< GPCR News < GPCRs in Oncology and Immunology Expression pattern and clinical significance of beta 2-adrenergic receptor in oral squamous cell carcinoma: an emerging prognostic indicator and future therapeutic target Published date November 1, 2022 Abstract Purpose: Beta 2-Adrenergic Receptor (β2-AR) is significantly overexpressed in various types of malignancies, which is associated with the worst prognosis. However, the role of β2-AR in oral cancer is not well identified. The present study aimed at investigating the β2-AR gene expression and its significance in relation with the clinicopathological features and overall survival of oral squamous cell carcinoma (OSCC) patients. Methods: Immunohistochemistry, western blot and quantitative real-time PCR techniques were used to analyze β2-AR protein and mRNA levels in a total of 65 histopathologically confirmed OSCC tissues (case group) and 65 normal tissues (control group) from the oral cavity. Results: Out of the total of 65 OSCC tissues, 41 tissues (63.1%) exhibited high expression for β2-AR protein. Percent positivity and relative density (mean ± SD) of protein were higher in the case group as compared to the control group (positivity 40.31 ± 3.01 vs. 20.46 ± 1.93, p < 0.001; density 2.77 ± 1.17 vs. 1.28 ± 0.37, p < 0.001). In addition, β2-AR mRNA level was also upregulated in patients compared to the controls (2.36 ± 1.30 vs. 1.09 ± 0.42, p < 0.001) and showed a positive correlation with immunostaining of protein in OSCC (r = 0.48, p = 0.011). High β2-AR protein expression was significantly associated with multiple risk habits (p = 0.045), histological differentiation (p = 0.013), clinical TNM stages (p = 0.014), and poor survival (p = 0.006) of patients. In the Cox proportional hazards model, β2-AR was identified as a prognostic biomarker of OSCC (p = 0.047). Conclusion: β2-AR protein level is identified as an independent significant prognostic factor in patients with oral carcinoma. Authors Akhilesh Krishna, Vineeta Singh, Nishtha Singh, Shraddha Singh, Sujit Kumar Mohanty, Rajender Singh, Vijay Kumar, Uma Shankar Singh, Rakesh Kumar Singh Tags GPCR; OSCC; Oral cancer; Prognostic factor; β2-Adrenergic Receptor. Source Contribute to the GPCR News Coming soon Become a Contributor Classified GPCR News Call for GPCR papers GPCR Industry News Adhesion GPCRs GPCR Events, Meetings, and Webinars Reviews, GPCRs, and more GPCR Binders, Drugs, and more Methods & Updates in GPCR Research GPCRs in Neuroscience GPCRs in Cardiology, Endocrinology, and Taste GPCRs in Oncology and Immunology Structural and molecular insights into GPCR function GPCR Activation and Signaling More from Dr. GPCR Create an account and get our contributors articles in your inbox Subscribe to the Dr. GPCR Monthly Newsletter today! Follow the Dr. GPCR News and get weekly notifications about the GPCR field Share < Previous Next >

Dr. GPCR Podcast << Back to podcast list 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 Thanks for listening to this podcast episode This short survey will help us understand your needs to bring you exciting and informative content; this short survey should take 5 minutes to fill. Listen and subscribe to where you get your podcasts. << Previous Podcast Episode Next Podcast Episode >>

Dr. GPCR Podcast << Back to podcast list 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 Thanks for listening to this podcast episode This short survey will help us understand your needs to bring you exciting and informative content; this short survey should take 5 minutes to fill. Listen and subscribe to where you get your podcasts. << Previous Podcast Episode Next Podcast Episode >>

< GPCR News < GPCRs in Oncology and Immunology Functional Assessment of Cancer-Linked Mutations in Sensitive Regions of Regulators of G Protein Signaling Predicted by Three-Dimensional Missense Tolerance Ratio Analysis Published date January 1, 2023 Abstract Regulators of G protein signaling (RGS) proteins modulate G protein-coupled receptor (GPCR) signaling by acting as negative regulators of G proteins. Genetic variants in RGS proteins are associated with many diseases, including cancers, although the impact of these mutations on protein function is uncertain. Here we analyze the RGS domains of 15 RGS protein family members using a novel bioinformatic tool that measures the missense tolerance ratio (MTR) using a three-dimensional (3D) structure (3DMTR). Subsequent permutation analysis can define the protein regions that are most significantly intolerant ( P < 0.05) in each dataset. We further focused on RGS14, RGS10, and RGS4. RGS14 exhibited seven significantly tolerant and seven significantly intolerant residues, RGS10 had six intolerant residues, and RGS4 had eight tolerant and six intolerant residues. Intolerant and tolerant-control residues that overlap with pathogenic cancer mutations reported in the COSMIC cancer database were selected to define the functional phenotype. Using complimentary cellular and biochemical approaches, proteins were tested for effects on GPCR-G α activation, G α binding properties, and downstream cAMP levels. Identified intolerant residues with reported cancer-linked mutations RGS14-R173C/H and RGS4-K125Q/E126K, and tolerant RGS14-S127P and RGS10-S64T resulted in a loss-of-function phenotype in GPCR-G protein signaling activity. In downstream cAMP measurement, tolerant RGS14-D137Y and RGS10-S64T and intolerant RGS10-K89M resulted in change of function phenotypes. These findings show that 3DMTR identified intolerant residues that overlap with cancer-linked mutations cause phenotypic changes that negatively impact GPCR-G protein signaling and suggests that 3DMTR is a potentially useful bioinformatics tool for predicting functionally important protein residues. SIGNIFICANCE STATEMENT: Human genetic variant/mutation information has expanded rapidly in recent years, including cancer-linked mutations in regulator of G protein signaling (RGS) proteins. However, experimental testing of the impact of this vast catalogue of mutations on protein function is not feasible. We used the novel bioinformatics tool three-dimensional missense tolerance ratio (3DMTR) to define regions of genetic intolerance in RGS proteins and prioritize which cancer-linked mutants to test. We found that 3DMTR more accurately classifies loss-of-function mutations in RGS proteins than other databases thereby offering a valuable new research tool. Authors Carolina Montañez-Miranda , Riley E Perszyk , Nicholas H Harbin , Jennifer Okalova , Suneela Ramineni , Stephen F Traynelis , John R Hepler Source Contribute to the GPCR News Coming soon Become a Contributor Classified GPCR News Call for GPCR papers GPCR Industry News Adhesion GPCRs GPCR Events, Meetings, and Webinars Reviews, GPCRs, and more GPCR Binders, Drugs, and more Methods & Updates in GPCR Research GPCRs in Neuroscience GPCRs in Cardiology, Endocrinology, and Taste GPCRs in Oncology and Immunology Structural and molecular insights into GPCR function GPCR Activation and Signaling More from Dr. GPCR Create an account and get our contributors articles in your inbox Subscribe to the Dr. GPCR Monthly Newsletter today! Follow the Dr. GPCR News and get weekly notifications about the GPCR field Share < Previous Next >

< GPCR News < GPCRs in Oncology and Immunology Ultrasensitive dose-response for asbestos cancer risk implied by new inflammation-mutation model Published date August 1, 2023 Abstract "Alterations in complex cellular phenotype each typically involve multistep activation of an ultrasensitive molecular switch (e.g., to adaptively initiate an apoptosis, inflammasome, Nrf2-ARE anti-oxidant, or heat-shock activation pathway) that triggers expression of a suite of target genes while efficiently limiting false-positive switching from a baseline state. Such switches exhibit nonlinear signal-activation relationships. In contrast, a linear no-threshold (LNT) dose-response relationship is expected for damage that accumulates in proportion to dose, as hypothesized for increased risk of cancer in relation to genotoxic dose according to the multistage somatic mutation/clonal-expansion theory of cancer, e.g., as represented in the Moolgavkar-Venzon-Knudsen (MVK) cancer model by a doubly stochastic nonhomogeneous Poisson process. Mesothelioma and lung cancer induced by exposure to carcinogenic (e.g., certain asbestos) fibers in humans and experimental animals are thought to involve modes of action driven by mutations, cytotoxicity-associated inflammation, or both, rendering ambiguous expectations concerning the nature of model-implied shape of the low-dose response for above-background increase in risk of incurring these endpoints. A recent Inflammation Somatic Mutation (ISM) theory of cancer posits instead that tissue-damage-associated inflammation that epigenetically recruits, activates and orchestrates stem cells to engage in tissue repair does not merely promote cancer, but rather is a requisite co-initiator (acting together with as few as two somatic mutations) of the most efficient pathway to any type of cancer in any reparable tissue (Dose-Response 2019; 17(2):1-12). This theory is reviewed, implications of this theory are discussed in relation to mesothelioma and lung cancer associated with chronic asbestos inhalation, one of the two types of ISM-required mutations is here hypothesized to block or impede inflammation resolution (e.g., by doing so for GPCR-mediated signal transduction by one or more endogenous autacoid specialized pro-resolving mediators or SPMs), and supporting evidence for this hypothesis is discussed." Author Kenneth T Bogen Tags Asbestos , Cytotoxicity , Inflammation , Lung cancer , Mesothelioma , Mutation Source Contribute to the GPCR News Coming soon Become a Contributor Classified GPCR News Call for GPCR papers GPCR Industry News Adhesion GPCRs GPCR Events, Meetings, and Webinars Reviews, GPCRs, and more GPCR Binders, Drugs, and more Methods & Updates in GPCR Research GPCRs in Neuroscience GPCRs in Cardiology, Endocrinology, and Taste GPCRs in Oncology and Immunology Structural and molecular insights into GPCR function GPCR Activation and Signaling More from Dr. GPCR Create an account and get our contributors articles in your inbox Subscribe to the Dr. GPCR Monthly Newsletter today! Follow the Dr. GPCR News and get weekly notifications about the GPCR field Share < Previous Next >

Dr. GPCR Podcast << Back to podcast list 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 Thanks for listening to this podcast episode This short survey will help us understand your needs to bring you exciting and informative content; this short survey should take 5 minutes to fill. Listen and subscribe to where you get your podcasts. << Previous Podcast Episode Next Podcast Episode >>

Dr. GPCR Podcast << Back to podcast list Dr. Graciela Pineyro 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 Thanks for listening to this podcast episode This short survey will help us understand your needs to bring you exciting and informative content; this short survey should take 5 minutes to fill. Listen and subscribe to where you get your podcasts. << Previous Podcast Episode Next Podcast Episode >>

Dr. GPCR Podcast << Back to podcast list Annabelle Milner About Annabelle Milner Annabelle completed her undergraduate degree in Biomedical Sciences at the University of Bath. As part of the degree, she undertook a 1-year research-based placement at the Charles Perkins Centre in Sydney, investigating the effects of dietary carbohydrates on metabolic health with Dr. Jibran Wali. From here, she returned to the UK. She began her Ph.D. at Imperial College London with Prof Aylin Hanyaloglu, Prof Gary Frost, and Dr. Alastair Brown (Sosei Heptares), where she is currently a final year Ph.D. student. Annabelle’s Ph.D. work focuses on microbial-derived metabolites that signal through GPCRs expressed in the GI. In particular, she is looking at L- and D-lactate-activated HCAR1 signaling. She presented her Ph.D. work at the Society of Endocrinology Conference 2022 and was awarded the best oral poster prize. Outside the lab, she enjoys baking and swimming and has recently taken up paddle boarding. Annabelle Milner on the web Linkedin Researchgate Pubmed Dr. GPCR Thanks for listening to this podcast episode This short survey will help us understand your needs to bring you exciting and informative content; this short survey should take 5 minutes to fill. Listen and subscribe to where you get your podcasts. << Previous Podcast Episode Next Podcast Episode >>

< GPCR News < GPCRs in Oncology and Immunology Role and recent progress of P2Y12 receptor in cancer development Published date June 14, 2024 Abstract "P2Y12 receptor (P2Y12R) is an adenosine-activated G protein-coupled receptor (GPCR) that plays a central role in platelet function, hemostasis, and thrombosis. P2Y12R activation can promote platelet aggregation and adhesion to cancer cells, promote tumor angiogenesis, and affect the tumor immune microenvironment (TIME) and tumor drug resistance, which is conducive to the progression of cancers. Meanwhile, P2Y12R inhibitors can inhibit this effect, suggesting that P2Y12R may be a potential therapeutic target for cancer. P2Y12R is involved in cancer development and metastasis, while P2Y12R inhibitors are effective in inhibiting cancer. However, a new study suggests that long-term use of P2Y12R inhibitors may increase the risk of cancer and the mechanism remains to be explored. In this paper, we reviewed the structural and functional characteristics of P2Y12R and its role in cancer. We explored the role of P2Y12R inhibitors in different tumors and the latest advances by summarizing the basic and clinical studies on the effects of P2Y12R inhibitors on tumors." Authors Yanni Xi, Zhenya Min, Mianxue Liu, Xueqin Li, Zhao-Hua Yuan Tags P2Y12R , P2Y12R inhibitors , Platelets , Tumor , Tumor microenvironment Source Contribute to the GPCR News Coming soon Become a Contributor Classified GPCR News Call for GPCR papers GPCR Industry News Adhesion GPCRs GPCR Events, Meetings, and Webinars Reviews, GPCRs, and more GPCR Binders, Drugs, and more Methods & Updates in GPCR Research GPCRs in Neuroscience GPCRs in Cardiology, Endocrinology, and Taste GPCRs in Oncology and Immunology Structural and molecular insights into GPCR function GPCR Activation and Signaling More from Dr. GPCR Create an account and get our contributors articles in your inbox Subscribe to the Dr. GPCR Monthly Newsletter today! Follow the Dr. GPCR News and get weekly notifications about the GPCR field Share < Previous Next >

Dr. GPCR Podcast << Back to podcast list Dr. Aylin Hanyaloglu 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 Researchgate Twitter Imperial College London Elsevier Loop Dr. GPCR Ecosystem Thanks for listening to this podcast episode This short survey will help us understand your needs to bring you exciting and informative content; this short survey should take 5 minutes to fill. Listen and subscribe to where you get your podcasts. << Previous Podcast Episode Next Podcast Episode >>

< Back 10/25/2024 [object Object] ​ Previous Next

< GPCR News < GPCRs in Oncology and Immunology Glucose and HODEs regulate Aspergillus ochraceus quorum sensing through the GprC-AcyA pathway Published date May 29, 2024 Abstract "Aspergillus ochraceus is the traditional ochratoxin A (OTA)-producing fungus with density-dependent behaviors, which is known as quorum sensing (QS) that is mediated by signaling molecules. Individual cells trend to adapt environmental changes in a "whole" flora through communications, allowing fungus to occupy an important ecological niche. Signals perception, transmission, and feedback are all rely on a signal network that constituted by membrane receptors and intracellular effectors. However, the interference of density information in signal transduction, which regulates most life activities of Aspergillus, have yet to be elucidated. Here we show that the G protein-coupled receptor (GPCR) to cAMP pathway is responsible for transmitting density information, and regulates the key point in life cycle of A. ochraceus. Firstly, the quorum sensing phenomenon of A. ochraceus is confirmed, and identified the density threshold is 103 spores/mL, which represents the low density that produces the most OTA in a series quorum density. Moreover, the GprC that classified as sugar sensor, and intracellular adenylate cyclase (AcyA)-cAMP-PKA pathway that in response to ligands glucose and HODEs are verified. Furthermore, GprC and AcyA regulate the primary metabolism as well as secondary metabolism, and further affects the growth of A. ochraceus during the entire life cycle. These studies highlight a crucial G protein signaling pathway for cell communication that is mediated by carbohydrate and oxylipins, and clarified a comprehensive effect of fungal development, which include the direct gene regulation and indirect substrate or energy supply. Our work revealed more signal molecules that mediated density information and connected effects on important adaptive behaviors of Aspergillus ochraceus, hoping to achieve comprehensive prevention and control of mycotoxin pollution from interrupting cell communication." Authors Jing Gao, Huiqing Liu, Yuxin Jin, Yunbo Luo, Kunlun Huang, Zhihong Liang Tags Cell communication , G protein-coupled receptor , Mycotoxin , Oxylipin , Second messenger Source Contribute to the GPCR News Coming soon Become a Contributor Classified GPCR News Call for GPCR papers GPCR Industry News Adhesion GPCRs GPCR Events, Meetings, and Webinars Reviews, GPCRs, and more GPCR Binders, Drugs, and more Methods & Updates in GPCR Research GPCRs in Neuroscience GPCRs in Cardiology, Endocrinology, and Taste GPCRs in Oncology and Immunology Structural and molecular insights into GPCR function GPCR Activation and Signaling More from Dr. GPCR Create an account and get our contributors articles in your inbox Subscribe to the Dr. GPCR Monthly Newsletter today! Follow the Dr. GPCR News and get weekly notifications about the GPCR field Share < Previous Next >

Full Agenda Adhesion GPCR workshop 2024 CINVESTAV, Mexico City, Mexico October 23-25 Download PDF Program HERE < Back to Full Agenda Coffee Break with lights snacks Complimentary < Previous Session Next Session >

Dr. GPCR Podcast << Back to podcast list Dr. Lauren M. Slosky About Dr. Lauren M. Slosky Lauren Slosky is an Assistant Professor in the Department of Pharmacology and a member of the Medical Discovery Team on Addiction, a multidisciplinary initiative within the University of Minnesota’s Medical School to advance research and treatment in the field of drug addiction. Dr. Slosky’s research is focused on understanding how neuropeptide G protein-coupled receptors (GPCRs) regulate motivated behavior and how these receptors can be targeted for therapeutic benefit. Dr. Slosky was awarded a B.S. with honors in Molecular and Cellular Biology and Psychology from The University of Arizona in 2011. She received a Ph.D. in Medical Pharmacology from The University of Arizona in 2015 and completed a postdoctoral fellowship in the laboratory of Dr. Marc G. Caron at Duke University. Dr. Slosky opened her laboratory at the University of Minnesota Medical School in 2021. While a postdoctoral fellow, Dr. Slosky characterized a new class of β-arrestin biased allosteric modulators (BAMs) for the neurotensin receptor 1. These ligands stimulate receptor β-arrestin recruitment without activating canonical G protein signaling. Critically, these ligands reduce addiction-associated behaviors in animal models without the side effects characteristic of balanced receptor activation. Because BAMs engage less well-conserved allosteric sites and exert pathway-specific effects on receptor signaling, they are exciting tools for linking distinct signaling pathways with their physiological effects and may serve as the basis for more selective therapeutics. This work was made possible by the optimization of longitudinal intravenous self-administration paradigms for genetically modified mice. Integrating GPCR biology, behavioral pharmacology, and systems neuroscience approaches, the Slosky Lab is now working to understand how the principles of receptor allosterism and functional selectivity can be leveraged in the development of safe and effective treatments for stimulant and opioid use disorders. Dr. Slosky’s work has been recognized through several travel and research awards, including the William James Psychology Award, the Hank Yamamura Endowed Fellowship in Pharmacology, an NIH F32 Postdoctoral Fellowship, and an NIH K99/R00 Pathway to Independence Award. In addition to research, Dr. Slosky is passionate about training the next generation of scientists and increasing diversity, equity, and inclusion in science. An advocate for trainees at all levels, she served as Service Chairperson and Interim President of the Duke University Postdoctoral Association. She is currently a faculty trainer for the University of Minnesota's MS and Ph.D. programs in Pharmacology, Graduate Program in Neuroscience, and Life Sciences Summer Undergraduate Research Program and is working to build relationships with key stakeholders through institutional and community service. Dr. Lauren M. Slosky on the web Twitter University of Minnesota Department Page LinkedIn Google Scholar PubMed Research Gate Dr. GPCR Ecosystem Thanks for listening to this podcast episode This short survey will help us understand your needs to bring you exciting and informative content; this short survey should take 5 minutes to fill. Listen and subscribe to where you get your podcasts. << Previous Podcast Episode Next Podcast Episode >>

Dr. GPCR Podcast << Back to podcast list Dr. Paul J. Gasser About Dr. Paul J. Gasser " I received my BS and MS in Zoology & Physiology at the University of Wyoming, where I studied signaling processes involved in light-induced regulation of melatonin synthesis in the rainbow trout pineal organ, a directly photosensitive endocrine organ. I received my PhD in Biology at Arizona State University, where I worked in the lab of Miles Orchinik, studying cellular mechanisms underlying non-genomic actions of corticosteroid hormones. My postdoctoral work, conducted at the University of Bristol, UK, in Christopher Lowry's lab, examined the role of organic cation transporter 3 (OCT3) in the regulation of monoamine signaling in the brain. I joined the faculty of Biomedical Sciences at Marquette in 2007. I teach undergraduate Biochemistry and a variety of graduate neuroscience courses. Research in my lab is currently focused on understanding the signal transduction pathways activated by beta-adrenergic receptors localized to the inner nuclear membrane and their role in the regulation of gene expression." Dr. Paul J. Gasser on the web Gasser Lab Marquette University Google Scholar ResearchGate LinkedIn Twitter Dr. GPCR Thanks for listening to this podcast episode This short survey will help us understand your needs to bring you exciting and informative content; this short survey should take 5 minutes to fill. Listen and subscribe to where you get your podcasts. << 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 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 >

Dr. GPCR Podcast << Back to podcast list Dr. GPCR Board About Dr. Yamina Berchiche "Dr. Yamina A. Berchiche is the founder of Dr. GPCR, an ecosystem designed to bring together stakeholders interested in using G-Protein Coupled Receptors (GPCRs) that control virtually everything in the body as drug targets. The mission of Dr. GPCR is to accelerate GPCR drug discovery by sharing the latest research and technology advances in the field and providing exposure to scientists through the Dr. GPCR podcast. Dr. Berchiche obtained her Master’s and Ph.D. in Biochemistry at the University of Montreal in Canada before training at Rockefeller University in New York and the National Institutes of Health in Bethesda, Maryland. She developed expertise over the past two decades studying structure/function relationships of GPCRs using live-cell bioluminescence resonance energy transfer (BRET). Her work focused on chemokine receptors, members of the GPCR family that control cell movement in the body." Dr. Yamina Berchiche on the web Website LinkedIn Facebook Twitter ResearchGate PubMed Google Scholar Dr. GPCR About Dr. Maria Waldhoer "I am a pharmacologist with a ~30 years background in academia and industry, working both in big pharma and biotech settings. My experience in basic research at several universities worldwide and early R&D at Novo Nordisk A/S allowed me to shape a swiss start-up company from a scientifc idea to a thriving Biotech focusing on Systems Biology & AI to accelerate the quest for novel & safer drugs on GPCRs. After a well needed break from the grind, I am now a scientific/business consultant for clients both in Academia and in the Life sciences and Healthcare industry. I am a recent convert and strong advocate for integrating mindfulness and mental wellbeing into demanding work routines." Dr. Maria Waldhoer on the web LinkedIn T witter Pubmed Dr. GPCR About Dr. JoAnn Trejo "Dr. JoAnn Trejo earned her Ph.D. at UC San Diego. She completed her postdoctoral fellowship at UC San Francisco under the guidance of Professor Shaun Coughlin where she worked on the newly discovered protease-activated GPCRs. Dr. Trejo joined the faculty in the Department of Pharmacology at the University of North Carolina in 2000 and then moved to UC San Diego School Medicine, Department of Pharmacology in 2008, where she quickly rose through the ranks to tenured professor in 2012. In 2014, she was appointed Vice-Chair of the Department of Pharmacology. The long-term goal of Dr. Trejo’s research program is to gain a thorough and mechanistic understanding of processes that control cell signaling by protease-activated receptors (PARs) and the impact on vascular inflammation and cancer progression. PARs are GPCRs that are activated through an atypical irreversible proteolytic mechanism. The precise control of PAR signaling is critical for proper temporal and spatial dynamics of signaling and appropriate cellular responses. Discovering new aspects of PAR signaling is important for increasing the fundamental knowledge of GPCR biology and for the identification of drug targets and future drug development. Dr. Trejo’s research has focused on PAR1, which has important functions in hemostasis, thrombosis, inflammation, and cancer and is an important drug target. She has made numerous important discoveries related to the mechanisms that control PAR1 signaling and closely related family members and published extensively on this topic. Dr. Trejo has been continuously funded by the NIH for >20 years and was a recipient of the prestigious American Heart Association Established Investigator Award. Her laboratory is the recognized expert on protease-activated receptors, particularly PAR1, and over the years she has discovered novel aspects of GPCR biology, acquired critical expertise, and rigorous approaches to examine PAR1 function using human cultured cells and mouse models. Dr. Trejo has presented her studies at 52 national/international meetings and 66 academic seminars across the U.S." Dr. JoAnn Trejo on the web UC San Diego Trejo Lab Wikipedia ​​​​LinkedIn Google Scholar Orcid Twitter UC San Diego School of Medicine Researchgate Dr. GPCR About Anne Marie Quinn "Anne Marie Quinn has a long and varied work experience in the biocomputing and bioinformatics fields. From 1987 to 1994, they were the Director of Biocomputing at The Salk Institute, where they managed institute-wide network and biocomputing services, served on the Steering Committee of the San Diego Supercomputer Center, and provided consultation for genetic sequence analysis, molecular modeling and database searching. In 1994, they became a Bioinformatics Scientist at CuraGen Corporation. From 1995 to 2002, they worked at Yale University School of Medicine as the Bioinformatics Core Facility Manager, where they managed a technical support team providing scientific data analysis and database development services, contributed analytic support resulting in authorship of numerous scientific publications and new funding, and developed and co-taught a new course in bioinformatics for graduate students. From 2002 to 2006, they were a Senior Application Scientist at Accelrys, where they were the technical point of contact for customers assessing features of software products for drug discovery and genomic analysis, delivered technical presentations and software demonstrations to prospective customers worldwide, and developed web-based case notes, marketing seminars and product literature for scientific software. Finally, since 2006, they have been the Chief Executive Officer at Montana Molecular, LLC. Anne Marie Quinn attended Yale University from 1998 to 2000, where they earned a Master of Public Health (MPH) degree in Biostatistics and Bioinformatics. Prior to that, they obtained a Bachelor of Arts (B.A.) degree from California State University, Long Beach in 1982." Anne Marie Quinn on the web Google Scholar The Org LinkedIn Twitter Dr. GPCR Thanks for listening to this podcast episode This short survey will help us understand your needs to bring you exciting and informative content; this short survey should take 5 minutes to fill. Listen and subscribe to where you get your podcasts. << Previous Podcast Episode Next Podcast Episode >>

< GPCR News < GPCRs in Oncology and Immunology High Metabolite Concentrations in Portal Venous Blood as a Possible Mechanism for Microbiota Effects on the Immune System, and Western Diseases Published date November 20, 2023 Abstract "We show that the gut bacterial metabolites, short chain fatty acids (SCFAs), are present at exceptionally high concentrations in the portal venous circulation, particularly small blood vessels that emanate from colonic mucosa. Likely, many other metabolites will be present at high concentrations. Herein we propose a model for immune conditioning, whereby metabolites such as butyrate affect immune cells as they pass through the portal venous system. Deficiency of SCFA would lead to pro-inflammatory immune cell skewing through insufficient G-protein coupled receptor (GPCR) signalling, or lack of histone deacetylase (HDAC) inhibition. Such pro-inflammatory immune cells may travel to tissues such as the brain, the lung, the kidney etc and promote disease. This model helps explain how the gut microbiome may be affecting peripheral immune cells, and consequently Western lifestyle diseases, most of which are immune based, in tissues remote from the gut." Authors Quanbo Wang , Charles R Mackay Tags Gut microbiota , Western lifestyle diseases , portal vein , short chain fatty acids Source Contribute to the GPCR News Coming soon Become a Contributor Classified GPCR News Call for GPCR papers GPCR Industry News Adhesion GPCRs GPCR Events, Meetings, and Webinars Reviews, GPCRs, and more GPCR Binders, Drugs, and more Methods & Updates in GPCR Research GPCRs in Neuroscience GPCRs in Cardiology, Endocrinology, and Taste GPCRs in Oncology and Immunology Structural and molecular insights into GPCR function GPCR Activation and Signaling More from Dr. GPCR Create an account and get our contributors articles in your inbox Subscribe to the Dr. GPCR Monthly Newsletter today! Follow the Dr. GPCR News and get weekly notifications about the GPCR field Share < Previous Next >

< GPCR News < GPCRs in Oncology and Immunology Expression prevalence and dynamics of GPCR somatostatin receptors 2 and 3 as cancer biomarkers beyond NET: a paired immunohistochemistry approach Published date November 27, 2023 Abstract "Somatostatin receptors are clinically validated GPCR biomarkers for diagnosis and treatment of various neuroendocrine tumors (NET). Among the five somatostatin receptors, SST2 and SST3 are associated with apoptosis and cell cycle arrest, making these receptor subtypes better differentiated targets in precision oncology. In this study we performed immunohistochemistry of paired tissue microarrays containing 1125 cores, representing 43 tumor types, each stained for SST2 and SST3. A 12-point immunoreactive scoring (IRS) range was used for interpretation of the staining results. We analyzed the results twice, using the conventional positivity IRS cutoffs ≥ 3 and more stringent ≥ 6. Evaluation of receptors expression dynamics was performed for tumor-nodes-metastases (TNM) defined subgroups (ovarian and hepatocellular adenocarcinomas) as a function of their tumor stage. Our results indicate that two-thirds of tested cores exhibit clinically significant expression of at least SST2 or SST3 (IRS ≥ 6). The expression prevalence of both receptors tends to decline with tumor progression. However, an unexpected upregulation of both SST2 and SST3 reemerged in metastases suggesting conserved receptors genetic potential during tumor life cycle. We suggest that SST2 and SST3 should be further explored as potential biomarkers and therapeutic tools for maximizing the efficiency of somatostatin-based precision oncology of solid tumors beyond NET." Authors Mor Oron-Herman , David Kirmayer , Amelie Lupp , Stefan Schulz , Genady Kostenich , Michel Afargan Source Contribute to the GPCR News Coming soon Become a Contributor Classified GPCR News Call for GPCR papers GPCR Industry News Adhesion GPCRs GPCR Events, Meetings, and Webinars Reviews, GPCRs, and more GPCR Binders, Drugs, and more Methods & Updates in GPCR Research GPCRs in Neuroscience GPCRs in Cardiology, Endocrinology, and Taste GPCRs in Oncology and Immunology Structural and molecular insights into GPCR function GPCR Activation and Signaling More from Dr. GPCR Create an account and get our contributors articles in your inbox Subscribe to the Dr. GPCR Monthly Newsletter today! Follow the Dr. GPCR News and get weekly notifications about the GPCR field Share < Previous Next >

Dr. GPCR Podcast << Back to podcast list Dr. Paul Insel About this episode Dr. Paul Insel is currently a Distinguished Professor of Pharmacology and the University of California San Diego. Paul thinks broadly about science and has been actively publishing papers about his ideas on how COVID symptoms could be treated while we wait for a vaccine, particularly about ACE2 and angiotensin. For the past 30 years, he has been the Director of MD/Ph.D. training program at UCSD and has served as Editor or Senior Editor of numerous scientific journals, including but not limited to the Journal of Clinical Investigation, Molecular Pharmacology, British Journal of Pharmacology, and American Journal of Physiology-Cell Physiology. Dr. Paul Insel on the web Insel Laboratory Institute of Engineering in Medicine UC San Diego UCSD Profiles Google PubMed Dr. GPCR Ecosystem Thanks for listening to this podcast episode This short survey will help us understand your needs to bring you exciting and informative content; this short survey should take 5 minutes to fill. Listen and subscribe to where you get your podcasts. << Previous Podcast Episode Next Podcast Episode >>

< GPCR News < GPCRs in Oncology and Immunology Orphan receptor GPR50 attenuates inflammation and insulin signaling in 3T3-L1 preadipocytes Published date November 1, 2022 Abstract Type 2 diabetes (T2DM) is characterized by insulin secretion deficiencies and systemic insulin resistance (IR) in adipose tissue, skeletal muscle, and the liver. Although the mechanism of T2DM is not yet fully known, inflammation and insulin resistance play a central role in the pathogenesis of T2DM. G protein-coupled receptors (GPCRs) are involved in endocrine and metabolic processes as well as many other physiological processes. GPR50 (G protein-coupled receptor 50) is an orphan GPCR that shares the highest sequence homology with melatonin receptors. The aim of this study was to investigate the effect of GPR50 on inflammation and insulin resistance in 3T3-L1 preadipocytes. GPR50 expression was observed to be significantly increased in the adipose tissue of obese T2DM mice, while GPR50 deficiency increased inflammation in 3T3-L1 cells and induced the phosphorylation of AKT and insulin receptor substrate (IRS) 1. Furthermore, GPR50 knockout in the 3T3-L1 cell line suppressed PPAR-γ expression. These data suggest that GPR50 can attenuate inflammatory levels and regulate insulin signaling in adipocytes. Furthermore, the effects are mediated through the regulation of the IRS1/AKT signaling pathway and PPAR-γ expression. Authors Zhenyu Yao, Jun Meng, Jing Long, Long Li, Weicong Qiu, Cairong Li, Jian V Zhang, Pei-Gen Ren Tags Diabetes mellitus type 2; GPR50; IRS1; Insulin signaling; PPAR-γ. Source Contribute to the GPCR News Coming soon Become a Contributor Classified GPCR News Call for GPCR papers GPCR Industry News Adhesion GPCRs GPCR Events, Meetings, and Webinars Reviews, GPCRs, and more GPCR Binders, Drugs, and more Methods & Updates in GPCR Research GPCRs in Neuroscience GPCRs in Cardiology, Endocrinology, and Taste GPCRs in Oncology and Immunology Structural and molecular insights into GPCR function GPCR Activation and Signaling More from Dr. GPCR Create an account and get our contributors articles in your inbox Subscribe to the Dr. GPCR Monthly Newsletter today! Follow the Dr. GPCR News and get weekly notifications about the GPCR field Share < Previous Next >

< GPCR News < GPCRs in Oncology and Immunology A2aR on lung adenocarcinoma cells: A novel target for cancer therapy via recruiting and regulating tumor-associated macrophages Published date May 28, 2023 Abstract "Adenosine 2a receptor (A2aR), a typical GPCR with a high affinity for adenosine, is widely expressed on immune cells, inhibiting anti-tumor immune response accordingly. Here, we identify that A2aR is specifically expressed on tumor cells from lung adenocarcinoma (LUAD) patients, closely related to their prognosis and positively correlated with tumor-associated macrophages (TAMs) infiltration. We hypothesize that blocking A2aR on LUAD cells will inhibit the role of TAMs and control tumor growth. Constructing models of TAMs and LUAD mice, we find that A2aR highly expressed on LUAD cells promotes the secretion of chemokines and polarizing factors through activating PI3K/AKT/NF-κB pathway, thereby promoting the migration and invasion of TAMs. Functionally, blocking A2aR significantly suppresses TAMs infiltration and attenuates tumor burden in LUAD mice. Notably, the M2 polarization of TAMs can also be prevented by inhibiting A2aR in vitro. Together, our studies demonstrate that A2aR on LUAD cells drives TAMs migration and polarization, and blockade of A2aR may support a novel and potent therapeutic option for LUAD." Authors Ying Bai , Xin Zhang , Jiawei Zhou , Jianqiang Guo , Yafeng Liu , Chao Liang , Wenyang Wang , Yingru Xing , Jing Wu , Dong Hu . Tags A2aR , Lung adenocarcinoma , Migration , Polarization , Targeted therapy , Tumor-associated macrophages . Source Contribute to the GPCR News Coming soon Become a Contributor Classified GPCR News Call for GPCR papers GPCR Industry News Adhesion GPCRs GPCR Events, Meetings, and Webinars Reviews, GPCRs, and more GPCR Binders, Drugs, and more Methods & Updates in GPCR Research GPCRs in Neuroscience GPCRs in Cardiology, Endocrinology, and Taste GPCRs in Oncology and Immunology Structural and molecular insights into GPCR function GPCR Activation and Signaling More from Dr. GPCR Create an account and get our contributors articles in your inbox Subscribe to the Dr. GPCR Monthly Newsletter today! Follow the Dr. GPCR News and get weekly notifications about the GPCR field Share < Previous Next >

< GPCR News < GPCRs in Oncology and Immunology The GPCR-Gαs-PKA signaling axis promotes T cell dysfunction and cancer immunotherapy failure Published date June 12, 2023 Abstract "Immune checkpoint blockade (ICB) targeting PD-1 and CTLA-4 has revolutionized cancer treatment. However, many cancers do not respond to ICB, prompting the search for additional strategies to achieve durable responses. G-protein-coupled receptors (GPCRs) are the most intensively studied drug targets but are underexplored in immuno-oncology. Here, we cross-integrated large singe-cell RNA-sequencing datasets from CD8+ T cells covering 19 distinct cancer types and identified an enrichment of Gαs-coupled GPCRs on exhausted CD8+ T cells. These include EP2, EP4, A2AR, β1AR and β2AR, all of which promote T cell dysfunction. We also developed transgenic mice expressing a chemogenetic CD8-restricted Gαs-DREADD to activate CD8-restricted Gαs signaling and show that a Gαs-PKA signaling axis promotes CD8+ T cell dysfunction and immunotherapy failure. These data indicate that Gαs-GPCRs are druggable immune checkpoints that might be targeted to enhance the response to ICB immunotherapies. © 2023. The Author(s), under exclusive licence to Springer Nature America, Inc." Authors Victoria H Wu , Bryan S Yung , Farhoud Faraji , Robert Saddawi-Konefka , Zhiyong Wang , Alexander T Wenzel , Miranda J Song , Meghana S Pagadala , Lauren M Clubb , Joshua Chiou , Sanju Sinha , Marin Matic , Francesco Raimondi , Thomas S Hoang , Rebecca Berdeaux , Dario A A Vignali , Ramiro Iglesias-Bartolome , Hannah Carter , Eytan Ruppin , Jill P Mesirov , J Silvio Gutkind . Source Contribute to the GPCR News Coming soon Become a Contributor Classified GPCR News Call for GPCR papers GPCR Industry News Adhesion GPCRs GPCR Events, Meetings, and Webinars Reviews, GPCRs, and more GPCR Binders, Drugs, and more Methods & Updates in GPCR Research GPCRs in Neuroscience GPCRs in Cardiology, Endocrinology, and Taste GPCRs in Oncology and Immunology Structural and molecular insights into GPCR function GPCR Activation and Signaling More from Dr. GPCR Create an account and get our contributors articles in your inbox Subscribe to the Dr. GPCR Monthly Newsletter today! Follow the Dr. GPCR News and get weekly notifications about the GPCR field Share < Previous Next >

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

Dr. GPCR Podcast << Back to podcast list Dr. Matthew Eddy About Dr. Matthew Eddy Matthew Eddy earned his BA in Chemistry from Oberlin College, where he trained with solid-state NMR expert Professor Manish Mehta . He then earned his Ph.D. in physical chemistry from the Massachusetts Institute of Technology, training under the mentorship of Prof. Robert Griffin . Following this, Dr. Eddy began learning and investigating human GPCRs while training in the laboratories of Professors Raymond Stevens and Kurt Wüthrich at The Scripps Research Institute. Dr. Matthew Eddy on the web Website Dr. GPCR Ecosystem Thanks for listening to this podcast episode This short survey will help us understand your needs to bring you exciting and informative content; this short survey should take 5 minutes to fill. Listen and subscribe to where you get your podcasts. << Previous Podcast Episode Next Podcast Episode >>

< GPCR News < GPCRs in Oncology and Immunology GPR176 promotes fibroblast-to-myofibroblast transition in organ fibrosis progression Published date July 22, 2024 Abstract "Fibrosis is characterized by excessive deposition of extracellular matrix proteins, particularly collagen, caused by myofibroblasts in response to chronic inflammation. Although G protein-coupled receptors (GPCRs) are among the targets of current antifibrotic drugs, no drug has yet been approved to stop fibrosis progression. Herein, we aimed to identify GPCRs with profibrotic effects. In gene expression analysis of mouse lungs with induced fibrosis, eight GPCRs were identified, showing a >2-fold increase in mRNA expression after fibrosis induction. Among them, we focused on Gpr176 owing to its significant correlation with a myofibroblast marker α-smooth muscle actin (αSMA), the profibrotic factor transforming growth factor β1 (TGFβ1), and collagen in a human lung gene expression database. Similar to the lung fibrosis model, increased Gpr176 expression was also observed in other organs affected by fibrosis, including the kidney, liver, and heart, suggesting its role in fibrosis across various organs. Furthermore, fibroblasts abundantly expressed Gpr176 compared to alveolar epithelial cells, endothelial cells, and macrophages in the fibrotic lung. GPR176 expression was unaffected by TGFβ1 stimulation in rat renal fibroblast NRK-49 cells, whereas knockdown of Gpr176 by siRNA reduced TGFβ1-induced expression of αSMA, fibronectin, and collagen as well as Smad2 phosphorylation. This suggested that Gpr176 regulates fibroblast activation. Consequently, Gpr176 acts in a profibrotic manner, and inhibiting its activity could potentially prevent myofibroblast differentiation and improve fibrosis. Developing a GPR176 inverse agonist or allosteric modulator is a promising therapeutic approach for fibrosis." Authors Yasuo Okamoto, Keisuke Kitakaze, Yasuhiro Takenouchi, Rena Matsui, Daisuke Koga, Ryo Miyashima, Hironobu Ishimaru, Kazuhito Tsuboi Tags Fibroblast , Fibrosis , Gpr176 , Myofibroblast , Orphan GPCR , TGFβ1 Source Contribute to the GPCR News Coming soon Become a Contributor Classified GPCR News Call for GPCR papers GPCR Industry News Adhesion GPCRs GPCR Events, Meetings, and Webinars Reviews, GPCRs, and more GPCR Binders, Drugs, and more Methods & Updates in GPCR Research GPCRs in Neuroscience GPCRs in Cardiology, Endocrinology, and Taste GPCRs in Oncology and Immunology Structural and molecular insights into GPCR function GPCR Activation and Signaling More from Dr. GPCR Create an account and get our contributors articles in your inbox Subscribe to the Dr. GPCR Monthly Newsletter today! Follow the Dr. GPCR News and get weekly notifications about the GPCR field Share < Previous Next >

Dr. GPCR Podcast << Back to podcast list Dr. Stephen Ferguson About Dr. Stephen Ferguson Dr. Stephen Ferguson is a Professor in the Department of Cellular and Molecular Medicine at the University of Ottawa. He did B.Sc. in biology at McGill University and received his Ph.D. under the mentorship of Dr. Brian Collier in the Department of Pharmacology and Therapeutics at McGill University (1994). He did his postdoctoral training with Dr. Marc G. Caron at Duke University (1994-1997), where he and his colleagues investigated the role of G protein-coupled receptor kinases and beta-arrestin in regulating G protein-coupled receptor endocytosis, trafficking, and signaling. He has held four Canada Research Chairs since 2001 and was previously a Heart and Stroke Foundation of Canada MacDonald Scholar (1998-2003) and Heart and Stroke Foundation of Ontario Career Investigator (2003-2016). He was a recipient of Canada's Top 40 under 40 award in 2004 and received Queen Elizabeth II, Diamond Jubilee Medal, in 2012. He has also received both Junior (2001) and Senior (2005) investigator awards from the Pharmacological Society of Canada. Most recently, in 2021, he was elected as a Fellow of the Canadian Academy of Health Science (FCAHS). His research career has focused on the investigation of the regulation of G protein-coupled receptors signaling mechanisms in health and disease. He currently holds multiple research grants from the Canadian Institutes of Health Research (CIHR) for his research investigating the role of metabotropic glutamate receptor signaling in Huntington’s and Alzheimer’s disease. Dr. Stephen Ferguson on the web Carlton University Canada Research Chairs Twitter ResearchGate LinkedIn Dr. GPCR Ecosystem Thanks for listening to this podcast episode This short survey will help us understand your needs to bring you exciting and informative content; this short survey should take 5 minutes to fill. Listen and subscribe to where you get your podcasts. << Previous Podcast Episode Next Podcast Episode >>

Dr. GPCR Podcast << Back to podcast list Dr. Antonella Di Pizio About this episode In this episode of the Dr. GPCR podcast , we meet with Dr. Antonella Di Pizio, an independent research group leader at the Leibniz Institute for Food Systems Biology at the Technical University of Munich. Antonella trained as a medicinal chemist in Italy, followed by a Ph.D. in computational medicinal chemistry, during which she developed a taste for structural biology. Antonella then moved to Israel, where she first started working on bitter taste GPCRs in Dr. Masha Niv's lab . Today, Antonella has expanded her research to olfactory GPCRs and trace amine receptors. Join us to learn more about chemosensory GPCRs and how computational pharmacology can help better understand their function. Dr. Antonella Di Pizio on the web Leibniz-Institute for Food Systems Biology at the Technical University of Munich Google Scholar PubMed LinkedIn Dr. GPCR Ecosystem Thanks for listening to this podcast episode This short survey will help us understand your needs to bring you exciting and informative content; this short survey should take 5 minutes to fill. Listen and subscribe to where you get your podcasts. << Previous Podcast Episode Next Podcast Episode >>