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<< Back to podcast list Dr. GPCR Podcast Strategic Partners Dr. Daniel Wacker About Dr. Daniel Wacker I obtained my B.Sc. degree from the University of Munich performing work in the lab of Dr. Roland Beckmann with a brief stay at Cambridge University, UK, working in the lab of the late Dr. Kiyoshi Nagai . I then obtained an M.Sc. at the University in Munich working e.g. in the lab of Patrick Cramer . I next moved to Rockefeller University in NYC to work in the lab of the late Dr. Guenter Blobel , before starting my Ph.D. in 2009 at The Scripps Research Institute in La Jolla. There I obtained my Ph.D. in the lab of Dr. Ray Stevens in 2013 solving several GPCR crystal structures, including that of the first serotonin receptor. I then moved to UNC at Chapel Hill to do postdoctoral work in the lab of Dr. Bryan Roth where I established GPCR structural biology and learned the ins and outs of molecular pharmacology and in vitro drug discovery. In 2018 I started my own lab at the Icahn School of Medicine at Mount Sinai in NYC, where I have been working on structure-function and drug discovery of GPCRs and transporters. Dr. Daniel Wacker on the web Website LinkedIn Twitter PubMed Dr. GPCR Ecosystem 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 Recent Podcast Articles How GPCR Collaboration Built an Innovation Engine From Pipettes to Platforms: The Evolution of GPCR Research How GPCR Spatial Signaling Sparked a Scientific Journey Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Dr. GPCR Podcast Strategic Partners Re-cap of Endocrine Metabolic GPCR 2024 with the Organizers About Dr. Aylin Hanyaloglu Dr. Aylin Hanyaloglu has been a Principal Investigator at Imperial College London since 2007. She received her BSc in Human Biology from King’s College London in 1997, and while her Ph.D. commenced at the MRC Human Reproductive Sciences Centre, Edinburgh, a move to Perth, Australia resulted in her Ph.D. in Molecular Endocrinology being awarded in 2002 with Distinction from the University of Western Australia. Dr. Hanyaloglu undertook her postdoctoral training at the University of California, San Francisco with Professor Mark von Zastrow where she identified novel core cellular machinery critical for G protein-coupled receptor trafficking and signaling. Her research focuses on understanding the fundamental cell biological mechanisms regulating GPCR activity, including spatial control of GPCR signaling and receptor crosstalk, and applying these mechanisms for distinct GPCRs in diverse physiological and pathophysiological systems, with particular focus on women's health, pregnancy, and nutrient sensing in the gut. Her work is currently funded by Biotechnology and Biological Sciences Research Council (BBSRC), Diabetes UK, Wellcome Trust, and the Medical Research Council. Dr. Aylin Hanyaloglu on the web LinkedIn Endocrine Metabolic GPCRs Researchgate Twitter Imperial College London Elsevier Loop Dr. GPCR About Dr. Caroline Gorvin "Dr. Caroline Gorvin is a Wellcome Trust & Royal Society Sir Henry Dale Fellow at the Institute of Metabolism and Systems Research, University of Birmingham. She obtained her PhD in 2012 from the University of Oxford, where her research focused on the cellular mechanisms by which mutations in a chloride-proton antiporter cause the renal disorder Dent’s disease. Caroline continued to undertake postdoctoral research in Oxford, investigating the signalling and trafficking of the G protein-coupled receptor (GPCR), calcium-sensing receptor, and its role in calcium homeostasis. Caroline moved to the University of Birmingham in 2018 to establish her research group investigating metabolic GPCRs. Her current research focuses on how metabolic GPCRs cross-talk and interact to regulate appetite and bone metabolism." Dr. Caroline Gorvin on the web University of Birmingham Endocrine Metabolic GPCRs Society of Endocrinology Google Scholar ResearchGate Loop Twitter Dr. GPCR About Dr. Alejandra Tomas "Dr. Alejandra Tomas is a molecular cell biologist and Senior Lecturer at the Department of Metabolism, Digestion and Reproduction, Imperial College London. She obtained a PhD in Biochemistry from University College London and spent several years in Switzerland working on the study of membrane trafficking processes in pancreatic beta cells before returning to the UK, first to her Department at UCL and then to lead a laboratory at Imperial following the receipt of an MRC New Investigator Award in 2015." Dr. Alejandra Tomas on the web Imperial College London Endocrine Metabolic GPCRs ResearchGate Google Scholar LinkedIn Twitter Dr. GPCR 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 Recent Podcast Articles How GPCR Collaboration Built an Innovation Engine From Pipettes to Platforms: The Evolution of GPCR Research How GPCR Spatial Signaling Sparked a Scientific Journey Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

Discover how Dr. Tom Sakmar and Dr. Ilana Kotliar built a multiplexed platform to map GPCR-RAMP interactions and uncover autoantibody-driven GPCR signaling in disease. << Back to podcast list Dr. GPCR Podcast Strategic Partners Hacking GPCRs: Tools, Tech & Drug Discovery with Tom Sakmar & Ilana Kotliar In this episode, host Dr. Yamina Berchiche reconnects with Dr. Tom Sakmar , Professor at Rockefeller University, and Dr. Ilana Kotliar , his former graduate student, to explore the development of powerful multiplex tools designed to map GPCR-RAMP interactions across the receptor superfamily. What began as a focused exploration into Family B GPCRs evolved into a comprehensive resource for the GPCR research community — bridging wet-lab experimentation, open-access tools, and computational biology. 1. A Long-Term Vision Realized “We've done this work for the past 30 years.” – Tom Sakmar Dr. Sakmar recounts how a fateful phone call from Bruce Merrifield decades ago inspired his lifelong focus on Family B GPCRs. That curiosity laid the foundation for a broader investigation into receptor activity-modifying proteins (RAMPs) . The lab’s early partnership with students like Emily Lorenzen catalyzed a transition from single-receptor studies to multiplexed approaches , opening doors to high-throughput interaction mapping. 2. From Curiosity to Collaboration “We decided to evaluate the multiplexing methods... and found this Luminex assay.” – Tom Sakmar After exploring several screening techniques, the lab adopted the Luminex bead-based assay , which allowed simultaneous detection of multiple GPCR-RAMP interactions. This methodology was enhanced through collaboration with Jochen Schwenk’s lab at SciLifeLab in Karolinska. The result: a scalable platform to analyze hundreds of interactions with minimal sample usage. 3. A Rotation That Changed Everything “I really love this project. I want to take it forward.” – Ilana Kotliar Dr. Kotliar joined the Sakmar lab as a rotation student and immediately saw the project’s potential. She expanded the original Family B focus to encompass the entire GPCR superfamily , building a digital and physical toolkit to systematically investigate GPCR-RAMP biology. Her goal was ambitious: map the complete interactome and validate findings in both overexpression and native contexts. 4. Tools for the Community “We have a library on Addgene... dual-epitope tagged GPCRs.” – Ilana Kotliar The team developed two main assets: A web interface to visualize antibody validations and GPCR-RAMP interactions. A DUET-tagged GPCR library (220 constructs) available through Addgene , enabling labs to explore interactions with ease. These tools are fully open to academic researchers , with wide applicability beyond just RAMPs — including scaffold proteins, disease markers, and heterodimerization partners. 5. Driving Impact through Open Science “500+ requests have come in for these clones.” – Tom Sakmar Dr. Sakmar highlights the vital role of Addgene in distributing the DUET library. The logistical lift was considerable — involving extensive 96-well plate work and documentation — but the team prioritized accessibility over proprietary restrictions. Their ethos: empower fellow scientists, not profit from them. 6. Beyond GPCR-RAMP: New Avenues “What if your favorite scaffold protein interacts with GPCRs?” – Tom Sakmar The constructs aren’t limited to RAMP interaction studies. They can be used to probe GPCR associations with any protein , from cytoskeletal scaffolds like 14-3-3 and P11 to disease-linked interactors . The system is modular and adaptable, opening doors for systems biology and context-specific interaction mapping . 7. A Diagnostic Future “Autoantibodies targeting GPCRs might drive disease.” – Tom Sakmar One especially exciting avenue is autoimmune and infectious diseases . The team envisions using these tools to detect GPCR autoantibodies , which are implicated in conditions like long COVID and Graves’ disease . Unlike blocking antibodies, some autoantibodies activate GPCRs , potentially driving pathophysiology — a paradigm-shifting concept in GPCR immunology. 8. From Many to One: De-Orphanization and Precision Focus “You can use this system to de-orphanize receptors.” – Ilana Kotliar While the toolkit enables broad interactome analysis , it’s also valuable for narrowing in on orphan GPCRs — receptors with unknown ligands or function. This could accelerate discovery of therapeutic targets by combining multiplex data with focused downstream assays. In Ilana’s words, it’s a powerful way to “go from many back to one.” 9. The Shift Toward Technology-Driven Biology “Today’s students want to multiplex, miniaturize, and engineer tools.” – Tom Sakmar Dr. Sakmar reflects on the generational shift in research culture. Instead of focusing on a single receptor, students now gravitate toward platforms , biosensors , and data-rich assays . The multiplex strategy aligns perfectly with this evolution, providing scalable approaches to biological discovery. 10. Global Collaboration and Computational Frontiers “There is no science that ends at a national border.” – Tom Sakmar The success of this project hinged on international collaboration and a multidisciplinary mindset . As the field advances, the computational layer — including AlphaFold and structural prediction tools — will play an increasingly pivotal role. This synergy of wet-lab, in silico, and community-driven resources promises a new era for GPCR systems biology . Summary made with AI ________ Key Takeaway This episode is more than a conversation — it’s a masterclass in tool-driven discovery , community science, and the future of GPCR interaction mapping . If you’re working on GPCRs, this is your call to leverage these tools , ask new questions, and help unlock previously hidden layers of receptor biology . Keyword Cloud GPCR-RAMP interactions , multiplex assays , GPCR research community , Dr. GPCR ecosystem , GPCR data platform , GPCR autoantibodies , Addgene GPCR library , GPCR training program , GPCR drug discovery , GPCR online course Summary created by AI ________ About Tom Sakmar Tom Sakmar is a physician-scientist and Rockefeller University professor dedicated to drug discovery and chemical biology research, mainly involving GPCRs. He and his artist/designer wife, Karina Åberg, have three teenage children. Tom Sakmar on the web LinkedIn ResearchGate Pubmed ORCID Google Scholar Rockefeller University Wikipedia About Ilana Kotliar Ilana Kotliar is a 5th year graduate student in the lab of Dr. Thomas Sakmar at The Rockefeller University and just recently defended her PhD thesis. Ilana uses chemical biology-based methods to study the regulation and protein-protein interactions of GPCRs. Ilana’s research is multi-disciplinary and involves a close collaboration with the lab of proteomics expert Dr. Jochen Schwenk, located 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. Ilana Kotliar on the web Google Scholar LinkedIn Twitter 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 Recent Podcast Articles How GPCR Collaboration Built an Innovation Engine From Pipettes to Platforms: The Evolution of GPCR Research How GPCR Spatial Signaling Sparked a Scientific Journey Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Dr. GPCR Podcast Strategic Partners Dr. Alexander S. Hauser About Dr. Alexander S. Hauser Alexander is currently a postdoc as a member of the personalized medicine cluster in Copenhagen and at the Institute of Biological Psychiatry in Roskilde working with the UK Biobank and other large-scale population cohorts. Alexander has a big interest in the integration of large biomedical data in genomics, structural biology, pharmacology, and pharmacoepidemiology with innovative computational methods to gain novel insights into receptor biology. During his Ph.D. with David Gloriam at the Department of Drug Design and Pharmacology in Copenhagen, he worked on novel analytical methods to identify human signaling systems and thereby discovered endogenous peptides activating several orphan receptors. Alexander had a research sabbatical with Madan Babu at the MRC Laboratory of Molecular Biology in Cambridge, UK, where he was working on the impact of genetic variations on drug response. He received the “HC Ørsted Research talent prize” and “Bayer Pharmaceuticals Ph.D. Award” for his work on GPCRs. Dr. Alexander S. Hauser on the web Twitter ResearchGate University of Copenhagen LinkedIn Google Scholar Dr. GPCR Ecosystem 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 Recent Podcast Articles How GPCR Collaboration Built an Innovation Engine From Pipettes to Platforms: The Evolution of GPCR Research How GPCR Spatial Signaling Sparked a Scientific Journey Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Dr. GPCR Podcast Strategic Partners Dr. Bruno Giros About Dr. Bruno Giros Dr. Giros' lab investigates how molecular changes at the nerve synapse might impact integrated behavior and what we might learn from these mechanisms to cure mental illness. After doctoral training at the Pierre and Marie Curie University in Paris and a short internship at Genentech Inc. in South San Francisco, he joined the CNRS as a Research Fellow in 1987 in the INSERM Laboratory directed by Jean-Charles Schwartz in Paris, where he cloned and characterized dopamine D2 and D3 receptor subtypes. From 91 to 94, he was an assistant professor at Duke University in North Carolina, working with Marc Caron and Robert Lefkowitz (2012 Nobel Prize in Chemistry) to characterize several neurotransmitter transporters and kinases and establish the first knock-out for these genes. In 1999, in France, Dr. Giros created the INSERM/CNRS laboratory on the "Neurobiology of Psychiatric Disorders," first in Créteil with Marion Leboyer, then at the University of Paris-Sorbonne with Hervé Chneiweiss. Since 2008, he has arrived at McGill University as a Canada Research Chair. At McGill, his laboratory has two main axes of research: 1) Studying interindividual vulnerability to chronic stress and depression and; 2) Understanding the role of phenotypically defined subpopulations of striatal neurons in motor and cognitive functions. Bruno Giros has trained 59 master's, doctoral and postdoc students, most of his trainees obtain positions in the academic or private sectors or are currently pursuing postdoctoral research training or have entered medical studies. Dr. Giros has published more than 200 publications with an H factor of 79 and 32,000 citations (Google Scholar) and has received several distinctions, including the CNRS silver medal, the FRM "Young Researcher" prize, the ISI “Highly Cited” and F-1000 in Pharmacology, and recently received the Heinz Lehmann Award from the Canadian College of NeuroPsychopharmacology and the distinguished James B. McGill Professor Award. Dr. Bruno Giros on the web Dougles Research Center LinkedIn Google Scholar Researchgate Dr. GPCR 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 Recent Podcast Articles How GPCR Collaboration Built an Innovation Engine From Pipettes to Platforms: The Evolution of GPCR Research How GPCR Spatial Signaling Sparked a Scientific Journey Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Dr. GPCR Podcast Strategic Partners 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 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 Recent Podcast Articles How GPCR Collaboration Built an Innovation Engine From Pipettes to Platforms: The Evolution of GPCR Research How GPCR Spatial Signaling Sparked a Scientific Journey Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Dr. GPCR Podcast Strategic Partners Inês Pinheiro, Monserrat Avila Zozaya & Yamina Berchiche About Inês Pinheiro PharmD by training and Ph.D. candidate in Hartley's lab at the University of Geneva. As a young researcher fascinated by chemokine receptors, molecular pharmacology, drug discovery, and immuno-oncology. Inês Pinheiro on the web LinkedIn University of Geneva Twitter Dr. GPCR Ecosystem About Monserrat Avila Zozaya I am a cell biologist interested in studying GPCRs, especially adhesion GPCRs. Motivated by my scientific passion, I recently started a postdoctoral fellowship to study the role of GPCRs in the mechanisms of pain and its comorbidities. Monserrat Avila Zozaya on the web Antony Boucard Lab Dr. GPCR Ecosystem About Yamina Berchiche Dr. Yamina A. Berchiche is the founder of Dr. GPCR, an ecosystem designed to bring together stakeholders interested in using G-Protein Coupled Receptors (GPCRs), that control virtually everything in the body, as drug targets. The mission of Dr. GPCR is to accelerate GPCR drug discovery by sharing the latest research and technology advances in the field and providing exposure to scientists through the Dr. GPCR podcast. Dr. Berchiche obtained her Master’s and Ph.D. in Biochemistry at the University of Montreal in Canada before training at The Rockefeller University in New York and the National Institutes of Health in Bethesda, Maryland. She developed expertise over the past two decades studying structure/function relationships of GPCRs using live-cell bioluminescence resonance energy transfer (BRET). Her work focused on chemokine receptors, members of the GPCR family that control cell movement in the body. Yamina Berchiche on the web Website LinkedIn Facebook Twitter ResearchGate PubMed Google Scholar Dr. GPCR Ecosystem 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 Recent Podcast Articles How GPCR Collaboration Built an Innovation Engine From Pipettes to Platforms: The Evolution of GPCR Research How GPCR Spatial Signaling Sparked a Scientific Journey Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Dr. GPCR Podcast Strategic Partners Dr. Sai Prasad Pydi About Dr. Sai Prasad Pydi Dr. Sai Prasad Pydi obtained his Ph.D. from the University of Manitoba – Canada, where he was introduced to G protein-coupled receptors (GPCRs) by Prof. Prashen Chelikani . His doctoral research focused on the structural and functional characterization of bitter taste receptors (T2Rs). In 2014, Dr. Pydi joined Dr. Jurgen Wess’s lab at the National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK) - NIH, USA as a postdoctoral fellow and trained on understanding the physiological role of GPCR signaling and beta-arrestins in diabetes and obesity. In February 2021, Dr. Pydi joined BSBE department at IIT-Kanpur. The main target of Dr. Pydi's laboratory is to develop GPCR-based drugs for the treatment of obesity and Type 2 Diabetes (T2D) by exploring metabolically important signaling pathways in immune cells and insulin-sensitive tissues (liver, pancreas, skeletal muscle, adipose tissue, and brain). His laboratory uses knock-out and transgenic mouse models, along with different cell culture systems, to understand the role of immune cell GPCRs and their cross-talk with other insulin-sensitive tissues regulating glucose and lipid metabolism. Dr. Sai Prasad Pydi on the web Molecular Metabolism & Cell Signaling Laboratory Website Twitter.com Research Gate PubMed Google Scholar Dr. GPCR Ecosystem 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 Recent Podcast Articles How GPCR Collaboration Built an Innovation Engine From Pipettes to Platforms: The Evolution of GPCR Research How GPCR Spatial Signaling Sparked a Scientific Journey Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

Home → Flash News → terrys corner model drug response Published on July 10, 2025 Category Terry's Corner What if a single experimental snapshot could predict an entire in vivo drug profile in a range of organs? In Terry’s Corner latest lesson, discover how pharmacologic models do just that. From historical linkage theory to dynamic probability models, the comparison of data to theory will be discussed. 🟢 Read the full breakdown: ✳️ https://www.ecosystem.drgpcr.com/post/what-if-you-could-predict-drug-behavior-with-just-a-snapshot #GPCR #DrGPCR #pharmacology #DrugDiscovery #TerryKenakin #FoundationalScience Previous Next Recent Articles

Full Agenda Adhesion GPCR workshop 2024 CINVESTAV, Mexico City, Mexico October 23-25 Download PDF Program HERE < Back to Full Agenda Complimentary Reception dinner MENU Four Mushroom Soup Tomato, Panela Cheese, and Spinach tower with Oregano Vinaigrette Cane Sugar and Arbol Chile Lacquered Duck Monte Cristo Chocolate Cake Coffee or Tea Vegetarian option* -Mushroom-stuffed chiles on refried bean sauce- instead of the duck < Previous Session Next Session >

Full Agenda Adhesion GPCR workshop 2024 CINVESTAV, Mexico City, Mexico October 23-25 Download PDF Program HERE < Back to Full Agenda Session V Structural mechanisms of AGPCR signaling and function Structural Determinants Of GAIN Domain Autoproteolysis And Cleavage Resistance Of Adhesion G Protein-Coupled Receptors Fabian Pohl Structural studies of the CELSR1 extracellular region reveal a compact multidomain module of fourteen domains which regulates signaling Sumit Bandekar Unveiling the GPS Cleavage Mechanism in ADGRL1 with QM/MM Florian Seufert Structural Determinants Of GAIN Domain Autoproteolysis And Cleavage Resistance Of Adhesion G Protein-Coupled Receptors Fabian Pohl Abstract "The GPCR autoproteolysis-inducing (GAIN) domain is a hallmark feature of adhe-sion G-protein coupled receptors (ADGRs), as this extracellular domain contains an integral agonistic sequence (Stachel) for activation via binding to the 7-transmembrane (7TM) helical domain of the receptor. Many ADGRs are autoproteo-lytically cleaved at the GPCR proteolysis site (GPS), an HXS/T motif within the GAIN domain. However, several ADGRs can be activated without GPS cleavage. We de-termined the crystal structure of the human ADGRB2/BAI2 hormone receptor (HormR) and GAIN domains and found that this ADGR is resistant to autoproteolysis despite the presence of a canonical HLS sequence at the GPS. By structural com-parison and with the help of molecular dynamics (MD) simulations we identified several unique structural features that are important for autoproteolytic cleavage, beyond the canonical HXS/T motif. Disruption of these features reduced autoproteo-lytic activity in ADGRL1/LPHN1 and restored cleavage competence of AD-GRB3/BAI3. Furthermore, conservation analysis indicates that wild type ADGRB2 and ADGRB3 are GPS cleavage-incompetent receptors." Authors & Affiliations "Fabian Pohl1, Florian Seufert2, Yin Kwan Chung3, Daniela Volke1, Ralf Hoffmann1, Torsten Schöneberg4, Tobias Langenhan3, Peter W. Hildebrand2, Norbert Sträter1 1 Institute of Bioanalytical Chemistry, Leipzig University, Deutscher Platz 5, 04103 Leipzig, Germany 2 Institute of Medical Physics and Biophysics, Leipzig University, Härtelstr. 16-18, D-04107 Leipzig 3 Rudolf-Schönheimer-Institute of Biochemistry, Division of General Biochemistry, Leipzig University, Johannisallee 30, D-04103 Leipzig 4 Rudolf-Schönheimer-Institute of Biochemistry, Division of Molecular Biochemis-try, Leipzig University, Johannisallee 30, D-04103 Leipzig" About Fabian Pohl "Mar 2023 – Today Postdoc, University Leipzig, Group of Prof. Langenhan Apr 2016 – Nov 2022 PhD candidate, University Leipzig, Group of Prof. Sträter Oct 2011 – Mar 2016 Master of Science in chemistry, University Leipzig Oct 2008 – Sep 2011 Bachelor of Science in chemistry, University Leipzig" Fabian Pohl on the web Langenhan Lab Structural studies of the CELSR1 extracellular region reveal a compact multidomain module of fourteen domains which regulates signaling Sumit Bandekar Abstract "Cadherin EGF Laminin G seven-pass G-type receptors (CELSRs) are conserved adhesion G protein-coupled receptors; they are essential for embryogenesis and neural development. CELSRs have large and enigmatic extracellular regions (ECRs) with nine cadherin repeats and a variety of adhesion domains which couple cell adhesion to signaling. CELSRs regulate planar cell polarity, including the closure of the neural tube. Despite numerous cell and animal studies, molecular details on CELSR proteins are sparsely available, precluding an integrative understanding of CELSR biology. Here, we report the 3.8 Å cryo-EM reconstruction of the CELSR1 ECR which enables unambiguous assignment of the 14 domains within the structure. These domains form a compact module mediated by robust and evolutionarily conserved interdomain interactions. This compact module provides a plethora of potential ligand binding sites for the various adhesion domains within the structure and hints at a model where the compact module could be pulled apart by robust mechanical force. We present biophysical evidence that the CELSR1 ECR forms an extended dimer in the presence of Ca2+, which we propose represents the cadherin repeats dimerizing in a configuration similar to protocadherins. We employ cellular assays with full-length CELSR1 and truncation constructs to assess the adhesive and signaling functions of this protein. We assign the N-terminal CADH1-8 module as necessary for cell adhesion and we show the C-terminal CAHD9-GAIN module regulates signaling. Our work provides molecular context to the literature on CELSR function and lays the groundwork for further elucidation of structure/function relationships." Authors & Affiliations "Garbett, Krassimira, Kordon, Szymon P., Shearer, Tanner, Sando, Richard C.*, and Araç, Demet* Department of Biochemistry and Molecular Biology, The University of Chicago Neuroscience Institute, Institute for Biophysical Dynamics, and the Center for Mechanical Excitability, The University of Chicago, Chicago, IL, 60637, USA. Department of Pharmacology, Vanderbilt Brain Institute, Vanderbilt University, Nashville, TN 37240, USA." About Sumit Bandekar "I am an NIH F32 postdoctoral fellow in the Araç Laboratory at the University of Chicago. I study adhesion GPCRs using structural biology perspective and I am interested in how the large multidomain extracellular region regulates receptor function. In my free time, I enjoy biking around Chicago and trying new breweries and restaurants." Sumit Bandekar on the web Araç Laboratory at UChicago X (Twitter) LinkedIn Unveiling the GPS Cleavage Mechanism in ADGRL1 with QM/MM Florian Seufert Abstract "Adhesion G-protein coupled receptors (aGPCR) are a family of 32 mammalian proteins with a defining conserved GPCR autoproteolysis inducing (GAIN) domain that catalyzes receptor self-cleavage at a GPCR proteolysis site (GPS). The autoproteolytic mechanism has been previously proposed, but remains to be validated.⁠ A previous computational study has uncovered variable flexible protein regions, whose dynamics mediate solvent-accessibility of the catalytically active GPS triad HL|S/T, however classical molecular dynamics approaches fall short of explaining the chemical reaction.⁠ Using a multiscale QM/MM approach - combining computational quantum mechanics with classical molecular dynamics - to study the GAIN domain cleavage mechanism of ADGRL1 reveals the sequence of events at the electronic level, suggesting relative energies for the individual states during the reaction, and provides insight into the structural determinants for a successful GPS cleavage exceeding the catalytically active GPS triad. By directly scanning and comparing energetic sequences of reaction steps, the most likely pathway and the individual contribution of surrounding protein residues can be elucidated. A stable π-edge contact with a conserved phenylalanine and a protonated glutamate side-chain catalyze the reactant conformation. MD simulations with the parameterized ester intermediate reveal a protonation-dependent dynamic desolvation of the GPS for subsequent ester hydrolysis by restricting water conformations. Mutational experiments on residues of interest showed that restoring the Phe-His interaction in the uncleaving ADGRB3 GAIN domain partially re-instates cleavage, while its deletion reduces cleavage in the ADGRL1 GAIN domain.⁠ We present a two-step GPS cleavage model and respective determinants of the reaction." Authors & Affiliations "Chung, Yin Kwan2, Pohl, Fabian2, Batebi, Hossein1 Sträter, Norbert3 , Langenhan, Tobias2 & Hildebrand, Peter Werner1 1 Institute of Medical Physics and Biophysics, Medical Faculty, Leipzig University, Germany 2 Rudolf Schönheimer Institute of Biochemistry, Division of General Biochemistry, Medical Faculty, Leipzig University, Germany 3 Institute of Bioanalytical Chemistry, Leipzig University, Germany" About Florian Seufert "Florian Seufert has studied Biochemistry in Leipzig, before joining the Hildebrand Lab in Leipzig for his PhD." Florian Seufert on the web LinkedIn ResearchGate < Previous Session Next Session >

Home → Flash News → A new study from the Hudson Lab at the University of Glasgow shows that the FFA receptor antagonist AH7614 is actually an inverse agonist - suppressing fat cell formation, boosting lipolysis and reducing glucose uptake. Explore how targeting FFA4 could help fight metabolic disorders. Catch up with the latest research conducted in the Hudson lab in Ep. 161 of the Dr. GPCR Podcast. Subscribe to the Dr. GPCR Newsletter 📰 and get the latest GPCR News delivered to your inbox ➡️https://www.ecosystem.drgpcr.com/gpcrs-in-cardiology-endocrinology-and-taste/inverse-agonism-of-the-ffa4-free-fatty-acid-receptor-controls-both-adipogenesis-and-mature-adipocyte-function #GPCR #drGPCR #FFA4 #metabolism #adipocytes” Published on April 7, 2025 Category GPCR Weekly News A new study from the Hudson Lab at the University of Glasgow shows that the FFA receptor antagonist AH7614 is actually an inverse agonist - suppressing fat cell formation, boosting lipolysis and reducing glucose uptake. Explore how targeting FFA4 could help fight metabolic disorders. Catch up with the latest research conducted in the Hudson lab in Ep. 161 of the Dr. GPCR Podcast. Subscribe to the Dr. GPCR Newsletter 📰 and get the latest GPCR News delivered to your inbox ➡️ https:// www.ecosystem.drgpcr.com/gpcrs-in-cardiology-endocrinology-and-taste/inverse-agonism-of-the-ffa4-free-fatty-acid-receptor-controls-both-adipogenesis-and-mature-adipocyte-function #GPCR #drGPCR #FFA4 #metabolism #adipocytes Previous Next Recent Articles

Home → Flash News → Unlock the full potential of the Dr. GPCR platform by updating your profile 🧬 Find like-minded scientists, and colleagues who work on the same topic as you 🙌 ✳️Go to https://www.ecosystem.drgpcr.com/account/my-account and update your profile #gpcr #drgpcr Published on January 22, 2025 Category Dr. GPCR Profiles Unlock the full potential of the Dr. GPCR platform by updating your profile 🧬 Find like-minded scientists, and colleagues who work on the same topic as you 🙌 ✳️Go to https://www.ecosystem.drgpcr.com/account/my-account and update your profile #gpcr #drgpcr Previous Next Recent Articles

<< Back to podcast list Dr. GPCR Podcast Strategic Partners Scott Struthers R. Scott Struthers, Ph.D., is our co-founder and has served as our President and Chief Executive Officer since December 2008. Prior to Crinetics, he was senior director and head of endocrinology and metabolism at Neurocrine Biosciences, Inc., from 1998 to 2008. At Neurocrine, he initiated and led the effort to discover and develop orally active, nonpeptide GnRH antagonists, including elagolix. Prior to Neurocrine, from 1995 to 1998, he co-founded ScienceMedia Inc. to develop eLearning solutions for the life sciences and higher education markets. Between 1992 to 1995 he led contract research efforts at Biosym Technologies to develop and apply computational tools for drug discovery. In 2021, Dr. Struthers co-founded and serves as board chair at Radionetics Oncology, a pharmaceutical company focused on the discovery and development of novel radiotherapeutics for oncology indications. In addition, he is a member of the board of directors of the San Diego Entrepreneurs Exchange, a nonprofit organization that provides resources for early-stage start-ups, which he co-founded in [2009.] R. Scott Struthers on the web LinkedIn Google Scholar Crinetics Radionetics Dr. GPCR Ecosystem 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 Recent Podcast Articles How GPCR Collaboration Built an Innovation Engine From Pipettes to Platforms: The Evolution of GPCR Research How GPCR Spatial Signaling Sparked a Scientific Journey Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Dr. GPCR Podcast Strategic Partners Brendan Wilkins About Brendan Wilkins "Brendan completed his undergraduate training at the University of New South Wales (UNSW) Sydney, Australia in 2016 with first class Honours in Pharmacology. In his Honours year, Brendan explored small molecule allosteric modulators of the β2-adrenoceptor under the tutelage of Dr Angela Finch. Since then, Brendan worked as a research assistant at the Victor Chang Cardiac Research Institute where he investigated the orphan G protein-coupled receptor (GPCR), GPR37L1. Brendan is now a final year PhD candidate in the Orphan Receptor Laboratory headed by Associate Professor Nicola J Smith at UNSW Sydney, Australia. Brendan’s PhD project focuses on the orphan GPCR GPR146. This project aims to characterise the molecular pharmacology of GPR146 and to validate the proposed ligands of GPR146 in line with IUPHAR-NC guidelines on deorphanisation of orphan GPCRs. Brendan is currently looking for post-doctoral positions to begin in mid-2024" Brendan Wilkins on the web UNSW Sydney Google Scholar ResearchGate LinkedIn Twitter Dr. GPCR 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 Recent Podcast Articles How GPCR Collaboration Built an Innovation Engine From Pipettes to Platforms: The Evolution of GPCR Research How GPCR Spatial Signaling Sparked a Scientific Journey Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Dr. GPCR Podcast Strategic Partners Dr. Debbie Hay About this episode Dr. Debbie Hay is presently a professor at the Department of Pharmacology and Toxicology at the University of Otago after spending 18 years at the University of Auckland. Her work is primarily focused on class B GPCRs and their interactions with RAMPs. Debbie obtained a Ph.D. in Molecular Pharmacology from Imperial College London in the UK. She has gained experience from working in academia and at GSK as an industrial trainee. Join me and learn more about Debbie’s career and what she learned through her experiences as a scientist. Dr. Debbie Hay on the web LinkedIn Wikipedia University of Otago University of Auckland Google Scholar Pubmed Research Gate Twitter Dr. GPCR Ecosystem 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 Recent Podcast Articles How GPCR Collaboration Built an Innovation Engine From Pipettes to Platforms: The Evolution of GPCR Research How GPCR Spatial Signaling Sparked a Scientific Journey Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Dr. GPCR Podcast Strategic Partners Dr. Terry Hébert About this episode Dr. Terry Hébert is a Professor within the Department of Pharmacology & Therapeutics at McGill University. Much of his work is based on GPCR signaling in the context to cardiovascular diseases. In this special episode of the Dr.GPCR podcast , we re-connected with Dr. Terry Hebert to chat about how he and his team has been adapting to the new reality of working remotely. Terry tells us about the importance of adapting, communicating, and being mindful of those around us. Dr. Terry Hébert on the web Terry Hébert | Institute of Health Sciences Education Hébert Lab LinkedIn Hébert Lab The GPCR Consortium PubMed Dr. GPCR Ecosystem 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 Recent Podcast Articles How GPCR Collaboration Built an Innovation Engine From Pipettes to Platforms: The Evolution of GPCR Research How GPCR Spatial Signaling Sparked a Scientific Journey Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Dr. GPCR Podcast Strategic Partners 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 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 Recent Podcast Articles How GPCR Collaboration Built an Innovation Engine From Pipettes to Platforms: The Evolution of GPCR Research How GPCR Spatial Signaling Sparked a Scientific Journey Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

Full Agenda Adhesion GPCR workshop 2024 CINVESTAV, Mexico City, Mexico October 23-25 Download PDF Program HERE < Back to Full Agenda Plenary Lecture Identification and Functional Characterization of Adhesion GPCRs As Steroid Hormone Receptors and Hearing and Balance Receptors Abstract Only Available for AGPCR24 Attendees About Jin-Peng Sun "Since starting my laboratory in 2011, I has focused on G protein coupled receptors, in particular, the ligand identification, physiological functions and molecular mechanism of biased signaling of GPCRs. Our first main research aspect is the identification of endogenous ligand of GPCRs. We have identified the receptor subfamily to sense the steroid hormones. For instance, membrane receptor GPR97 is able to sense glucocorticoid to mediate its rapid actions, the progesterone and 17-hydroxyprogesterone membrane receptor are GPR126. We also identified DHEA, DHEAS and DOC are endogenous ligands of GPR64 etc (Nature, 2021a, Nat Chem Biol 2022, PNAS 2022b). Our second main research aspect is dissecting the molecular mechanism underlying sensation of force, ordor, itch and taste by GPCRs. We have elucidated the mechanism of receptors' perception of itch, olfactory and force (Nature 2021b, 2022a, 2022b, 2023a, 2024). Our third main research aspect is working mechanism of GPCR. For arrestin mediated biased signaling, we have proposed the “flute model” and “poly proline region docking theory” etc. to explain the arrestin mediated GPCR functions (Nature communications, 2015, 2021, 2022; PNAS 2021, Molecular Pharmacology, 2017; Recommended by Faculty 1000, Nature Chemical Biology 2018). We identified that arrestin can mediated AT1R/TRPC3 or M3R/TRPC3 coupling by forming a complex of AT1R/β-arrestin-1/PLCγ/TRPC3 or M3R//β-arrestin-1/TRPC3 (Nature communications, 2017, Nature communications, 2018). We also identified that orphan receptor GPR64 forms complex with β-arrestin-1 and CFTR at apical membrane of efferent ductulus to regulate the salt/water metabolism (eLife 2018, Faculty 1000 recommendation). Our fourth main research aspect is ligand coding mechanisms and structural aided drug discovery of GPCR. We have decoded the mechanisms underlying recognition of fish oil (unsaturated fatty acids) and other lipids by GPCRs (Science 2023, Science Advance 2021, PNAS 2023, Nature Metabolism 2023), recognition of amine containing hormones by GPCRs (Cell 2021, 2023, Nature 2023b), bile acids or its derivatives by GPCRs (Nature 2020)." Jin-Peng Sun on the web Google Scholar LinkedIn < Previous Session Next Session >

Full Agenda Adhesion GPCR workshop 2024 CINVESTAV, Mexico City, Mexico October 23-25 Download PDF Program HERE < Back to Full Agenda Session I Tethered agonist - dependent/independent activation mechanism in AGPCRs Signaling Properties of ADGRL3 Signe Mathiasen An ECR-Mediated and TA-independent Mechanism of aGPCR Activation: Direct Communication of Extracellular Region with Transmembrane Domain in a Holo-Adhesion GPCR Demet Araç Heterogeneity of Tethered Agonist Signaling in Adhesion G Protein-Coupled Receptors Andrew Dates Discriminating between the extracellular scaffolding and G protein signaling roles of GPR56/ADGRG1 via the characterization of a non-cleavable point mutant knock-in mouse, H381S Frank Kwarcinski Tethered Peptide Activation Mechanism of Adhesion GPCRs Peng Xiao Signaling Properties of ADGRL3 Signe Mathiasen Abstract Only available for AGPCR 24 Workshop Attendees Authors & Affiliations "Rosell, Júlia (1) Holmkvist, Jesper L. (1) Arastoo, Mohammad Reza (1) Vejre, Phillip C. (1) Regmi, Rajesh (1) Perry-Hauser, Nicole A. (2) Bendix, Poul Martin (3) Javitch, Jonathan A. (2) Mathiasen, Signe (1) 1. Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. 2. Departments of Psychiatry and Molecular Pharmacology and Therapeutics, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, USA; Division of Molecular Therapeutics, New York State Psychiatric Institute, New York, New York, USA 3. Niels Bohr Institute, Faculty of Natural Sciences, University of Copenhagen, Copenhagen, Denmark" About Signe Mathiasen "2022-present Assistant Professor (Tenure Track) and Group Leader Department of Biomedical Sciences, University of Copenhagen. 2020 – 2022: Assistant Professor Department of Biomedical Sciences, University of Copenhagen. 2014-2021: Postdoc / Assistant Professor Department of Psychiatry, Columbia University, New York, USA. New York State Psychiatric Institute, Research Foundation for Mental Hygiene, New York, USA. Postdoc Supervisor Professor Jonathan Javitch 2013: PhD in Nanoscience/Biophysics. Department of Chemistry, University of Copenhagen, Copenhagen Denmark. PhD Supervisor Professor Dimitrios Stamou." Signe Mathiasen on the web University of Copenhagen Mathiasen Group An ECR-Mediated and TA-independent Mechanism of aGPCR Activation: Direct Communication of Extracellular Region with Transmembrane Domain in a Holo-Adhesion GPCR Demet Araç Abstract "According to the Tethered Agonist (TA)-mediated model of aGPCR activation, the ECR acts as a protective cap for the TA peptide to hide it within the GAIN domain. However, several recent observations suggest that other mechanisms of aGPCR activation are possible. For example, some aGPCRs do not undergo autoproteolysis, which is required for TA release. Even the aGPCRs that are cleaved do not always require cleavage for mediating some aspects of wild type functions. It has been suggested that the TA can regulate receptor signaling without coming out of the GAIN domain or by being partially exposed, however the recent TA-bound 7TM structures of multiple aGPCRs showed that the critical phenylalanine residue and other important TA residues have to reach deep into the 7TM orthosteric pocket for receptor activation, suggesting that non-release or partial release of the TA is unlikely to activate the receptor. In this talk, I summarize accumulating data from our lab and the aGPCR field that suggests an additional model in which the conformation of the Extracellular Region (ECR) has a direct role in modulating the 7TM signaling, independently of TA-mediated activation. Our results provide evidence for the ECR-mediated activation of aGPCR as a complementary mechanism for the TA-mediated activation of aGPCRs. Many biological forces are smaller than 200 pN, the force that is needed to separate the TA from the GAIN domain. To sense these smaller forces, and to regulate aGPCR function on and off, a mechanism that does not depend on ECR dissociation and TA exposure might be at work. At low force or no force conditions, aGPCR may be reversibly regulated by binding and dissociation of a ligand to the ECR without ECR shedding and TA exposure. In this ECR-mediated mechanism of activation, the ECR-7TM communication is altered by transient interactions between ECR and 7TM. The TA peptide remains at its original position and is not involved in signaling. Because the TA-mediated mechanism is a “one and done” mechanism that is irreversible and prevents the receptor from going back to its inactive resting state, the ECR-mediated mechanism may operate in situations where a reversible regulation is needed. The ECR-mediated mechanism may also enable responding to compressing forces on the receptor, that directly “push” on the protein. In cases where a large “pulling” force is executed on the ECR, the ECR may be removed from the 7TM releasing the tethered agonist and activating the aGPCR irreversibly but acutely. ECR-mediated mechanism opens new possibilities for drugging aGPCRs. Future work that dissects different activation mechanisms of aGPCRs in different physiological contexts will shed light on this fascinating family of receptors. " Authors & Affiliations "Kordon Szymon P.1, 2, Cechova Kristina3, Bandekar Sumit J.1, 2, Ethan Dintzner1, 2, Leon Katherine1, 2, Dutka Przemysław1, Siffer Gracie3, Kossiakoff Anthony A.1, Sando Richard 4, Vafabakhsh Reza3, Araç Demet1, 2 1. Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago; 2. Neuroscience Institute, Institute for Biophysical Dynamics, and Center for Mechanical Excitability, The University of Chicago, 3. Department of Molecular Biosciences, Northwestern University; 4. Vanderbilt University" About Demet Araç "Demet was an undergraduate at Bilkent University in Turkey, where she majored in Molecular Biology and Genetics. She moved to the University of Texas Southwestern Medical Center at Dallas in 2000 to work with Dr. Jose Rizo-Rey as a graduate student to elucidate the mechanisms of neurotransmitter release. After finishing her graduate training, she joined Dr. Axel Brunger’s lab at Stanford University to study the structure and function of cell-adhesion proteins at the synapse. In 2013, Demet began her independent research career at the University of Chicago within the Department of Biochemistry and Molecular Biology." Demet Araç on the web Araç Laboratory at UChicago X (Twitter) Heterogeneity of Tethered Agonist Signaling in Adhesion G Protein-Coupled Receptors Andrew Dates Abstract Only available for AGPCR 24 Workshop Attendees Authors & Affiliations "Daniel T.D. Jones (Harvard Medical School); Jeffrey S. Smith (Harvard Medical School, Brigham and Women's Hospital); Meredith A. Skiba (Harvard Medical School); Maria F. Rich (University of Cincinnati School of Medicine); Maggie M. Burruss (Harvard Medical School); Andrew Kruse (Harvard Medical School); Stephen C. Blacklow (Harvard Medical School)" About Andrew Dates "Drew Dates received his B.S. in Biological Chemistry from Carnegie Mellon University in 2018. As an undergraduate, he studied opioid receptor trafficking and G protein conformational dynamics in the laboratories of Manojkumar Puthenveedu and Roger Sunahara, respectively. As part of his doctoral work in the Blacklow laboratory at Harvard Medical School, Drew studied structure-function relationships in the Adhesion Family of GPCRs." Andrew Dates on the web Harvard Medical School Discriminating between the extracellular scaffolding and G protein signaling roles of GPR56/ADGRG1 via the characterization of a non-cleavable point mutant knock-in mouse, H381S Frank Kwarcinski Abstract Only available for AGPCR 24 Workshop Attendees Authors & Affiliations ""Tyler F. Bernadyn, Mariane Nascimento, Xinyi Lu, Pauline L. Pan, Michael Holinstat and Gregory G. Tall Department of Pharmacology, University of Michigan "" About Frank Kwarcinski "I am research faculty within the department of Pharmacology at the University of Michigan. I work under the supervision of Dr. Gregory Tall and our research primarily focuses on the structural and biochemical characterization of adhesion GPCRs (AGPCR) for mechanism of action and pathogenesis studies. We utilize several genetically modified mouse models to investigate requirements for receptor activator and continuously work to identify novel chemical modulators of AGPCRs through assay development and high-throughput screening efforts. I have previous work experience at two separate contract research organizations centered on assay development, and I am formally trained as a chemical biologist." Frank Kwarcinski on the web LinkedIn Tethered Peptide Activation Mechanism of Adhesion GPCRs Peng Xiao Abstract Only available for AGPCR 24 Workshop Attendees About Peng Xiao "I joined Prof. Jin-Peng Sun’s Lab since I graduated from Shandong University in 2012, and worked under the guidance of Prof. Sun as a postdoc/research associate/assistant professor. Since then, I have been working on dissecting the three-dimensional architecture and underlying molecular signaling mechanism of GPCR using cryo-electron microscopy (cryo-EM). So far, I have published 20 peer-reviewed papers as correspondence (or co- correspondence) or first (or co-first) authors, among which, four papers were published in Nature (2022a, 2022b, 2021, 2020); one paper was published in Cell (2021); on paper was published in Science (2023); two papers were published in Nat Chem Biol. (2022, 2018)." Peng Xiao on the web ResearchGate < Previous Session Next Session >

Full Agenda Adhesion GPCR workshop 2024 CINVESTAV, Mexico City, Mexico October 23-25 Download PDF Program HERE < Back to Full Agenda Session IV AGPCRs signaling in the nervous system BAI1/ADGRB1-mediated Regulation of Mitochondrial Morphology in Axons Joseph Duman Bai1 Is A Novel Neuronal Substrate Of The Psychiatric Risk Kinase TNIK Simeon R. Mihaylov Intricacies Of Complex Assembly And Ligand Interaction In The Adhesion GPCR Latrophilin/Cirl Anne Bormann BAI1/ADGRB1-mediated Regulation of Mitochondrial Morphology in Axons Joseph Duman Abstract Only available for AGPCR 24 Attendees Authors & Affiliations "Tolias, Kimberley F., Departments of Neuroscience and Biochemistry & Molecular Biology, Baylor College of Medicine, Houston, TX 77030" About Joseph Duman "Joseph Duman is an Assistant Professor in the Department of Neuroscience at Baylor College of Medicine, where he studies BAI1's role in the brain and the radiobiology of treatments for brain cancer. He trained at the University of California at Berkeley with John Forte and the University of Washington with Bertil Hille, before joining Kim Tolias' lab at Baylor College of Medicine." Joseph Duman on the web Baylor College of Medicine Kimberley Tolias Lab Bai1 Is A Novel Neuronal Substrate Of The Psychiatric Risk Kinase TNIK Simeon R. Mihaylov Abstract Only available for AGPCR 24 Attendees Authors & Affiliations "Flynn, Helen R.2, Sampedro-Castaneda, Marisol1, Claxton, Suzanne1, Skehel, Mark2, Ultanir, Sila K.1 1Kinases and Brain Development Laboratory, The Francis Crick Institute, UK 2Proteomics Science Technology Platform, The Francis Crick Institute, UK" About Simeon R. Mihaylov " I am a postdoctoral researcher in the kinases and brain development laboratory led by Dr Sila Ultanir at the Francis Crick Institute in London, England. I undertook my BSc in Biochemistry and Genetics at the University of Sheffield followed up by obtaining a PhD in molecular neuroscience at the Sheffield Institute for Translational Neuroscience. I then moved to King's College London, where my interest and passion for kinases in brain health and disease developed. I initially worked on mTOR in the pathogenesis of Tuberous Sclerosis Complex and then moved to the Francis Crick Institute working on the psychiatric risk kinase TNIK. I also work on multiple other kinases in our laboratory implicated in various neurodevelopmental and neurodegenerative disorders. My expertise includes biochemical approaches, proteomics and transcriptomics to name a few. I have recently also developed a strong interest in adhesion GPCRs and in particular, Bai1. " Simeon R. Mihaylov on the web Crick LinkedIn X (Twitter) Google Scholar Intricacies Of Complex Assembly And Ligand Interaction In The Adhesion GPCR Latrophilin/Cirl Anne Bormann Abstract Only available for AGPCR 24 Attendees Authors & Affiliations "Körner, Marek Benjamin; Dahse, Anne-Kristin; Ljaschenko, Dmitrij; Scholz, Nicole (Rudolf Schönheimer Institute of Biochemistry, Division of General Biochemistry, Faculty of Medicine, Leipzig University)" About Anne Bormann "I am a biochemist by training and studied at Leipzig University from 2015 to 2020. During my Bachelor's in 2018, I sought practical lab experience and found a position as a student assistant in Dr. Nicole Scholz's lab. My main topics were protein biochemistry, Drosophila husbandry, and genetics. I was fortunate that Nicole offered me an opportunity to do my Master's and later on a PhD thesis in her group. Since then, I have broadened my horizons with many more techniques in vivo and in vitro, with a main emphasis on the Adhesion GPCR Latrophilin/Cirl. Currently, I am in the final stages of my PhD, and I am looking forward to new projects and ideas." Anne Bormann on the web Rudolf-Schönheimer-Institut für Biochemie Scholz Lab < Previous Session Next Session >

Full Agenda Adhesion GPCR workshop 2024 CINVESTAV, Mexico City, Mexico October 23-25 Download PDF Program HERE < Back to Full Agenda Mexico City Nocturnal Tour, Food and drinks Coming Soon < Previous Session Next Session >

Home → Flash News → Science isn't always about eureka moments—sometimes it's about steady progress. In our latest Dr. GPCR Podcast episode, Ian Chronis shares his top aha moments, from learning the hard way about gel electrophoresis to discovering the hidden complexities of GPCR signaling. ✅ https://buff.ly/FTB69y9 #GPCR #DrGPCR #SciencePodcast #Pharmacology Published on April 22, 2025 Category Dr. GPCR Podcast Science isn't always about eureka moments—sometimes it's about steady progress. In our latest Dr. GPCR Podcast episode, Ian Chronis shares his top aha moments, from learning the hard way about gel electrophoresis to discovering the hidden complexities of GPCR signaling. ✅ https://buff.ly/FTB69y9 #GPCR #DrGPCR #SciencePodcast #Pharmacology Previous Next Recent Articles

Full Agenda Adhesion GPCR workshop 2024 CINVESTAV, Mexico City, Mexico October 23-25 Download PDF Program HERE < Back to Full Agenda Student Flash Presentations Health and Disease, Metabolism, Nervous System, Proteomics and Transcriptomics, Receptor Structure, Signaling and Activation Mechanism Adgrg6/Gpr126 is Required for Myocardial Notch Activity and N-cadherin Localization to Attain Trabecular Identity Abhishek Kumar Singh Investigating The Role of ADGRB3 Loss of Expression in Brain Tumor Formation in Li-Fraumeni Syndrome Alex Torrelli-Diljohn GPR124 Mediates Adhesion Of Leukemic Stem Cells To Their Niche And Leads To Myeloid Skewing Emmanouil Kyrloglou A single cell GPCR map of thermogenic fat Vasiliki Karagiannakou GAIN Domain Dynamics And Its Relevance For Adhesion GPCR Signaling In Vivo Lara-Sophie Brodmerkel Novel isoforms of adhesion G protein coupled receptor B1 (ADGRB1/BAI1) generated from an alternative promoter in intron 17 Rashed Rezwan Parag Identification of Differentially Expressed Gpr116 (Adgrf5) Transcript Variants in Mouse Kidney Hailey Steichen Elucidating The Role Of GPR97/ADGRG3 In Neutrophil Biology Tyler Bernadyn Next Generation MBD2 inhibitors for Brain Cancer Therapy Jesse Stillwell Adgrg6/Gpr126 is Required for Myocardial Notch Activity and N-cadherin Localization to Attain Trabecular Identity Abhishek Kumar Singh Abstract Only available for AGPCR 24 Workshop Attendees Authors & Affiliations "Srivastava, Swati1; Singh, Abhishek Kumar1; Gunawan, Felix2; Gentile, Alessandra2; Petersen, Sarah C.3; Stainier, Didier Y.R.2; Engel, Felix B.1 1 Experimental Renal and Cardiovascular Research, Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Kussmaulallee 12, 91054 Erlangen, Germany 2 Developmental Genetics, Max-Planck-Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany 3 Department of Developmental Biology, Washington University in St. Louis, 660 S. Euclid Ave, St. Louis, MO 63108, USA. Present address: Department of Neuroscience, Kenyon College, 203 North College Road, Gambier, OH 43022, USA" About Abhishek Kumar Singh "I am a doctoral student in the lab of Prof. Felix B. Engel. Since my undergraduate studies, I became fascinated with the class of adhesion GPCRs, owing to their potential, scarcity of knowledge on them, diverse expression profile, and the complexity with which they seem to be working. This made me pursue my higher education in the field of adhesion GPCRs. Accordingly, I worked with Prof. Hsi-Hsien Lin as summer intern twice, and finally joined the lab of Prof. Engel. I hope to develop my skillsets so as to be able to establish my own lab in future to work on adhesion GPCRs employing highly interdisciplinary field." Abhishek Kumar Singh on the web Uniklinikum Erlangen Google Scholar X (Twitter) Investigating The Role of ADGRB3 Loss of Expression in Brain Tumor Formation in Li-Fraumeni Syndrome Alex Torrelli-Diljohn Abstract "Li-Fraumeni syndrome (LFS) is a rare cancer predisposition syndrome caused by a germline mutation in the TP53 tumor suppressor gene. Glioblastoma (GBM) is the most prevalent central nervous system tumor in LFS, with TP53 mutations detected in 30% of sporadic GBMs. GBM is the most aggressive primary brain neoplasm that affects adults, with a median survival of 12-15 months. Recent studies implicate the dysregulation of adhesion G-Protein coupled receptors (GPCRs) in GBM development. Brain angiogenesis inhibitor 3 (BAI3/ADGRB3), a member of the BAI1-3 subfamily of adhesion GPCRS, has been observed to have low expression in brain tumors according to TCGA data, but the significance of this observation has not been explored. However, while its sister protein BAI1 has demonstrated tumor suppressor functions in the brain, it remains unclear whether BAI3 shares this role. To test this, an LFS mouse model (germline Tp53 deletion) with a second floxed allele under the control of Nestin-Cre was crossed to Bai3-/- mice. Preliminary findings indicate that the simultaneous loss of Bai3 and Tp53 expression in our mouse model increased spontaneous brain tumor formation incidence from 34% to 71%, in contrast to the loss of p53 alone. These observations lead me to hypothesize that ADGRB3 functions as a tumor suppressor in the brain, and its silencing, in the context of p53 mutation, facilitates GBM formation. Isolated GBM stem cells were collected for further genomic analyses and to test whether overexpression of BAI3 will save the tumor phenotype." Authors & Affiliations "Vukadin L, Park B, Mohamed M, Li H, Elkholy A, Torrelli-Diljohn A, Kim JH, Jeong K, Murphy JM, Harvey CA, Dunlap S, Gehrs L, Lee H, Kim HG, Sah JP, Lee SN, Stanford D, Barrington RA, Foote JB, Sorace AG, Welner RS, Hildreth BE 3rd, Lim SS, Ahn EE. A mouse model of Zhu-Tokita-Takenouchi-Kim syndrome reveals indispensable SON functions in organ development and hematopoiesis. JCI Insight. 2024 Mar 8;9(5):e175053. doi: 10.1172/jci.insight.175053. PMID: 38290089; PMCID: PMC10972584. University of Alabama at Birmingham" About Alex Torrelli-Diljohn "Alex completed his undergraduate & master’s degrees in Neurobiology & Cognitive sciences from the University of South Florida, where he researched early-onset Alzheimer’s disease in the lab of Dr. Angele Parent. He is interested in working on Li-Fraumeni syndrome and helping patients afflicted with this condition. He is also interested in working on Glioma Brain Organoid models." Alex Torrelli-Diljohn on the web The University of Alabama at Birmingham LinkedIn GPR124 Mediates Adhesion Of Leukemic Stem Cells To Their Niche And Leads To Myeloid Skewing Emmanouil Kyrloglou Abstract Only available for AGPCR 24 Workshop Attendees About Emmanouil Kyrloglou "Studied medicine at the University of Groningen. Now PhD-candidate at the Experimental Hematology lab of the University Medical Center Groningen (UMCG)." Emmanouil Kyrloglou on the web Adhesion GPCR Consortium LinkedIn A single cell GPCR map of thermogenic fat Vasiliki Karagiannakou Abstract Only available for AGPCR 24 Workshop Attendees Authors & Affiliations "Karagiannakou Vasiliki, El Merahbi Rabih, Herzig Stephan , Georgiadi A , Helmholtz Center Munich, Institute of Diabetes and Cancer" About Vasiliki Karagiannakou "MSc in Bioinformatics, PhD student since 2022 in the Institute for Diabetes and Cancer IDC, Helmholtz Centre Munich" Vasiliki Karagiannakou on the web Helmholtz Centre Munich GAIN Domain Dynamics And Its Relevance For Adhesion GPCR Signaling In Vivo Lara-Sophie Brodmerkel Abstract "Over the last years, Adhesion G Protein-coupled receptors (aGPCR) have been shown to play a crucial role in the perception of mechanical signals. However, the molecular details underlying their activation and how mechanical forces are translated into an intracellular response remains largely unknown. Recent Molecular Dynamics (MD) simulations of several aGPCRs predicted two flexible regions, termed flaps, located within the GPCR autoproteolysis inducing (GAIN) domain. These flaps could theoretically enable partial decryption of the Stachel through lateral movement and affect activation of the receptor independent of NTF-CTF dissociation. However, the physiological relevance of flap flexibility on receptor activation and signaling remains unclear. To investigate whether flexibility of GAIN flaps affects aGPCR function under native conditions, we strategically inserted specific mutations into the GAIN domain of the Latrophilin homologue Cirl in Drosophila melanogaster, with the intention to alter flap dynamics. Our goal is to understand if and how flap dynamics influence Cirl function and consequently the mechanosensory faculty of neurons in vivo. To this end, we combine behavioral, biochemical, immunohistochemical and functional readouts, with the overarching ambition to expand our knowledge on the mechanistic details underlying aGPCR activation in mechanosensation." Authors & Affiliations "Brodmerkel Lara-Sophie 1, Bormann Anne 1, Seufert Florian 2, Hildebrand Peter 2,3 ´, Ljaschenko Dmitrij 1´, Scholz Nicole 1´ 1Rudolf Schönheimer Institute of Biochemistry, Division of General Biochemistry, Medical Faculty, Leipzig University, Leipzig, Germany 2Institute for Medical Physics and Biophysics, Medical Faculty, Leipzig University, Leipzig, Germany 3Institute of Medical Physics and Biophysics, Charité – Universitätsmedizin Berlin, Berlin, Germany ´ correspondence: scholzlab@gmail.com , Dmitrij.Ljaschenko@medizin.uni-leipzig.de , peter.hildebrand@medizin.uni-leipzig.de *contributed equally" About Lara-Sophie Brodmerkel "I am a medical student and I´m currently working on my MD thesis in the lab of Dr. Nicole Scholz. We are investigating the relevance of GAIN domain dynamics for aGPCR signaling in Drosophila melanogaster." Lara-Sophie Brodmerkel on the web University of Leipzig Novel isoforms of adhesion GPCR B1 (ADGRB1/BAI1) generated from an alternative promoter in intron 17 Rashed Rezwan Parag Abstract "Brain-specific angiogenesis inhibitor 1 (BAI1) belongs to the adhesion G-protein-coupled receptors, which exhibit large multi-domain extracellular N-termini that mediate cell-cell and cell-matrix interactions. To explore the existence of BAI1 isoforms, we queried genomic datasets for markers of active chromatin and new transcript variants in the ADGRB1 (adhesion G protein-coupled receptor B1) gene. Two major types of mRNAs were identified in human/mouse brain, those with a start codon in exon 2 encoding a full-length protein of a predicted size of 173.5/173.3 kDa and shorter transcripts starting from alternative exons at the intron 17/exon 18 boundary with new or exon 19 start codons, predicting shorter isoforms of 76.9/76.4 and 70.8/70.5 kDa, respectively. Immunoblots on wild-type and Adgrb1 exon 2-deleted mice, reverse transcription PCR and promoter-luciferase reporters confirmed that the shorter isoforms originate from an alternative promoter in intron 17. The shorter BAI1 isoforms lack most of the N-terminus and are very close in structure to the truncated BAI1 isoform generated through GPS processing from the full-length receptor. The cleaved BAI1 isoform has a 19 amino acid extracellular stalk that can serve as a receptor agonist, while the alternative transcripts generate BAI1 isoforms with extracellular N-termini of 5 or 60 amino acids. Further studies are warranted to compare the functions of these isoforms and examine the distinct roles they play in different tissues and cell types." About Rashed Rezwan Parag "Rashed is from Bangladesh. He has received his BSc and MS degree from the Department of Biochemistry and Molecular Biology, University of Chittagong, Bangladesh. Before joining UAB as a graduate student, he worked in the EuGEF Research Group to identify novel prognostic biomarkers and therapeutic options for Metastatic Breast Cancer (BC) and Head and Neck Squamous Cell Carcinoma (HNSCC). Currently, he is working to elucidate the role of ADGRB1 and ADGRB3 in medulloblastoma (pediatric brain tumor)." Rashed Rezwan Parag on the web Google Scholar Identification of Differentially Expressed Gpr116 (Adgrf5) Transcript Variants in Mouse Kidney Hailey Steichen Abstract "Adhesion G protein-coupled receptors (aGPCRs) are important and understudied modulators of physiological processes. Previous work suggests that aGPCRs, and Adgrf5 in particular, undergo significant tissue-specific mRNA processing that results in holoreceptors with unique and variable N-terminal structures (Knierim et al. 2019). Recently, it was shown that transcripts of the postsynaptic aGPCR Latrophilin-3 (Lphn3/Adgrl3) undergo physiologically relevant alternative splicing, which determined heterotrimeric signaling through Gαs- or Gα12/13- mediated pathways (Südhof et al. 2024). These results demonstrate that identifying precise, tissue-specific transcript variants is critical to understanding the physiological relevance of aGPCRs. Moreover, these studies highlight the possibility that tissue expression of single aGPCRs is likely comprised of multiple transcript variants. We previously demonstrated that kidney-specific Adgrf5/Gpr116 knockout causes luminal membrane accumulation of V-ATPase in acid-secreting A-type intercalated cells (AICs) in the collecting ducts and a significant reduction in urine pH (Zaidman et al. 2020). Renal Adgrf5 is restricted to two distinct populations of cells: AICs and endothelial cells (ECs). We hypothesized that cell-specific Adgrf5 transcript variants are expressed in renal AICs and ECs, and therefore are activated by distinct mechanisms unique to the cellular microenvironment. We detected and aligned three Adgrf5 exons that undergo differential expression in the kidney: exons 2, 12, and 22. Adgrf5 transcripts in FACS-sorted GFP+ ICs do not contain the exon 2 variable region, or the alternative exons 12 and 22, while ECs contain all three. However, EC markers were detected in GFP+ ICs, demonstrating some EC contamination in the sorted ICs. Detection of transcripts that do, and do not, contain multiple variable regions suggests expression of multiple mRNAs in specific cells. These data demonstrate that Adgrf5 transcript variants are cell-specific in the kidney. Moreover, the complete repertoire of aGPCRs expressed in the kidney is undefined. We performed single-nucleus RNA sequencing on male and female kidneys. snRNAseq revealed abundant, cell-specific expression of six aGPCRs (Adgrl4, Adgre5, Adgrf1, Adgrf5, Adgrg1, and Adgrg3). Detection of these, as well as 18 other aGPCRs, was confirmed by PCR screening for GAIN/GPS domains on cDNA from whole-kidney lysates. These results reveal the complete set of aGPCRs expressed in the murine kidney. Future studies will focus on determining the physiological roles and tissue-specific variants of these receptors." Authors & Affiliations "Department of Biochemistry & Molecular Biology, University of New Mexico Health Sciences Center Xue, Jianxiang; Yan, Teagan; Eaton, Krystin, and Zaidman, Nathan" About Hailey Steichen "I currently work in Dr. Nathan Zaidman’s lab at the University of New Mexico Health Sciences Center. I am researching the physiological relevance of Adgrf5 (Gpr116) transcript variants in specific cell types in the kidney. I have also worked in the laboratory of Dr. James Bridges at National Jewish Health in Denver, CO researching molecular mechanisms of lung injury and repair mediated by Adgrf5. I received my MS in Applied Toxicology from the University of Washington, and my BA in Biology from Vassar College." Hailey Steichen on the web Zaidman Physiology Lab Elucidating The Role Of GPR97/ADGRG3 In Neutrophil Biology Tyler Bernadyn Abstract Only available for AGPCR 24 Workshop Attendees Authors & Affiliations "Gandhi, Riya; Chandan, Nancy; Kwarcinski, Frank; Smrcka, Alan; and Tall, Gregory G." About Tyler Bernadyn "4th year Pharmacology Ph.D. Student in Greg Tall's Lab." Tyler Bernadyn on the web LinkedIn Next Generation MBD2 inhibitors for Brain Cancer Therapy Jesse Stillwell Abstract "Medulloblastoma (MB) is one of the most lethal pediatric brain tumors. Standard of care for MB includes tumor resection, chemotherapy, and cranio-spinal radiation. This regimen has long lasting side-effects, including neuroendocrine and cognitive problems, and ~ 30% of patients still do not survive 5 years past diagnosis. Clearly, a new, less toxic therapeutic is needed. Our lab has previously shown that expression of adhesion GPCR BAI1 (ADGRB1) is lost by epigenetic silencing in MB. Restoration of ADGRB1 expression slowed tumor growth and improved survival in mice bearing MB xenografts. The ADGRB1 promoter is methylated in MB, and this allows for Methyl CpG Binding Domain protein 2 (MBD2) to silence the gene through recruitment of the NuRD silencing complex. KCC-07 is an inhibitor that prevents MBD2 from binding to DNA, allowing re-expression of BAI1. To further optimize the chemical scaffold, we synthesized KCC07 analogs that we’re testing for their ability to reactivate BAI1 expression. The current methods for testing KCC-07’s ability to reactivate ADGRB1 expression involve western blotting and RT-qPCR, both of which are semi-quantitative methods that require large numbers of cells and high volumes of analogs, creating a bottleneck in screening. These methods are time consuming, and their inherent variability makes precise quantification difficult. This research focuses on the design of a new endogenous ADGRB1 activation reporter assay to test analogs faster and with more reproducibility." Authors & Affiliations "Erwin Van Meir, University of Alabama at Birmingham/Sadanandan Velu, University of Alabama at Birmingham/Takahiro Yamamoto, Kumamoto University" About Jesse Stillwell "Jesse Stillwell is a 3rd year graduate student with a research focus in drug development. His project is drug discovery focused, with particular interest in use of a novel epigenetic therapy to reactivate ADGRB1 expression." Jesse Stillwell on the web Van Meir Lab – Heersink School of Medicine < Previous Session Next Session >

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Full Agenda Adhesion GPCR workshop 2024 CINVESTAV, Mexico City, Mexico October 23-25 Download PDF Program HERE < Back to Full Agenda Welcoming Remarks < Previous Session Next Session >

Full Agenda Adhesion GPCR workshop 2024 CINVESTAV, Mexico City, Mexico October 23-25 Download PDF Program HERE < Back to Full Agenda Session IX / Technology capsule: Light on aGPCR signaling and function NovoiSMART - A new platform for GPCR antibody drug discovery Abstract Developing monoclonal antibody drugs against GPCRs and other multi-pass transmembrane targets, such as ion channels, remains a significant challenge. Novoprotein developed a NovoiSMART technology, utilizing mRNA-based immunization, which can overcome these obstacles by producing high-quality antibodies that more accurately mimic natural protein structures. This approach contrasts with other antigen forms like peptides or DNA, which face limitations in structural integrity and immunogenicity. mRNA technology, demonstrated in the success of COVID-19 vaccines, is emerging as a promising method for antibody discovery. Several case studies of GPCR and other multi-pass transmembrane targets are presented, including GPRC5D, Claudin 6 and Napi2b. These studies show that mRNA immunization yields higher antibody titers and greater epitope diversity compared to other methods. These examples underscore the potential of NovoiSMART technology in developing highly specific antibodies for complex targets, with implications for overcoming challenges like drug resistance and tumor escape. About Gavin Zhang Gavin is a currently a director of business and operations at Novoprotein Scientific. His research experience includes phylogenetics and cancer epigenetics. Gavin Zhang on the web LinkedIn < Previous Session Next Session >

Home → Flash News → “Research is all about knowing when to walk and when to run.” –Ben Clements In Ep. 166 of the Dr.GPCR Podcast, hear how a postdoc is reshaping the conversation on opioid use, imposter syndrome, and the power of collaborative science. Why early-career voices are critical in GPCR drug discovery —and how lab culture makes all the difference. 🎧 Watch here: https://buff.ly/Kr3qKud #GPCRresearch #DrGPCR #GPCRpodcast #OpioidPharmacology #DrugDiscovery Published on May 20, 2025 Category Dr. GPCR Podcast “Research is all about knowing when to walk and when to run.” –Ben Clements In Ep. 166 of the Dr.GPCR Podcast, hear how a postdoc is reshaping the conversation on opioid use, imposter syndrome, and the power of collaborative science. Why early-career voices are critical in GPCR drug discovery —and how lab culture makes all the difference. 🎧 Watch here: https://buff.ly/Kr3qKud #GPCRresearch #DrGPCR #GPCRpodcast #OpioidPharmacology #DrugDiscovery Previous Next Recent Articles

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Full Agenda Adhesion GPCR workshop 2024 CINVESTAV, Mexico City, Mexico October 23-25 Download PDF Program HERE < Back to Full Agenda Session III Molecular tools and biosensors directed at AGPCR signaling and function The NTF Release Sensor Approach for Drug Discovery for Human Adhesion GPCRs Stephanie Häfner bioSens-All: A Multiparametric BRET-Based Platform for Comprehensive Profiling of adhesion GPCR Signaling and Pharmacology-Enabling Drug Discovery Laurent Sabbagh Characterizing hADGRE5/CD97 Activation and Signaling: A Mechanical Stimulation BRET-Based Approach (MS-BRET) Ana Lilia Moreno Salinas The NTF Release Sensor Approach for Drug Discovery for Human Adhesion GPCRs Stephanie Häfner Abstract "G Protein-coupled receptors (GPCRs) are common drug targets, yet no approved drugs exist for the Adhesion G Protein-coupled receptors (aGPCRs or ADGRs). This gap is due to their unique autoproteolytic cleavage in the GAIN domain, creating a heterodimer of an N-terminal fragment (NTF) and a C-terminal fragment (CTF), posing challenges for traditional drug discovery. To address this, we developed the NTF release sensor (NRS), a genetically encoded reporter that facilitates visualization and quantification of aGPCR NTF-CTF separation events both in vitro and in vivo. The NRS fuses the extracellular region of any given aGPCR with a cleavage module from a Notch receptor. Upon NTF dissociation, an intracellular transcription factor (reporter module) is released, generating a specific, measurable biochemical signal. The NRS system has recently been validated in vivo by targeting the latrophilin-type aGPCR Cirl/ADGRL in Drosophila, revealing NTF release and receptor dissociation within the developing nervous system. It was then adapted for the human aGPCRs CD97/ADGRE5 and Latrophilin/ADGRL3 and tested in HEK293T cells using a luciferase assay to detect NTF release events. After validating the functionality of the NRS and demonstrating its utility for monitoring aGPCR dissociation across different species, we plan to adapt this technology for high-throughput screening of pharmacological compound libraries to identify potential therapeutic substances for aGPCRs. By leveraging self-cleavage and NTF release, the NRS technology offers a novel approach distinct from conventional GPCR drug discovery methods. This tailored system aims to expedite the identification of drugs targeting the unique aGPCR receptor family and customize the method for disease-relevant human aGPCRs." Authors & Affiliations "Dahse, Anne-Kristin; Annadurai, Prabakaran; Demirbaş, Berkay; Kemkemer, Marguerite; Langenhan, Tobias; Scholz, Nicole Rudolf Schönheimer Institute of Biochemistry, Divison of General Biochemistry, Medical Faculty, Leipzig University, Leipzig, Germany" About Stephanie Häfner "I am a trained chemist with extensive biochemical experience. After earning my Master of Science in Chemistry, I pursued my PhD in Dr. Michael Schaefer’s group at Leipzig University, Germany, focusing on drug screening and utilizing electrophysiological and imaging techniques to study TRP ion channels. Immediately following my PhD, I joined Dr. Guillaume Sandoz's group in 2019 as a postdoctoral research scientist at Université Côte d‘Azur, France. There, I investigated Two-Pore-Potassium channels using electrophysiology, molecular and chemical biology techniques, and fluorescence imaging. In 2021, I joined Dr. Tobias Langenhan's group, where I currently manage a project to establish a drug screening assay for Adhesion GPCRs using a specialized sensor system and mentor PhD students." Stephanie Häfner on the web LinkedIn Scholz Lab Langenhan Lab bioSens-All: A Multiparametric BRET-Based Platform for Comprehensive Profiling of adhesion GPCR Signaling and Pharmacology-Enabling Drug Discovery Laurent Sabbagh Abstract "The 3rd generation bioSens-All platform combines BRET-based biosensors that are highly adaptable to the needs of discovery projects for small molecules, peptides, and antibodies. The platform has been successfully used internally to identify biased small molecule negative allosteric modulators for protease-activated receptor 2 (PAR2). The platform revealed different mechanisms-of-action of our lead compound when benchmarked against other antagonists of PAR2. In addition, the platform was used to develop assays for high-throughput screening for challenging adhesion GPCRs. These examples will demonstrate how the bioSens-All platform was used to advance projects from discovery to preclinical candidate nomination and to provide the tools to advance adhesion GPCR biology." Authors & Affiliations "Ana Lilia Moreno Salinas (2), Arturo Mancini (1), Raida Jallouli (2), Richard Leduc (2) (1)Domain Therapeutics North America Inc, Montréal, Québec, Canada (2) Department of Pharmacology-Physiology, Université de Sherbrooke, Québec, Canada" About Laurent Sabbagh "Laurent holds a Ph.D. in immunology from McGill University. Following his doctoral degree Dr. Sabbagh undertook post-doctoral fellowships at the Ontario Cancer Institute and the University of Toronto before being recruited by University of Montreal as an assistant professor working on the role of TNF receptors in immunological memory, inflammation and hematological malignancies. In the fall of 2013, Dr. Sabbagh was recruited by Vertex Pharmaceuticals (Canada) where he worked on biomarker discovery for inflammatory bowel disease and small molecules drug discovery for polycystic kidney disease. Subsequently, Dr. Sabbagh led research projects aimed on drug discovery of small molecules for the treatment of inflammatory disorders and cancer at Paraza Pharma Inc. in Montreal. Laurent is currently leading DTNA discovery group working on GPCRs in immuno-oncology to discover new molecules and antibodies." Laurent Sabbagh on the web Domain Therapeutics Characterizing hADGRE5/CD97 Activation and Signaling: A Mechanical Stimulation BRET-Based Approach (MS-BRET) Ana Lilia Moreno Salinas Abstract Only available for AGPCR 24 Attendees Authors & Affiliations "Arturo Mancini (2), Samya Aouad (2,3), Herthana Kandasamy (2), Sandra Morrissette (2), Arhamatoulaye Maiga (4), Michel Bouvier (4), Richard Leduc (1), Laurent Sabbagh (2) 1. Department of Pharmacology-Physiology, Université de Sherbrooke, Sherbrooke, Quebec, Canada 2. Domain Therapeutics North America Inc., Montreal, Quebec, Canada 3. Université Claude Bernard - Lyon, Faculté de Pharmacie, Lyon, France 4. Department of Biochemistry and Molecular Medicine, Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montreal, Quebec, Canada " About Ana Lilia Moreno Salinas "I am currently part of a dynamic research team dedicated to advancing the understanding of G protein-coupled receptors (GPCRs), with a particular focus on the adhesion GPCRs (aGPCRs) family. My expertise lies in exploring the biological properties and signaling pathways activated by aGPCRs, investigating their roles in both normal physiological and pathological conditions. Our research aims to leverage this knowledge to identify novel pharmacological targets and contribute to the development of innovative treatments for a range of diseases, including psychiatric disorders and cancer." Ana Lilia Moreno Salinas on the web ResearchGate LinkedIn < Previous Session Next Session >