Germany. I was her first PhD student.” – Alessandro Nicoli Starting from scratch in a young lab wasn’t easy, but it created a unique bond between PI and student. Nicoli thrived in this setting—helping shape the lab and its direction, particularly in computational studies of olfactory GPCRs . GPCRs, Receptors of Infinite Variety When asked about his favorite GPCR, Nicoli refused to pick. “Let’s embrace the challenge to study all of them… they’re unique in how they bind ligands, how selective they are.” – Alessandro Nicoli He emphasized that olfactory receptors , while underexplored, present an incredible challenge. With hundreds of subtypes and very few known ligands, the structure–function relationships remain largely mysterious—and incredibly exciting for a computational chemist. AlphaFold: A Turning Point in GPCR Research When Nicoli began his PhD, AlphaFold hadn’t yet revolutionized the field. But once released, it changed everything. “AlphaFold gave us a face to those proteins… now we have 400 models to start with.” – Alessandro Nicoli He explained how AlphaFold’s predictions, surprisingly close to experimental structures, provided a powerful starting point for docking, dynamics, and ligand design—especially for receptors previously “invisible” to structural biology. Modeling the Invisible: Olfactory Receptors Nicoli’s work centers on predicting ligand binding and receptor behavior for olfactory GPCRs. “The main challenge was: how do we get a face for these proteins when we don’t have ligands?” – Alessandro Nicoli He shared a detailed case study of working on a specific odorant receptor (R5VK1), where they leveraged known active/inactive ligands to validate models through iterative refinement , molecular docking , and mutagenesis-guided optimization . The goal? Build predictive models to discover new ligands . Why Molecular Dynamics Matters For Nicoli, molecular dynamics is more than simulation—it’s how we watch biology move . “You simulate over time… see how receptors move in physiological conditions, with water, membranes, ligands.” – Alessandro Nicoli He emphasized that MD allows researchers to observe allosteric changes , mutation effects , and even ligand entry/exit paths , offering dynamic insights that static structures cannot. It’s a critical complement to experimental work. From Researcher to Mentor: Growing Together Outside his research, Nicoli mentors students, manages interns, and even lectures. Balancing this with a PhD isn't easy, but it’s deeply rewarding. “You have people that rely on you… but you grow together, and that’s the most powerful thing.” – Alessandro Nicoli He reflected on learning to delegate—how hard it was initially to hand over tasks—but how vital it is for team science. He now sees mentoring as a way to shape the next generation while evolving himself as a scientist. Advice, Tools, and the Future of GPCR Research Nicoli offered advice to wet-lab scientists curious about computational work: Start with passion. Learn Python. Explore online resources like “Talktorials.” “We’re living in a golden era for computational chemistry… the tools are out there. You just need the motivation to explore.” – Alessandro Nicoli As for what’s next? More structures, better tools, and deeper insights into the elegant, complex world of GPCRs. He sees a future where wet and dry labs converge , and where computational methods are fully integrated into GPCR drug discovery pipelines. Key Takeaway Alessandro Nicoli’s journey is a compelling example of how computational chemistry can unlock new frontiers in GPCR research , especially in complex areas like olfactory receptors. By bridging structural prediction, molecular dynamics, and ligand discovery, his work not only deciphers biological mysteries but also inspires a new generation of scientists to think computationally. About Alessandro Nicoli Alessandro Nicoli is currently a PhD student in the Molecular Modeling group led by Prof. Dr. Antonella Di Pizio at the Leibniz Institute for Food Systems Biology at the Technical University of Munich (Germany). He obtained an MSc degree in Chemistry and Pharmaceutical Technology from the University of Padua (Italy). His training and passion for computational chemistry started in 2019 during his time at the Molecular Modeling Section (MMS) under the supervision of Prof. Stefano Moro, where he worked on integrated Nuclear magnetic resonance (NMR) and computational modeling strategies to target the antiapoptotic BCL-2 protein family, key regulators of cell survival, using small molecules. He then moved to Germany in 2019 to pursue his PhD. His research focuses on a group of 400 transmembrane proteins known as olfactory receptors, which mediate the sense of smell. Beyond the olfactory epithelium, these receptors are expressed in various tissues, where they play important but not yet fully understood roles in various physiological and pathological processes. Despite their relevance, they remain understudied due to the limited knowledge of their ligands and the lack of experimental structures. Alessandro PhD work aims to fill these gaps by leveraging computational structure-based tools and develop specific protocols to accelerate OR ligand discovery and improve our understanding of olfactory function at the molecular level. Alessandro Nicoli on the web Leibniz Institute for Food Systems Biology at the Technical University of Munich Technical University of Munich Google Scholar Pubmed ORCID ResearchGate X Bluesky Github Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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) Robert Laprairie About Dr. Robert Laprairie Dr. Robert Laprairie is an Associate Professor and the Saskatchewan Research Chair in Drug Discovery and Development in the College of Pharmacy and Nutrition at the University of Saskatchewan. The focus of his research is the molecular pharmacology of cannabinoids and cannabinoid receptors. He was the 2018 and 2021 recipient of the Young Investigator of the Year Awards from the British Pharmacological Society and International Cannabinoid Research Society (ICRS), respectively. In 2019 he became the Director of Education for the Canadian Consortium for the Investigation of Cannabinoids (CCIC) and now also serves as the organization’s President. Dr. Robert Laprairie on the web University of Saskatchewan Twitter Instagram ResearchGate Google Scholar Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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 1 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. Jeffrey Benovic (1985) Dr. Michel Bouvier (1985) Dr. Kathleen Caron - Co-host- (1970) Dr. Richard Cerione (1985) Dr. Brian Kolbilka (1987) Dr. Frederik Leeb-Lundberg (1984) Dr. Robert Lefkowitz (1973) Dr. Lee Limbird (1973) Dr. David Sibley (1988) Memories our panelists shared with us https://video.wixstatic.com/video/93ce84_92e3a06139244357b0823e3ecc294e27/1080p/mp4/file.mp4 Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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. Sudarshan Rajagopal About Dr. Sudarshan Rajagopal Dr. Sudarshan Rajagopal obtained his B.S. in Chemistry from The University of Chicago in 1998. He subsequently enrolled in the Medical Scientist Training Program at The University of Chicago. During his doctoral work in the lab of Prof. Keith Moffat, he studied the structural mechanisms of bacterial photoreceptors using time-resolved Laue crystallography. He was awarded his Ph.D. in 2004 and his MD in 2006. He then joined the Internal Medicine Residency training program at Duke University Medical Center. During his Cardiology fellowship, he trained in the lab of Dr. Robert J. Lefkowitz , where his research focused on biased agonism, with the development of approaches to quantify ligand bias and the identification of beta-arrestin-biased receptors. After completing his training in clinical cardiology, he started as an Assistant Professor of Medicine at Duke University School of Medicine. The main focus of his lab’s research is on the mechanisms underlying biased agonism at chemokine receptors and how that contributes to inflammation. The chemokine system is relatively unique in having multiple receptors and multiple ligands that display considerable promiscuity for one another. His group and others have shown that many of these ligands act as biased agonists for the same receptor. His lab is also interested in identifying novel signal transduction mechanisms of GPCRs, such as the formation of complexes between G proteins and beta-arrestins. His clinical focus is on pulmonary arterial hypertension, a disease of the pulmonary arterioles that causes right heart failure, and he serves as co-director of the Duke Pulmonary Vascular Disease Center. Dr. Sudarshan Rajagopal on the web LinkedIn Website Google Scholar LinkedIn Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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. Ilana Kotliar About Dr. Ilana Kotliar "Ilana Kotliar is a postdoctoral associate in the lab of Tom Sakmar at The Rockefeller University, where she just recently defended her PhD thesis. Ilana uses chemical biology-based methods to study the regulation and protein-protein interactions of GPCRs and a small family of accessory proteins called RAMPs. Ilana’s research is multi-disciplinary and involves a close collaboration with proteomics experts at The Science for Life Laboratory in Sweden. She is a recipient of the prestigious Women in Entrepreneurship Award, an NIH T32 Training Grant, and two Nicholson Fellowships. Outside of the lab, Ilana is a leader within her community, spearheading several outreach initiatives including a global mentoring initiative that matches graduate student mentors to PhD applicants. Ilana graduated Summa cum laude from Cornell University, where she studied Chemistry and Chemical Biology and was recognized as a Merrill Presidential Scholar." Dr. Ilana Kotliar on the web Google Scholar LinkedIn Twitter Dr. GPCR Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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. Arthur Christopoulos About Dr. Arthur Christopoulos " Arthur Christopoulos is the Professor of Analytical Pharmacology and the Dean of the Faculty of Pharmacy & Pharmaceutical Sciences, Monash University, Australia. His research focuses on novel paradigms of drug action at GPCRs, particularly allosteric modulation and biased agonism, and incorporates computational and mathematical modelling, structural and chemical biology, molecular and cellular pharmacology, medicinal chemistry, and preclinical models of behaviour and disease. His work has been applied to studies encompassing neurological and psychiatric disorders, cardiovascular disease, obesity, diabetes, chronic pain and addiction. He has received substantial, long-term support from international and national competitive, charitable and commercial sources, as well as being academic co-founder of three GPCR-focussed biotechnology companies. Professor Christopoulos has over 360 publications, including in leading international journals such as Nature,Science and Cell, and has delivered over 180 invited presentations. He has served on the Editorial Board of 8 international journals and was a Councillor of the International Union of Basic and Clinical Pharmacology (IUPHAR). He has also been the recipient of multiple awards, including the John J. Abel Award and the Goodman and Gilman Award from the American Society for Pharmacology and Experimental Therapeutics; the Rand Medal from the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists; the British Pharmacological Society’s Gaddum Memorial Award; the IUPHAR Sir James Black Analytical Pharmacology Lecturer; the GSK Award for Research Excellence and a Doctor of Laws (Honoris Causa) from the University of Athens. Since 2014, Clarivate Analytics have annually named him a Highly Cited Researcher in ‘Pharmacology & Toxicology’, and in 2021 also named him a Highly Cited Researcher in the additional category of ‘Biology & Biochemistry’. In 2017, he was elected a Fellow of the Australian Academy of Health and Medical Sciences, in 2018 as a Fellow of the British Pharmacological Society, and in 2021 he was elected a Fellow of the Australian Academy of Science for his seminal contributions to drug discovery. In 2023, he was elected a Fellow of the Pharmaceutical Society of Australia. " Dr. Arthur Christopoulos on the web Monash University Wikipedia Google Scholar LinkedIn Dr. GPCR AI Summary AI-generated content may be inaccurate or misleading. Always check for accuracy. Quick recap Yamina and Arthur from Monash University discussed Arthur's career journey, the importance of hard work, failure, and differentiation in academic and personal lives, and the value of international conferences. They also explored the significance of translating fundamental discoveries into clinical applications, the potential of new drugs, and the unique challenges within universities. Additionally, they discussed the importance of hiring based on differentiation, impact, and interest, the need for workforce development, and the potential of involving junior scientists and postdocs in their podcast. Lastly, they touched upon the global challenges of healthcare workforce growth, climate change, and emerging psychiatric disorders, as well as the importance of recording lectures and making pre-lesson materials available to students. Next steps - Yamina will share notes about PRISM and presentability with Arthur. - Arthur will share the story of PRISM's development and its impact on the field with Yamina. - Yamina will send an invite for a follow-up meeting with Arthur next Saturday at 9 PM. - Arthur and Yamina will prepare for the next meeting, focusing on the concept of biased agonism and discussing Dr. GPCR and the charity status. - Yamina will attempt to book Denise for a future podcast episode. Summary Arthur's Career Journey and Transition to Dean Yamina introduced Arthur to her team and discussed the use of a particular tool for meeting summaries. Arthur shared his career journey from pharmacy to becoming a professor, highlighting the influence of his mentors and the importance of his postdoctoral experience. They discussed the value of hard work, failure, and the significance of differentiation in their personal and academic lives. Towards the end, they focused on Arthur's transition to become Dean and his decision to move from Australia to the United States for a postdoctoral position. Postdoctoral Position, Scientific Dynamics, and New Drug Targets Arthur shared his decision to undertake a postdoctoral position with Nigel Bird's lab in the UK and his experiences of meeting influential figures during his time in the US. He and Yamina discussed the importance of preserving original work, the value of international conferences, and the dynamics between junior and senior scientists in a research environment. They also shared their admiration for the work of a mutual friend and discussed the history of muscarinic receptors, specifically focusing on the role of a compound that Arthur received from Fred. Lastly, they discussed the progress of new drugs targeting specific receptors for various diseases, with Arthur sharing insights on Eli Lilly's compound, Xanomeline, and the potential of M4 PAM for psychosis. Collaborative Research and Translational Approach Arthur and Yamina from Monash University discussed their collaborative approach to scientific research, emphasizing the benefits of combining their complementary skills and interests. They shared their unconventional approaches to research, including the creation of a critical mass of GPCR researchers in Australia and the initiation of a successful series of conferences. They also discussed the relocation of some university labs to facilitate collaboration and overcome the siloed department structure. Additionally, they explored the unique culture and structure of their Institute, highlighting its translational approach to research and its capacity to translate research into therapeutic commercialization. Lastly, Arthur shared three significant moments that shaped his career, including the evolution and impact of analytical pharmacology, particularly highlighting the role of Prism, a data analysis tool. Podcast Format, Team Culture, and Science Yamina and Arthur concluded their discussion and decided to take a short break. They talked about the format and length of their podcast, their professional interests, and their recent successful bid to bring Moderna to their university. They also explored the idea of starting a similar talk show format to 'Between Two Ferns', the importance of maintaining team culture, and the potential health issues among well-known scientists. Lastly, they discussed the growth and development of the Monash Institute of Pharmaceutical Sciences, the importance of knowing when to let go in scientific experiments, and the idea of a panel for building and incubating companies. Arthur's Pandemic Journey and Global Challenges Yamina and Arthur discussed Arthur's experiences during the Covid-19 pandemic, his journey as a research fellow in Australia, and his transition to the role of Dean. Arthur shared his insights into the unique grant funding system in Australia, the importance of impact in research, and the challenges of balancing administrative responsibilities with scientific pursuits. He also reflected on his personal health struggles, the growth of his university, and the faculty's successful response to the Covid crisis. The conversation also touched upon Arthur's career decisions, his scientific achievements, and the importance of learning from mistakes and self-confidence. Lastly, they discussed the global challenges of healthcare workforce growth, climate change, and emerging psychiatric disorders, as well as the importance of recording lectures and having pre-lesson materials available to students. Translating Discovery Into Clinical Application Arthur and Yamina discussed the importance of translating fundamental discoveries into clinical applications in their research, highlighting the unique opportunities presented by their location and partnerships with other institutions. They stressed the necessity of making their research goals clearer, avoiding replication, and adopting a more assertive approach in grant applications. They also emphasized the significance of fundamental discoveries, the role of biotech, and the need for efficiency and process development in university systems. The conversation highlighted ongoing challenges within universities, including resistance to change and the need to communicate expectations and protect established cultures. Hiring Process, Collaboration, and Education-Focused Initiatives Arthur emphasized the importance of differentiation, impact, and interest in their hiring process and fostering a culture of collaboration. He shared his vision of breaking down barriers and promoting education-focused initiatives, encouraging his team to be innovative and apply their skills to education. Yamina expressed a desire to learn from successful leaders and the importance of recognizing talent and matching it with the needs of a particular project. They also discussed the disruption within the pharmaceutical sector, the importance of workforce development, and the need for maintaining a healthy work-life balance. Lastly, they deliberated on involving junior scientists and postdocs in their podcast and the possibility of writing a book about their experiences in academia. Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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) Brian Shoichet About Dr. Brian Shoichet BSc in Chemistry from MIT, Ph.D. with Tack Kuntz at UCSF; Postdoc with Brian Matthews in protein stability-activity tradeoffs, crystallography; started my independent lab at Northwestern University Medical School (1996) was recruited back to UCSF in 2003. Dr. Brian Shoichet on the web Google Scholar Shoichet Lab Twitter Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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) Gáspár Pándy-Szekeres About Gáspár Pándy-Szekeres " After a BSc in biology and a MSc in bioinformatics, I have been working in David Gloriam's group as a bioinformatician. My initial focus was on creating an automated chimeric homology modeling pipeline for GPCRs and since have branched out to multiple areas of GPCR research such as sequence alignments, generic numbering systems, structure data, G protein and arrestin coupling and more. As a developer, and more recently the lead developer of GPCRdb my day-to-day work centers around the maintenance and resource/tool development of GPCRdb and its sister databases. I am also affiliated with György Keserű's group at the RCNS in Hungary. I lived in Denmark, Poland, now I live in Hungary. I am married, I have two daughters. In my free time I like to play the guitar, sing and play board games. " Gáspár Pándy-Szekeres on the web LinkedIn University of Copenhagen ResearchGate Twitter Dr. GPCR Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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 >>

In this short resilience conversation, Dr. Graciela Pineyro shares what a forced lab shutdown taught her about prioritization, remote lab meetings, and running a research program across closed borders. << Back to podcast list Strategic Partner(s) Graciela Pineyro: Resilience, Lab Life, and the Zoom Effect Research doesn't pause neatly. In March 2020, Dr. Graciela Pineyro — a principal investigator at CHU Sainte-Justine in Montreal studying GPCR signaling — watched her lab close from one day to the next. This short resilience conversation, part of a Dr. GPCR Podcast series capturing the realities of scientific life, returns to Dr. Pineyro several months into the shutdown to hear what she learned. The discussion moves across three overlapping questions: how a forced pause reshapes scientific prioritization, how remote lab meetings alter who speaks up and why, and what it costs a scientist personally to keep a lab running across a closed international border. For Dr. Pineyro, whose husband remained in Uruguay for the duration of the shutdown, the scientific work and the human cost were never separate conversations. What emerges is a quiet argument that the structural shifts the pandemic forced — project planning in self-contained blocks, flatter meeting dynamics, planned reflection time — may deserve to survive the return to the bench. About the Guest Dr. Graciela Pineyro is a principal investigator at CHU Sainte-Justine in Montreal, where her research group works on GPCR signaling. She is a returning guest of the Dr. GPCR Podcast; her earlier episode covers her scientific profile in depth, including her research trajectory, laboratory focus, and contributions to the field. This resilience conversation captures her voice not as a researcher presenting results, but as a PI speaking candidly about how her program is navigating a moment no one planned for. Scientific Themes of the Conversation Forced pause as a prioritization tool — How closure reveals what a lab would otherwise never stop to question. The democratizing effect of remote meetings — Why some lab members speak more freely from home than they ever did in person. Experimental planning under uncertainty — Structuring projects into self-contained blocks so a lab can survive iterative shutdowns. The personal geography of modern science — What it costs a scientist when the research program and the family are in different countries. Civic responsibility in returning to the bench — Deconfining a research center slowly, with planning for possible return to closure. Key Insights from the Conversation The pause was never just a pause. Dr. Pineyro frames the shutdown not as lost time but as a rare moment of recul — the French word for a step back that allows for perspective. She talks about finally being able to ask which projects deserved to be finished first, second, third. The question was always there; the pause was what forced it to be answered. Zoom did not flatten the lab. It flattened the hierarchy of who gets heard. The most striking observation in the conversation: lab members who rarely spoke up during in-person meetings began contributing more on Zoom. Dr. Pineyro notes she isn't sure why — something about speaking from home, something about reduced interpersonal threat. But the finding is sharp enough to take seriously when in-person dynamics return. Planning in blocks is a form of resilience. The lab restructured projects into discrete, self-contained units — each one designed so that if the research center closed again, the team would still have something to analyze, something to write. This is operational wisdom that long outlives the pandemic. The personal cost doesn't stay outside the lab. Dr. Pineyro speaks openly about her husband being stuck in Uruguay since March, missing their planned reunion, hoping for Christmas. She does not separate this from the scientific conversation — and the listener shouldn't either. Running a lab during the pandemic was rarely just a scientific problem. Returning to the bench is a decision, not a default. The research center was deconfining at 20% capacity the week of the recording. Dr. Pineyro frames reopening as something her team is taking "civically with responsibility and a grain of salt" — acknowledging that back-and-forth closures may be the new baseline. That framing, made months before it became the standard narrative, is worth noticing. Some pandemic-era practices deserve to survive. The implicit argument threaded through the whole conversation: the structural shifts forced by the shutdown — planned reflection, remote meeting inclusion, block-based project design — may be worth keeping. Not because the pandemic was good for science, but because normal lab life had quietly suppressed some of the things the pause made visible. Episode Timeline Timestamps were generated using AI for readability. 00:00 Introduction and 2020 Summit announcement 01:45 Welcoming a returning guest 02:02 How COVID reshaped the lab and the personal cost 03:30 Using forced pause for prioritization 04:10 Planning experiments in self-contained blocks 04:47 The Zoom effect — quieter voices speaking up 05:49 Closing reflections 06:01 Outro Selected Quotes "One day we were doing experiments, and the next we had to close. We have to go back now and start from scratch." "Zoom democratizes the world. People that usually do not speak so much in the lab meetings were speaking a little bit more through Zoom." "We are sort of thinking in advancing our projects in sort of blocks, closing some questions very tightly. So if we are sent back home, at least we have something to work on." "We are all prepared to take this civically with responsibility and also with a grain of salt, knowing that we might have to be going back and forth for a while before everything goes back to normal." About this episode: Dr. Graciela Pineyro is a professor of pharmacology at the department of pharmacology and physiology of the University of Montreal. She has done extensive work on the molecular pharmacology of opioid receptors and is currently focusing on the pharmacology of cannabinoids in the context of pain. We chatted about how the current pandemic has affected her personally and professionally. 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 Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Dr. Jean-Philippe Pin About Dr. Jean-Philippe Pin Jean-Philippe Pin participated in the discovery of metabotropic glutamate receptors. Since then, he has been studying the allosteric modulation and activation mechanism of this family of G protein-coupled receptors using innovative approaches, including biosensors, cryo-EM, photoswitchable ligands, and nanobodies as pharmacological tools and potential therapeutic agents. His studies led to new concepts in the GPCR field, such as the activation of cell surface receptors by intracellular proteins; the regulation of GPCRs by both negative and positive allosteric modulators, and the asymmetric functioning of GPCR dimers. Dr. Jean-Philippe Pin on the web LinkedIn ResearchGate CNRS Fondation Bettencourt Schueller FRC Neurodon Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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. JoAnn Trejo About Dr. JoAnn Trejo Dr. JoAnn Trejo earned her Ph.D. at UC San Diego. She completed her postdoctoral fellowship at UC San Francisco under the guidance of Professor Shaun Coughlin where she worked on the newly discovered protease-activated GPCRs. Dr. Trejo joined the faculty in the Department of Pharmacology at the University of North Carolina in 2000 and then moved to UC San Diego School Medicine, Department of Pharmacology in 2008, where she quickly rose through the ranks to tenured professor in 2012. In 2014, she was appointed Vice-Chair of the Department of Pharmacology. The long-term goal of Dr. Trejo’s research program is to gain a thorough and mechanistic understanding of processes that control cell signaling by protease-activated receptors (PARs) and the impact on vascular inflammation and cancer progression. PARs are GPCRs that are activated through an atypical irreversible proteolytic mechanism. The precise control of PAR signaling is critical for proper temporal and spatial dynamics of signaling and appropriate cellular responses. Discovering new aspects of PAR signaling is important for increasing the fundamental knowledge of GPCR biology and for the identification of drug targets and future drug development. Dr. Trejo’s research has focused on PAR1, which has important functions in hemostasis, thrombosis, inflammation, and cancer and is an important drug target. She has made numerous important discoveries related to the mechanisms that control PAR1 signaling and closely related family members and published extensively on this topic. Dr. Trejo has been continuously funded by the NIH for >20 years and was a recipient of the prestigious American Heart Association Established Investigator Award. Her laboratory is the recognized expert on protease-activated receptors, particularly PAR1, and over the years she has discovered novel aspects of GPCR biology, acquired critical expertise, and rigorous approaches to examine PAR1 function using human cultured cells and mouse models. Dr. Trejo has presented her studies at 52 national/international meetings and 66 academic seminars across the U.S. Dr. JoAnn Trejo on the web UC San Diego Trejo Lab Wikipedia LinkedIn Google Scholar Orcid Twitter UC San Diego School of Medicine Researchgate Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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. Shivani Sachdev About Dr. Shivani Sachdev "Dr. Sachdev is an early career researcher in the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health. Her research centers on developing nanobody-ligand conjugates to target GPCRs, with a focus on receptors relevant for treating osteoporosis, diabetes, and pain. She received her undergraduate degree in Biotechnology from KIIT University in India. She subsequently joined Professor Mark Connor's laboratory at Macquarie University in Australia. Dr. Sachdev pursued Ph.D. in the same lab where she investigated the molecular pharmacology of cannabinoid receptors. She is also very active within the pharmacology community and currently serves on the editorial board of the British Journal of Pharmacology. Given her expertise in GPCR pharmacology and scientific communication, she is poised to make valuable contributions to the field and expand our understanding of GPCR signaling." Dr. Shivani Sachdev on the web NIDDK ReseachGate Google Scholar LinkedIn Twitter Dr. GPCR Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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. Marta Filizola About Dr. Marta Filizola Dr. Marta Filizola is the Sharon & Frederick A. Klingenstein-Nathan G. Kase, MD Professor in the Departments of Pharmacological Sciences, Neuroscience, and Artificial Intelligence and Human Health, as well as the Dean of The Graduate School of Biomedical Sciences at the Icahn School of Medicine at Mount Sinai, in New York, USA. The overall goal of her research program is to obtain rigorous mechanistic insights into the structure, dynamics, and function of important classes of membrane proteins and prominent drug targets, including G protein-coupled receptors (GPCRs), transporters, channels, and 3 integrins. To this end, her lab uses several computational structural biology tools and rational drug design approaches, ranging from molecular modeling, bioinformatics, cheminformatics, molecular dynamics simulations, free-energy perturbations, machine learning, etc. A native of Italy, she received her Bachelor’s and Master’s degrees in Chemistry from the University Federico II in Naples. She pursued a Ph.D. in Computational Chemistry at the Second University of Naples and a postdoctorate in Computational Biophysics at the Molecular Research Institute in California, USA. Dr. Marta Filizola on the web Icahn School of Medicine at Mount Sinai Filizola Lab Wikipedia Twitter Linkedin ResearchGate Google Scholar Orcid PubMed Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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 >>

Join the scientific exchange in the room with the scientist, not watching from the audience. Access 200+ expert sessions at Dr. GPCR University. University / Live Masterclass Sessions In the room with the scientist, not watching from the audience. Live scientific exchanges with leading GPCR experts. Interactive, question-driven, frontier science. This isn't a lecture — it's a conversation with the people shaping GPCR discovery. Masterclass is included inDr. GPCR University Try it for 14 days Upcoming live sessions Your next Live Masterclass Session is waiting Each session focuses on a specific pharmacology or GPCR discovery topic, led by a recognized expert. Live Q&A means your questions get real answers. GPCR Desensitization in Health and Disease Dr. Adriano Marchese | Medical College of Wisconsin October 22, 2026 Receptor Signaling Details Introduction to GLP-1 pharmacology Dr. Marsha Pierce | Midewestern University October 29, 2026 Translational Pharmacology & Disease Models Details What makes this different? Not a lecture. Not a webinar. A scientific exchange. The Masterclass was created because the most valuable insights in GPCR science aren't captured in papers or conference talks. Scientist-to-scientist discussion Extended Q&A allows deeper exploration than typical presentations. You're engaging directly with the expert — not submitting a question to a moderator. Beyond conference time limits Topics are explored in greater depth than standard conference talks allow. Sessions focus on scientific reasoning, data interpretation, and real discovery problems. Focused audience of specialists Sessions bring together GPCR researchers, pharmacologists, and discovery scientists. The conversation stays at the right level because everyone in the room speaks the same scientific language. Every session recorded Can't make it live? Every Masterclass is recorded and available on demand in the library. Revisit the science anytime — over 200 sessions and growing. On-demand library 200+ expert sessions, available anytime Full recordings of every Masterclass session. Revisit the science at your pace — filter by category, level, or instructor. Explore all Recorded Masterclasses → The scientists Learn directly from world leaders in GPCR research Adriano Marchese Dmitry Veprintsev Matteo Pavan Terry Kenakin Andrew Tobin Jakob Höppner Samuel Hoare Yamina Berchiche Bryan Roth Kenneth Jacobson Sudarshan Rajagopal Davide Calebiro Marsha Pierce Terry Hébert What scientists say? From the people in the room I am a convert! I will keep Dr. GPCR and the offered resources in my work sphere Dr. Hoare is very experienced in the field. What came as a pleasant surprise was how didactical and well-thought-out his course was—highly recommended. The really unexpected was that the Q&A sessions reached the highest level—beyond excellent. GPCR researcher Thank you for bringing this course with Dr. Kenakin. I wish Dr. GPCR the best for the sake of promoting more educational opportunities that are sorely needed in the field GPCR researcher The content had enough depth to satisfy the hunger for theory while being full of practical knowledge GPCR researcher The best pharmacology teacher teaming up with the best GPCR community platform to help train and inspire the next generation of scientists. Also super-valuable for those of us learning how to teach pharmacology GPCR researcher Dr. Hoare's extensive and elaborative explanation of the topics at hand was excellent and very digestible. Thoroughly enjoyed learning from him GPCR researcher Dr. Kenakin is a leading expert in the field. Aside from his vast experience in drug development, not to mention his extensive publication record, Dr. Kenakin is a masterful teacher and communicator. GPCR researcher The course was very practical and easily translatable to experiments that we could do in our own labs. It was clear that Dr. Hoare is very in touch with the technical and human challenges we encounter in our work GPCR researcher About the GPCR Masterclass What is a GPCR Masterclass? The GPCR Masterclass is a live scientific discussion with a leading expert in GPCR pharmacology, receptor biology, or drug discovery. Sessions focus on research questions, experimental interpretation, and emerging challenges in GPCR science. Are the sessions live or recorded? Masterclass sessions are conducted live with an invited expert. After the event, recordings are added to the Masterclass course library, where Premium Members can access them on demand. Who should join? The Masterclass is designed for GPCR researchers, pharmacologists, and drug discovery scientists working in academia, biotech, and pharmaceutical research. Can I watch sessions later if I miss the live event? Yes. All sessions are recorded and available in the Masterclass course library for Premium Members. Can I watch sessions later if I miss the live event? Yes. All sessions are recorded and available in the Masterclass course library for Premium Members. How do I fit this in my schedule? You can attend the live discussion or watch the recording later. The Masterclass library allows members to revisit sessions at any time. What makes the Masterclass different from reading papers or textbooks? The Masterclass focuses on scientific interpretation and discussion. Experts explain how they think about pharmacological data, experimental design, and discovery challenges—insight that is rarely captured in publications. What happens during the live discussion? Each session begins with a focused presentation from the guest expert, followed by moderated discussion and questions from participants. The format allows deeper exploration of pharmacology concepts than typical conference presentations. Masterclass is included in Dr. GPCR University Live sessions, 200+ on-demand recordings, plus premium intelligence, jobs, events, and a community of GPCR scientists — all in one place. See what it feels like for 14 days. Try University for 14 days — $50 Your professional home in GPCR science. $499/year after trial.

<< Back to podcast list Strategic Partner(s) GPCR location matters with Dr. Gabriele Kockelkoren About Gabriele Kockelkoren I have a strong background in both physics and molecular biology and, accordingly, I strive in interdisciplinary environments. After completing a cum laude BSc. and MSc. in Nanobiology at the Technical University of Delft in The Netherlands, I pursued a PhD at the University of Copenhagen under the supervision of Prof. Dimitrios Stamou. In my PhD, I studied the nanoscale spatial organization of G protein-coupled receptors (GPCRs) at the plasma membrane of living cells. Importantly, my work revealed heterogeneous spatial patterns of receptor density and activation, that are modulated in a drug-dependent manner. These findings identify nanoscale GPCR spatial organization as an integral element of their activity and signaling. Currently, I am a Postdoctoral Fellow in the lab of Prof. Alice Ting developing programmable receptors for molecular sensing and controlling cellular behaviour. Gabriele Kockelkoren on the web Stanford University X LinkedIn Google Scholar ORCID ResearchGate Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Dr. Katarzyna Marcinkiewicz About Dr. Katarzyna Marcinkiewicz "Katarzyna is a Senior Editor at Nature Communications, which she joined in April 2020, following three years on the editorial teams of Nature Structural and Molecular Biology and Nature Biotechnology. She obtained her Ph.D. from Weill Cornell Graduate School of Medical Sciences in New York City, studying epigenetic changes in cancer. During her postdoctoral training at New York University School of Medicine, her research focused on cellular senescence. Katarzyna handles submissions in structural biology, biophysics and biochemistry, with a particular focus on membrane proteins and protein folding." Dr. Katarzyna Marcinkiewicz on the web LinkedIn Nature The Spectator Dr. GPCR Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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 Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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) Sri Kosuri About Dr. Sri Kosuri Sri is a biologist that has helped build technologies, labs, and companies in synthetic biology, functional genomics, and bioinformatics over the last 20 years. He is passionate about developing more rational ways to understand and engineer biology. Sri is a co-founder at Octant and an Associate Professor at UCLA in the Chemistry and Biochemistry Department. His lab has worked on building large-scale ways of empirically exploring questions in protein biochemistry, human genetic variation, gene regulation, chemical biology, synthetic biology, and functional genomics. Sri previously worked at the Wyss Institute and Harvard, where he built numerous technologies in gene synthesis, DNA information storage, gene editing, and large-scale multiplexed assays. He helped build Gen9, a gene synthesis company, as a member of the SAB and was the first employee of Joule Unlimited, an engineered algal biofuel company. He is a Searle Scholar (2015), NIH New Innovator (2014), and received his ScD in Biological Engineering at MIT and BS in Bioengineering at UC Berkeley. Sri is originally from New Jersey, Philadelphia, and Kansas and was born in North Carolina. He enjoys eating, getting outdoors, and traveling with his wife and two children. Dr. Sri Kosuri on the web Octant Kosuri Lab Twitter LinkedIn Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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 >>

Discover how Joseph Kim’s curiosity for science led him into GPCR research, drug discovery, and membrane protein biology—plus practical insights on building a scientific career. << Back to podcast list Strategic Partner(s) Anita Nivedha: Computational Dynamics of Ligand Bias in GPCR Signaling Scientific Abstract G protein–coupled receptors (GPCRs) transmit extracellular signals through conformational changes that propagate from ligand-binding sites to intracellular signaling partners. Understanding how ligand binding leads to specific signaling outcomes—particularly ligand bias toward G protein or β-arrestin pathways—remains a major challenge in GPCR pharmacology and drug discovery. In this conversation, Dr. Anita Nivedha discusses computational approaches to decoding signal propagation within GPCR structures. Using molecular dynamics simulations combined with network analysis of residue communication pathways, Dr. Nivedha describes how allosteric signaling within receptors can be quantified at atomic resolution. During her postdoctoral work, she developed a computational framework that maps communication pathways from ligand-binding pockets to intracellular effector interfaces, enabling prediction of ligand bias directly from structural simulations. The discussion explores how microscopic structural communication within receptors correlates with experimentally observed signaling outcomes, providing a bridge between structural biology and pharmacology. Dr. Nivedha also reflects on broader implications for receptor subtype selectivity, peptide receptor pharmacology, and the evolving role of computational pharmacology in modern drug discovery. Together, these perspectives illustrate how simulations can move beyond visualization to become quantitative tools for understanding receptor activation and guiding GPCR-targeted therapeutics. About the Guest Dr. Nivedha is a computational biologist specializing in molecular simulations and computational pharmacology. Her work focuses on understanding how ligand binding propagates structural signals through GPCRs using molecular dynamics simulations and network-based analysis of residue communication pathways. During her postdoctoral research, Dr. Nivedha developed computational approaches to quantify ligand bias by analyzing communication routes between extracellular ligand-binding sites and intracellular signaling interfaces. Her work has also explored receptor subtype selectivity and peptide-binding GPCRs, connecting structural dynamics to pharmacological outcomes relevant for drug discovery. Scientific Themes of the Conversation Allosteric communication networks within GPCR structures Computational quantification of ligand bias Molecular dynamics simulations of receptor activation Structural determinants of GPCR subtype selectivity Integrating computational pharmacology with experimental GPCR biology Translating structural dynamics into drug discovery insights Key Insights from the Conversation Computational Pathways Can Reveal Ligand Bias Dr. Nivedha describes how communication pathways inside GPCR structures can be mapped using molecular dynamics simulations. By counting signaling routes connecting ligand-binding sites to intracellular interfaces, simulations can reproduce experimentally measured ligand bias. Allosteric Communication Explains Signal Propagation Ligand binding does not directly trigger signaling. Instead, information travels through networks of interacting amino acids across the receptor structure, forming allosteric communication pathways that connect extracellular ligand binding to intracellular signaling outcomes. Simulations Provide Dynamic Views of Receptor Function Static structures capture only one moment in receptor activation. Molecular dynamics simulations allow researchers to observe proteins in motion and analyze conformational transitions that drive receptor signaling. Structural Communication Reveals Functional Residues Mapping communication networks identifies key residues involved in signal propagation. These residues may represent potential targets for allosteric modulators that reshape receptor signaling pathways. Computational Methods Complement Experimental Pharmacology Experimental assays measure pathway activation, but they do not directly reveal the structural mechanisms underlying signaling bias. Computational approaches provide a mechanistic bridge between receptor structure and pharmacological output. Subtype Selectivity Emerges from Subtle Structural Differences Even closely related receptor subtypes can display different ligand affinities. Structural simulations can reveal how binding pocket geometry and receptor dynamics contribute to subtype selectivity. Scientific Careers Often Evolve Unexpectedly Dr. Nivedha reflects on how her career in GPCR biology began unexpectedly during her postdoctoral work. What started as a general interest in protein dynamics evolved into a deep engagement with the GPCR field. Episode Timeline 00:00 — Introduction: From ligand binding to receptor signaling Overview of ligand bias and the challenge of tracing signal propagation within GPCR structures. 02:00 — Scientific background of Dr. Nivedha Bioinformatics training, computational chemistry, and early research in carbohydrate–protein interactions. 07:30 — First encounters with GPCR structural biology Transition from studying general protein dynamics to the complexities of GPCR signaling. 16:45 — Studying allosteric communication in GPCRs Introduction to computational tools for mapping communication pathways inside proteins. 18:30 — Quantifying ligand bias using molecular simulations Development of a computational framework linking communication pathways to signaling outcomes. 20:00 — Applications to subtype selectivity and receptor pharmacology Using structural communication analysis to explain differences in ligand affinity across receptor subtypes. 26:00 — Academic–industry collaborations in GPCR drug discovery Insights from collaborative research with pharmaceutical partners. 46:00 — Scientific turning points and career insights Key moments that shaped Dr. Nivedha’s research direction. 52:00 — Reflections on GPCR research and future directions Perspectives on the diversity and continuing importance of GPCR biology. Selected Quotes “Communication pathways connect the ligand-binding site to the intracellular signaling interface, and those pathways are made of residues along the way.” “By counting the number of communication pathways toward G proteins versus arrestins, we began to see correlations with experimental ligand bias.” “Molecular dynamics simulations allow us to simulate proteins in motion and understand the conformational changes that drive receptor activation.” “Simulations stopped being just visualizations—they became measurements that could inform predictions for drug discovery.” Full Transcript (Formatted for readability) Introduction Yamina Berchiche: Hello listeners, Yamina here. Welcome to the Dr. GPCR podcast. If you’ve ever wanted to measure ligand bias, you’ve probably looked at the activation of different signaling pathways. But how does the binding of a ligand at the extracellular pocket of a receptor redirect residues within the receptor to activate signaling? That remains difficult to trace today. My guest today is Dr. Anita Nivedha, a computational biologist studying allosteric communication in GPCRs. She uses molecular dynamics and network analysis to map signaling pathways through receptors. During her postdoctoral work on GPCR structure and function, one problem stood out: can simulations quantify ligand bias inside receptor structures? One evening running analyses alone in the lab, a pattern appeared. Communication routes toward G proteins differed from those toward arrestins. When she counted those pathways, the numbers tracked experimental bias. A computational framework for predicting ligand bias began to emerge. Those calculations linked microscopic communication within the receptor to macroscopic signaling outcomes. Suddenly, simulations were not just visualizations anymore—they were measurements. And measurement meant predictions for drug discovery. Before we dive into this episode, I invite you to check out the relevant links in the show notes. And now, let’s dive into this conversation with Dr. Nivedha. Guest Introduction Yamina Berchiche: Hello everyone, this is Yamina from Dr. GPCR. And I’m very excited today because this has been a long time in the works to have with me Dr. Anita Nivedha. Dr. Nivedha: Thank you so much for having me. I’m really excited for our conversation today. Yamina Berchiche: Let’s start at the beginning. Could you introduce yourself and tell our audience who you are and what you do? Dr. Nivedha: Absolutely. My name is Anita. I’m currently a senior scientist at a biotech in Toronto, Canada. Previously I worked at another company in Montreal offering computer-aided drug discovery services. Before that I was doing my postdoc in California in the lab of Dr. Nagarajan Vaidehi at City of Hope. That’s where I first got introduced to GPCRs. My PhD was in Georgia in the lab of Dr. Robert Woods, where I worked on carbohydrate ligands and docking scoring functions. My undergraduate degree was in bioinformatics in India, which is where my interest in computational approaches to biology started. Yamina Berchiche: Wonderful. And we did have Dr. Nagarajan on the podcast and I love chatting with her. She’s wonderful. Dr. Nivedha: Yeah, I actually listened to that podcast. I was very excited to see her on your podcast. Yamina Berchiche: She is wonderful. Thank you so much for that introduction. I have to ask—how did you get interested in science in general? Dr. Nivedha: Science was something I was interested in since middle school. I was always interested in biology, especially studying anatomy. At one point I was interested in becoming a medical doctor when I was younger. But as I grew up and learned more about biotechnology and the possibilities that existed, my interests diversified. Around high school I was introduced to programming. I started learning C and C++ programming and I really loved it. When it came time to choose my major for undergrad, I wanted something that combined both biology and computers. I didn’t even know such a field existed. But when I came across bioinformatics, I thought, “This is it.” It combined both things I liked. So my interest in science and computers kind of merged there, and that’s what I still do today. Women in Computational Science Yamina Berchiche: I love it. And I think other than you and Dr. Vaidehi, I don’t remember ever having female computational scientists on the podcast. And today is International Women’s Day, so we’re revealing when this podcast is being recorded. I was wondering if you could speak to your experience being a computational scientist. What’s the ratio of female versus male computational scientists in your experience? Dr. Nivedha: That’s a good question. When you mentioned that only a few female computational scientists have been on the podcast, I’m surprised—but also not surprised. During my PhD there was a better balance of men and women, although the lab was not purely computational. But since then, I’ve often been outnumbered. When I joined Dr. Vaidehi’s lab, I was the only woman apart from her initially. Later more women joined the group. But overall, I would say women are still underrepresented in computational fields. Discovering GPCRs Yamina Berchiche: You mentioned that you joined Dr. Vaidehi’s lab and that’s when you were first exposed to GPCRs. Do you remember the first time you looked at a GPCR on a computer? Was it just another protein target, or did you immediately feel it was something special? Dr. Nivedha: I’m trying to remember exactly when I first saw one. It was probably in VMD or another visualization tool we commonly use. At the time, I didn’t realize the full scope of GPCR biology. I didn’t yet appreciate how interesting and diverse they are, or how important they are as drug targets. Before that, my PhD focused on carbohydrate ligands interacting with proteins. So the proteins were more like partners for the glycans we studied. When I applied for postdocs, I was mostly interested in studying proteins in general—their structure, dynamics, and function. GPCRs were not specifically what I was looking for. But once I started working on them, I appreciated them more and more. Over time I realized how vast and exciting the field is. Postdoctoral Research Questions Yamina Berchiche: Let’s talk about your postdoc research. What were the main questions you were trying to answer? Dr. Nivedha: One of the main topics I worked on was allosteric communication in proteins. In GPCRs, a ligand binds at the extracellular side of the receptor. The result is activation of intracellular signaling partners like G proteins or β-arrestins. But how does the signal travel from the extracellular binding pocket to the intracellular interface? That transmission happens through communication pathways across the receptor structure. This is what we call allosteric communication. The lab had developed software to analyze these communication pathways. Using that framework, I worked on quantifying ligand bias computationally. We used molecular dynamics simulations and extracted communication pathways connecting the ligand binding site to intracellular interfaces. Then we compared pathways leading to G proteins versus β-arrestins. We applied this method to GPCR systems where experimental bias values were known. And interestingly, the computational results correlated with experimental measurements. That project became a collaboration with Boehringer Ingelheim and eventually led to a publication. Applications to Receptor Selectivity Dr. Nivedha: After that, I extended this work to study subtype selectivity. Some GPCR families contain closely related subtypes. Ligands may bind one subtype strongly but another weakly. Using communication pathway analysis and simulations, we explored how structural differences between receptor subtypes influence ligand affinity. I also worked on collaborative projects involving peptide-binding receptors, including angiotensin receptors. Industry Collaboration Yamina Berchiche: Your work involved collaboration with industry. What did you learn from that experience? Dr. Nivedha: It was actually my first interaction with industry researchers. Our collaborator at Boehringer Ingelheim was also a computational scientist with deep GPCR knowledge. That made the collaboration really productive. They provided suggestions that were directly relevant to our work. It was a great learning experience. It also showed me how important GPCR research is in pharmaceutical development. Seeing how computational methods could be applied to real drug discovery questions was very motivating. That experience influenced my later decision to pursue industry roles. Career Reflections and Scientific Turning Points Yamina Berchiche: I’d love to hear about some “aha moments” in your career. Dr. Nivedha: One moment happened very early when I chose bioinformatics as my undergraduate major. I remember standing in a hall reading a pamphlet describing the program. When I saw that bioinformatics combined biology and computing, I knew immediately that this was what I wanted to do. Another moment came during my postdoc while working on the ligand bias project. One Friday evening I was alone in the lab running analyses. I decided to compare the number of communication pathways leading to G protein versus arrestin interfaces. When I saw that those numbers tracked experimentally observed ligand bias, I realized we might have discovered something important. That moment led to the development of the computational method we later published. Favorite GPCRs Yamina Berchiche: Do you have a favorite GPCR? Dr. Nivedha: That’s a difficult question. I don’t think I have one favorite receptor. It often depends on what I’m studying at the time. For example, I became fascinated with adhesion GPCRs when I learned about them. I also find olfactory receptors fascinating because of how challenging they are to study. And now that I work with peptide drug modalities, I’m interested in peptide-binding GPCRs. So I keep discovering new receptors that do interesting things. That’s one of the reasons the GPCR field is so exciting. Closing Reflections Yamina Berchiche: Last question—the toughest one. What should we title this episode? Dr. Nivedha: Maybe something about how working on GPCRs was a happy accident in my career. I didn’t originally plan to work on them, but they ended up shaping my scientific path. Yamina Berchiche: I love that idea. Episode Outro Yamina Berchiche: Thank you to Dr. Nivedha for this fantastic conversation. This discussion explored computation as a tool to decode receptor signaling—from simulations to drug discovery. It reminds us that dynamics often hold the real mechanism. If you enjoyed this conversation, share it with a colleague. Subscribe to the Dr. GPCR podcast so you never miss a discussion. And remember: receptors don’t work alone—neither should you. Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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 >>

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 Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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 >>

Pfleger on NanoBRET live-cell assays, receptor complex pharmacology, and what it took to move GPCR biology from HEK cells to phase 2 clinical trials. << Back to podcast list Strategic Partner(s) Pfleger: NanoBRET, Receptor Complexes, and the Translation of GPCR Pharmacology GPCR pharmacology has long depended on recombinant systems in which receptors are expressed and studied as isolated proteins. But in living tissue, GPCRs do not operate alone - they form dynamic complexes with other receptors, scaffold proteins, and cytoskeletal components, and those interactions reshape conformation, ligand binding, and signaling output in ways that isolated assays cannot detect. Kevin Pfleger's research at the University of Western Australia sits at the intersection of assay technology, receptor pharmacology, and translational medicine. His group developed BRET and NanoBRET-based live-cell platforms that capture protein-protein interactions and signaling dynamics in real time, preserving the kinetic information that endpoint assays routinely discard. Those platforms have been applied across arrestin biology, receptor complex pharmacology, and the angiotensin and chemokine receptor systems, including CCR2. The conversation also covers what it means when cell biology reaches the clinic. Pfleger co-founded a biotech company that completed phase 2 clinical trials in focal segmental glomerulosclerosis and diabetic kidney disease - and watching protein levels fall in patients' urine is, for him, the reason most scientists enter medical research in the first place. About the Guest Kevin Pfleger is Professor, Director of Biomedical Innovation, and Head of Molecular Endocrinology and Pharmacology at the University of Western Australia and the Harry Perkins Institute of Medical Research. His research centers on GPCR functional interactions, with a focus on arrestin signaling, receptor complex pharmacology, and the angiotensin and chemokine receptor systems. He developed BRET and NanoBRET-based live-cell assay platforms now widely adopted across the GPCR field, and serves as Deputy Director of the Australian Research Council Centre for Personalised Therapeutics Technologies. Pfleger co-founded a publicly listed biotech company that has completed phase 2 clinical trials in focal segmental glomerulosclerosis and diabetic kidney disease, and holds leadership roles across Australian biomedical innovation and entrepreneurship. Scientific Themes of the Conversation Real-time vs. endpoint assays - why kinetics change the pharmacological picture GPCR receptor complexes and the limits of isolated receptor screens Bias signaling as a kinetic and time-dependent phenomenon NanoBRET and the evolution of live-cell assay design for GPCR biology Academic entrepreneurship and the path from bench to phase 2 clinical trials Funding diversification and the transferable skills embedded in PhD training Key Insights from the Conversation 1. Endpoint Assays Can Miss the Biology Entirely A single measurement at a fixed time point collapses all the kinetic information in a signaling event into one number. Pfleger describes profiles where the peak of a response occurs early and then subsides - and where an endpoint assay taken after that peak would return a flat or misleading result. The problem is not the assay format itself; it is the assumption that one time point is enough. 2. Bias Signaling Is a Kinetic Problem, Not Just a Pathway Problem Spider plots comparing signaling bias across multiple pathways are a standard output in GPCR pharmacology. Pfleger challenges a silent assumption embedded in most of them: that the time point chosen for each measurement is irrelevant. If bias has a kinetic component - and the evidence suggests it often does - then what gets called "biased" may be an artifact of when you looked, not what the receptor is actually doing. 3. Receptors in Complexes Behave Differently Than Receptors in Isolation Standard drug screens present a receptor as a discrete, isolated target. In the body, that receptor is complexing with other receptors, scaffold proteins, and cytoskeletal elements - and those interactions alter its conformation and drug-binding properties. Pfleger argues this is not a theoretical complication; it is a pharmacological reality that current screening approaches largely bypass. Understanding receptor complexes is where the next layer of selectivity and specificity in drug discovery lives. 4. BRET Went From a Handful of Labs to the Go-To Platform When Pfleger began working with bioluminescence resonance energy transfer in GPCR research, it was a niche technology used by a small number of groups worldwide. That has changed. The development of NanoBRET - including live-cell ligand binding assays built on CRISPR-expressed receptors - contributed to an adoption curve that now spans most GPCR pharmacology labs. For Pfleger, the reach of the technology is not a source of pride as much as a signal that the field recognized what real-time, live-cell measurement offers that nothing else does. 5. The Long Road From HEK Cells to a Patient's Urine Pfleger describes a particular moment from the phase 2 clinical trial his spin-out company ran in kidney disease: seeing urinary protein levels fall in patients on the compound. He had spent years characterizing arrestin interactions with angiotensin and CCR2 receptors in cell-based systems, working through the logic of functional selectivity in disease-relevant pathways. That cell biology eventually became a clinical hypothesis, then a compound, then a trial result. What made it humbling, he notes, were the calls from patients' families asking to get into the trial. 6. The PhD Trains You for Far More Than the Bench The skills built during doctoral training - managing time, coordinating teams, working within resource constraints, communicating under uncertainty - map directly onto the skills required in industry, entrepreneurship, and scientific leadership. Pfleger made this case from personal experience: spending years pitching to rooms of executives taught him that the win-win logic he needed there was not foreign to scientific collaboration. It was the same logic, applied to different stakeholders. The analytical discipline of the PhD, he argues, is not a niche credential. It is a transferable toolkit most PhD students do not realize they have built. Episode Timeline Timestamps are AI-generated from the transcript and may require minor adjustment after final audio editing. 00:00 Introduction 01:36 Pfleger's philosophy: science as a team sport 03:54 From Cambridge to Edinburgh - an accidental PhD and the origin of a career 06:10 Working on biosignaling before the field had a name for it 09:12 Postdoc pivot: from GnRH receptors to arrestin interactions in Australia 12:47 The spin-out - how a discovery became a phase 2 clinical trial in kidney disease 16:56 Why grant-only funding is becoming unsustainable and what to do instead 22:21 What a PhD actually trains you for 25:42 NanoBRET, live-cell assay design, and the CRISPR ligand binding platform 27:54 Why endpoint assays miss the peak - the case for real-time kinetics 29:44 Bias signaling as a time-dependent measurement 32:26 Screening receptors in complexes, not in isolation 40:03 When cell biology reached the patient Selected Quotes "The number of times we see very interesting profiles and if you were to do an endpoint assay, you would completely miss the point because you've missed the peak. A lot of the time you get a signature, and you can compare those signatures and see a lot of nuance." "Traditionally screening has happened with receptors in isolation, but in reality, in the body, these receptors are complexing. They're interacting with the cytoskeleton, with other proteins, with other receptors, and that will change their conformation. That will change their ability to bind." "We were actually seeing the protein levels in the urine going down in the patients. That is really why I think most people get into medical research. It's very humbling." "A PhD is not just a training in working at a bench and writing a thesis. It's so many other things - whether it's about time management, people management, managing a budget. These are all business skills. And these are all skills that can be transferred." About this episode Dr. Pfleger trained as a pharmacologist and obtained his Ph.D. at the University of Edinburgh. I sat down with Kevin to chat about GPCRs, pharmacology, and his contributions to the field in both the academic and biotech worlds. Professor Pfleger has developed extensive expertise in profiling receptor binding and function at the molecular and cellular levels over the last 20 years, particularly involving GPCRs. He also has globally-recognized expertise in bioluminescence resonance energy transfer (BRET) technology, including his patented Receptor-Heteromer Investigation Technology (Receptor-HIT) for studying heteromers. Kevin is also Director, Biomedical Innovation at The University of Western Australia (UWA) and the MTPConnect Western Australian Life Sciences Innovation Hub. He is Head of Molecular Endocrinology and Pharmacology at the UWA Centre for Medical Research and Harry Perkins Institute of Medical Research, Deputy Director of the Australian Research Council Centre for Personalised Therapeutics Technologies, Chief Scientific Advisor to Dimerix, and co-founder of RAGE Biotech . He currently serves on the Board of the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists and is a member of the British Pharmacological Society International Advisory Group. Join me and learn more about Kevin’s work and how he manages all his responsibilities. Dr. Kevin Pfleger on the web LinkedIn ResearchGate Pubmed Google Scholar University of Western Australia Harry Perkins Institute of Medical Research Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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. Kaavya Krishna Kumar About Dr. Kaavya Krishna Kumar "I am a postdoc in Prof. Brian Kobilka's lab at Stanford University, USA. I work on understanding the activation mechanism of different Families of GPCRs." Dr. Kaavya Krishna Kumar on the web Journal of Biology Chemistry Stanford University Google Scholar LinkedIn Dr. GPCR Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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. Khaled Abdelrahman About Dr. Khaled Abdelrahman Dr. Khaled Abdelrahman graduated in 2006 with a BSc in Pharmaceutical Sciences from Alexandria University (Egypt) followed by MSc in Pharmacology in the same university that was conferred in 2009. He joined the laboratory of Dr. William Cole at the University of Calgary in 2010 for his Ph.D. where he studied the molecular basis underlying altered cerebrovascular function and blood flow in type 2 diabetes. In 2015, He joined Dr. Stephen Ferguson’s laboratory in the Departments of Cellular & Molecular Medicine and Neuroscience at the University of Ottawa as a Postdoctoral Fellow to explore novel G protein-coupled receptor (GPCR) candidates that can be targeted pharmacologically to slow neurodegeneration. He has been also studying what aspects of GPCR signaling are regulated in a sex-selective manner and how this can influence drug discovery in the area of neurodegenerative diseases. He is also a Registered Pharmacist in Canada and held two of the most prestigious Clinician Postdoctoral Fellowships offered by Alberta Innovates and Canadian Institutes of Health Research. He received the Canadian Society of Pharmacology and Therapeutics Postdoctoral and Publication awards along with many Young Scientist Awards from the American Society for Pharmacology and Experimental Therapeutics. Dr. Khaled Abdelrahman on the web Twitter PubMed Google Scholar Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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. Prasenjit Saha About Dr. Prasenjit Saha I conducted my doctoral research at the Indian Institute of Science, Bangalore, India, to investigate the mechanisms behind rare mitochondrial diseases, which can lead to heart failure, muscle fatigue, and neurodegenerative disorders. I am now working at the Cleveland Clinic in Ohio, USA, studying the gut microbiome and its impact on cardiovascular disease (CVD). Specifically, I am interested in understanding dysregulated G-protein coupled receptor (GPCR) signaling linked to atherosclerosis and diabetes. My research goal is to identify novel cellular target receptors of human gut microbe-derived metabolites that are pathologically linked to CVD. Discovering these receptors would be a significant breakthrough in cardiovascular biology as they could be targeted for therapeutic purposes. During my post-doctoral research, I was part of a study that identified the receptors of a novel human gut microbe-derived metabolite called phenylacetylglutamine (PAG), which is linked to cardiovascular disease. This study demonstrated that PAG is a potential diagnostic marker for CVD as it causes serious fatal conditions such as thrombus formation, which can block blood vessels. In this study, I discovered adrenergic receptors (α2A, α2B, and β2-adrenergic receptors) that serve as the gut microbial metabolite (PAG) receptor and characterized the receptor-metabolite interaction. More recently, I have shifted my focus to identifying allosteric modulators of host G-protein-coupled receptors (GPCRs) that contribute to cardio-metabolic disorders. Traditional drug discovery efforts have focused on agonists and antagonists that bind to the orthosteric site of the receptor. However, the pursuit of allosteric modulators has gained attention as they have the potential to fine-tune cellular responses with greater selectivity among the subtypes of GPCRs. My long-term plan is to conduct research in the field of receptor biology, with a focus on GPCRs. They are the largest, most versatile, and most ubiquitous class of plasma membrane receptors and serve as targets for more than one-third of all prescribed drugs currently used in the treatment of human diseases all over the world. Dr. Prasenjit Saha on the web Google Scholar Pubmed LinkedIn Dr. GPCR Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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) Nicole Perry-Hauser About Nicole (Nicki) Perry-Hauser I am a postdoctoral research fellow endeavoring to build a productive, independent scientific research career in adhesion G protein-coupled receptor (aGPCR) biology. My long-term research interests involve resolving signaling pathways downstream of aGPCRs and establishing how/if these receptors’ adhesive properties influence signaling events, and in turn, whether signaling impacts synapse formation and neuronal wiring. Mutations in aGPCRs have been linked to various neuropsychiatric phenotypes, and my work will provide a basis for understanding aGPCR biology in the nervous system. Nicole (Nicki) Perry-Hauser on the web LinkedIn Research Gate Pubmed Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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) Dylan Eiger About Dylan Eiger Dylan Eiger is currently an MD/Ph.D. student at Duke University School of Medicine. He received his B.S. in Chemistry from Duke University in 2016 where he worked in the lab of Dr. Stephen Craig and studied polymer chemistry and material science. He is currently finishing his Ph.D. in the lab of Dr. Sudarshan Rajagopal, a former postdoctoral fellow of Dr. Robert J. Lefkowitz . Dylan's graduate research focuses on the mechanisms underlying biased signaling at GPCRs, specifically, the role of differential receptor phosphorylation (phosphorylation barcodes) and subcellular GPCR signaling in directing functionally selective responses. He primarily studies the chemokine receptor CXCR3 as it has three naturally occurring ligands and thus serves as an endogenous example of biased agonism. After finishing his MD/Ph.D., Dylan plans to complete his residency training in Internal Medicine and subsequently pursue fellowship training in Cardiology. He hopes to continue his research on biased agonism at GPCRs with a particular focus on the treatment of cardiovascular disease. Dylan Eiger on the web LinkedIn Twitter PubMed Website Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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 >>

A conversation with Dr. Tore Bengtsson on β₂-adrenergic receptor signaling, muscle metabolism, and how GPCR pharmacology can lead to new therapies for metabolic disease. << Back to podcast list Strategic Partner(s) Tore Bengtsson: Rethinking β₂-Adrenergic Signaling in Metabolic Disease Scientific Abstract This conversation with Dr. Tore Bengtsson , professor of physiology at Stockholm University, explores how β-adrenergic receptor signaling can be reimagined to address metabolic disease, muscle physiology, and energy balance. Dr. Bengtsson’s research spans sympathetic nervous system signaling, brown adipose tissue biology, and skeletal muscle metabolism—fields deeply connected to obesity, type 2 diabetes, and metabolic health. A central theme of the discussion is the pharmacology of the β₂-adrenergic receptor , a GPCR traditionally associated with bronchodilation but increasingly recognized for its broader physiological roles. Dr. Bengtsson describes how classical β₂ agonists stimulate muscle growth and metabolic changes but are limited by receptor desensitization. His work focuses on developing novel β₂-adrenergic ligands that selectively engage signaling pathways without triggering rapid desensitization, enabling sustained metabolic effects. The conversation also examines how GPCR signaling is far more complex than a single downstream pathway. Instead, receptors integrate multiple signaling outputs, temporal dynamics, and interactions with other pathways to shape physiological outcomes. Dr. Bengtsson discusses how understanding this signaling complexity opens opportunities to design drugs that promote beneficial metabolic responses such as muscle growth and increased energy expenditure. Listeners gain insight into how basic GPCR pharmacology can translate into therapeutic strategies targeting metabolism, aging, and metabolic disease. About the Guest Dr. Tore Bengtsson is a professor of physiology at Stockholm University whose research focuses on sympathetic nervous system signaling, metabolic regulation, and skeletal muscle physiology. His work investigates how β-adrenergic receptors regulate energy metabolism, muscle growth, and glucose homeostasis. Dr. Bengtsson began his research career studying brown adipose tissue under the mentorship of Dr. Barbara Cannon and Dr. Jan Nedergaard, pioneers in thermogenesis research. His laboratory now explores how β₂-adrenergic receptor signaling can be manipulated to influence metabolism and muscle physiology. He is also an entrepreneur and founder of biotechnology companies translating GPCR pharmacology into therapeutic development. Scientific Themes of the Conversation β-adrenergic receptor pharmacology and signaling bias Sympathetic nervous system control of metabolism Brown adipose tissue and thermogenesis Skeletal muscle metabolism and glucose homeostasis GPCR signaling complexity and pathway selectivity Translating receptor pharmacology into metabolic therapeutics Key Insights from the Conversation A Childhood Physiological Experiment Sparked a Scientific Career Dr. Bengtsson recounts a formative experience when his father pushed him into icy water as a child to demonstrate survival in cold conditions. The intense physiological response—an adrenaline surge and rapid adaptation to cold—sparked his lifelong fascination with sympathetic nervous system signaling and stress physiology. Stress Is Not Always Negative A recurring theme in the discussion is that physiological stress is often misunderstood. Short bursts of stress—whether exercise, cold exposure, or sympathetic activation—can trigger adaptive responses that improve metabolic function and resilience. Muscle Is Central to Metabolic Health While brown fat has received considerable attention, Dr. Bengtsson emphasizes the dominant role of skeletal muscle in metabolic regulation. Approximately 75% of glucose disposal occurs in muscle, making muscle physiology central to metabolic diseases such as type 2 diabetes. Classical β₂ Agonists Have a Fundamental Limitation Traditional β₂-adrenergic agonists can stimulate muscle growth and fat loss but lose effectiveness over time due to receptor desensitization. This pharmacological limitation prevents their long-term use for metabolic therapies. GPCRs Do Not Produce a Single Signal Dr. Bengtsson highlights that GPCR signaling is inherently multidimensional. Activation of a receptor can generate multiple signaling pathways, and different ligands can bias signaling toward specific outcomes. Understanding this complexity is essential for modern drug discovery. Absence of a Signal Can Be a Discovery One of Dr. Bengtsson’s key scientific breakthroughs came from an unexpected experimental result: glucose uptake without detectable cAMP signaling. Rather than dismissing the result as an error, this observation led to the realization that β₂ signaling could be separated into distinct pathways. Scientific Discovery Requires Intellectual Independence Dr. Bengtsson advises young scientists to shift from passively following instructions to actively questioning experiments and interpretations. True scientific thinking begins when researchers take intellectual ownership of the questions they pursue. Episode Timeline 00:00 Introduction and research focus of Dr. Bengtsson 03:00 A childhood experiment that sparked interest in physiology 07:00 Cold exposure, sympathetic signaling, and brown fat research 10:00 β₂-adrenergic receptors and muscle physiology 15:00 Exercise, metabolism, and pharmacological modulation of muscle growth 17:30 Early research on brown adipose tissue and thermogenesis 22:30 Translating academic discoveries into biotech companies 25:00 GPCR signaling complexity and biased signaling 36:00 A key experimental observation leading to a new drug concept 38:30 Advice for young scientists and intellectual independence Selected Quotes “You will not know what happens before you do the experiment.” “People think a receptor produces one signal. In reality, a receptor produces many signals.” “Sometimes the most important discovery is when a signal is missing.” “You have to move from being told what to do to thinking for yourself.” Full Transcript (Formatted for readability — full transcript preserved) Yamina Berchiche: Hello, everyone. This is Yamina from Dr. GPCR. And today I'm very excited to have with me Dr. Tore Bengtsson. Dr. Bengtsson: Tore Bengtsson. And you got it right. Yamina Berchiche: I'm happy to have you on. For those who don't know, we've been chasing each other and postponing this conversation several times. I'm very excited that we're finally able to do it today. Dr. Bengtsson: Thank you. I'm very happy to be here. Yamina Berchiche: Let's start at the beginning. Could you introduce yourself and tell us about your research? Dr. Bengtsson: I'm a professor in physiology at Stockholm University. I've been working with pre-diabetes, type 2 diabetes, obesity, and the mechanisms behind these diseases for about 25 years. I'm especially interested in β-adrenergic receptors because I believe they regulate far more physiological processes than people typically assume. I'm also an entrepreneur. I've started several companies. One is Sigrid Therapeutics, which focuses on digestion and metabolic regulation. Another company, Atrogi, is based on our research on β₂-adrenergic receptors and the development of new drugs. We’ve already completed Phase I clinical trials and are preparing for Phase II. Yamina Berchiche: If you were not a scientist, what would you be doing? Dr. Bengtsson: I think I might have been a historian or a writer. I like storytelling. I'm very interested in Viking runes and ancient rune stones in Scandinavia. I can actually read runic inscriptions, and I find it fascinating to interpret what these stones tell us about history. Yamina Berchiche: How did you become a scientist? Dr. Bengtsson: I'll tell you a story I don't share very often. When I was about ten years old, I lived on an island in the Stockholm archipelago. My father and I went ice skating frequently during the winter. One summer he asked me: “What happens if you fall through the ice?” I said I didn't know. He replied: “We should test it.” Months later, during winter, he cut a hole in the ice. I asked what he was doing. He said he was catching a big fish. Suddenly he pushed me into the icy water. I went under, looked up at the hole in the ice, and quickly swam out. I remember the intense adrenaline surge. My body reacted instantly. I wasn't even cold at first. Walking home later I started to freeze, but in that moment I experienced a powerful physiological response. That event sparked my lifelong fascination with sympathetic nervous system activation. Yamina Berchiche: So your father pushed you into science quite literally. Dr. Bengtsson: Yes — and into physiology. Yamina Berchiche: And that connects directly to your later work on brown fat and sympathetic signaling. Dr. Bengtsson: Exactly. I've spent many years studying brown adipose tissue and how sympathetic activation stimulates thermogenesis. Later I became increasingly interested in skeletal muscle metabolism and how β₂-adrenergic signaling affects muscle growth and glucose metabolism. Yamina Berchiche: Could you talk about how β₂-adrenergic signaling relates to muscle growth? Dr. Bengtsson: For many years it's been known that β₂ agonists can stimulate muscle growth and reduce fat. This has been observed in athletes and even in livestock production. But traditional β₂ agonists lose effectiveness over time because the receptor becomes desensitized. The body adapts, requiring higher doses. That makes them unsuitable as long-term therapeutic drugs. So about 15–20 years ago I began working on the idea that we need a new type of β₂ agonist—one that activates the receptor differently and avoids desensitization. That’s what we’ve now achieved with new compounds that stimulate the receptor in a novel way. Yamina Berchiche: You mentioned something very important earlier: GPCRs don’t produce a single signal. Dr. Bengtsson: Yes. Traditionally people thought receptor activation leads to one downstream pathway. But GPCRs activate multiple signaling pathways simultaneously. Different ligands can bias signaling toward different pathways. That means we can design compounds that favor beneficial physiological responses while avoiding unwanted effects. That is exactly what makes GPCR pharmacology so fascinating and powerful. Yamina Berchiche: You mentioned an important experimental moment that led to your drug concept. Dr. Bengtsson: Yes. A doctoral student ran an experiment measuring glucose uptake. The compound produced strong glucose uptake but almost no cAMP signaling. She thought the experiment had failed. But I realized this might be something important: glucose uptake without cAMP. And that turned out to be correct. That observation opened the door to separating signaling pathways and designing new β₂ ligands. Yamina Berchiche: What advice would you give to young scientists? Dr. Bengtsson: Young scientists often follow instructions without asking why. Real science begins when you take control of the question. You must move from being told what to do to thinking independently. You have to be in the driver's seat of your own thinking. Yamina Berchiche: That’s a powerful message. Dr. Bengtsson: And another lesson I learned from my wife: success often depends not just on knowledge but on understanding how other people think. Science is not just experiments. It's communication, persuasion, and collaboration. Yamina Berchiche: Dr. Bengtsson, thank you very much for the conversation. Dr. Bengtsson: Thank you. This was great. Yamina Berchiche: Bye. Dr. Bengtsson: Bye-bye. Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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 >>

Discover how GPR65 reshapes our understanding of GPCR signaling and its role in cancer, with Dr. Ian Chronis on the Dr. GPCR podcast. << Back to podcast list Strategic Partner(s) Signals, pH, and Discovery : Cracking GPCR Mysteries with Dr. Ian Chronis In this episode, we welcome Dr. Ian Chronis, a recent Ph.D. graduate preparing to begin his postdoctoral work at the University of Michigan. Host Yamina Berchiche sets a welcoming tone as they dive into Ian’s unique academic journey—from early interests in medicine to his pivot toward pharmacology and GPCR research. His story offers valuable insights for anyone navigating the path from student to scientist. Ian discusses how his experiences at the University of Chicago and the University of Michigan shaped his scientific curiosity, particularly around G protein-coupled receptors (GPCRs) . His research centers on the beta-2 adrenergic receptor and GPR65 , a proton-sensing receptor with promising implications in cancer biology. He shares fascinating findings from his work on GPR65 , highlighting its unusual constitutive internalization and its ability to signal from acidic endosomes. This dual functionality—environmental sensing and compartment-specific signaling—offers a new layer of complexity in GPCR behavior. Yamina underscores the therapeutic potential of GPR65, especially in the context of cancer immunotherapy, and how understanding receptor activity in acidic micro environments could unlock new therapeutic strategies. Throughout the episode, Ian reflects on the value of a supportive lab culture , the need for better experimental tools in GPCR signaling , and the importance of engaging with the broader GPCR research community to drive innovation. The conversation wraps with a playful exchange about possible podcast titles, with Yamina suggesting "Ancient Greek Chemistry and GPCRs"—a nod to Ian’s heritage and the wide-ranging themes covered. This episode is both educational and inspiring, offering a behind-the-scenes look at a rising scientist’s journey in the ever-evolving world of GPCR research. About Ian Chronis I recently finished my PhD in the lab of Dr. Manoj Puthenveedu at the University of Michigan, where I am now working as a postdoc. My research has looked at the trafficking and signaling of adrenergic and proton-sensing receptors, with specific focus on identifying novel regulatory proteins governing their function. Ian Chronis on the web LinkedIn Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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 >>