Dr. GPCR Podcast << Back to podcast list Dr. GPCR Team 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. Shivani Sachdev Dr. Sachdev is an early career researcher in the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health. Her research centers on developing nanobody-ligand conjugates to target GPCRs, with a focus on receptors relevant for treating osteoporosis, diabetes, and pain. She received her undergraduate degree in Biotechnology from KIIT University in India. She subsequently joined Professor Mark Connor's laboratory at Macquarie University in Australia. Dr. Sachdev pursued Ph.D. in the same lab where she investigated the molecular pharmacology of cannabinoid receptors. She is also very active within the pharmacology community and currently serves on the editorial board of the British Journal of Pharmacology. Given her expertise in GPCR pharmacology and scientific communication, she is poised to make valuable contributions to the field and expand our understanding of GPCR signaling. Dr. Shivani Sachdev on the web NIDDK ReseachGate Google Scholar LinkedIn Twitter Dr. GPCR About Dr. 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. Dr. Inês Pinheiro on the web LinkedIn University of Geneva Twitter Dr. GPCR About Dr. Monserrat Avila Zozaya I did a PhD in cell biology at CINVESTAV, Mexico. During that time, I investigated the effect of lung cancer-related mutations in the GAIN domain of the Latrophilin 3 receptor. My long-term interest is focused on understanding the mechanisms mediated by GPCRs at the cellular communication level. Dr. Monserrat Avila Zozaya on the web LinkedIn Antony Boucard Lab Dr. GPCR About John Azietaku John Teye Azietaku,PhD is a trained pharmacist, holding a Ph.D. in Drug Discovery Biology and Pharmacology from Monash University. Currently serving as a Post Doctoral research fellow at Monash University, John plays a pivotal role in the pharmacological screening of compounds for a commercial drug discovery program. With prior industry experience as a Clinical Research Associate at IQVIA and regulatory officer at the Food and Drug Authority (FDA) in Ghana, John has a proven track record of ensuring compliance with protocols and regulatory standards. Driven by a passion for advancing drug development, John is committed to leveraging his expertise to enhance healthcare outcomes and contribute to the growth of the pharmaceutical and biotech industry. John Azietaku on the web LinkedIn Dr. GPCR About Ya-Tzu Li Ya-Tzu is a Master's student at the University of South Florida, utilizing large-scale virtual drug screening to identify agonists and antagonists targeting Class A GPCRs. Since beginning her undergraduate studies, she has used computational methods like molecular dynamics simulations and free energy landscape analysis to understand the signaling pathways and activation mechanisms of the Dopamine D3 receptor and the CXCR4-CXCL12 complex. In August, Ya-Tzu will continue her academic and research pursuits by beginning her PhD training in Medical Science at USF, aiming to further contribute to the field of medical pharmacology. Ya-Tzu Li on the web LinkedIn Dr. GPCR About Cam Sinh Lu Cam Sinh Lu is a PhD student at Monash Institute of Pharmaceutical Sciences, Monash University, with a deep interest in understanding drug-receptor interactions. With an immense passion for molecular pharmacology, his research focuses on elucidating the molecular basis of membrane protein signalling using quantitative assays and molecular modelling. Further down the track, he aims to apply this knowledge to develop novel chemical treatments for neuronal and cardiovascular diseases. Cam Sinh Lu on the web LinkedIn 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 >>

Retreat 2023 About Program Registration Logo Contest Committee Sponsors GPCR Retreat Program < Back to schedule Cannabinoid compounds to augment L-DOPA treatment in Parkinson's Disease Date & Time Friday, November 3rd / 9:20 AM Abstract Coming Soon About Ali Salahpour "Dr. Salahpour did his undergrad (1993-1996) and PhD (1996-2002) at University of Montreal in the Department of Biochemistry. His PhD work was under the supervision of Dr. Michel Bouvier working on the topic of GPCR dimerization/oligomerization. In November of 2002, he joined the lab of Dr. Marc Caron at Duke University for his post-doctoral training. In the Caron lab, Dr. Salahpour worked on Dopamine Transporter and its role on regulating dopamine transmission and homeostasis. In April 2009, he joined the Department of Pharmacology and Toxicology at University of Toronto and has continued working on dopamine transmission and homeostasis and the role of several of key modulators of the dopamine system, including the dopamine transporter (DAT), the Vesicular Monoamine Transporter 2 (VMAT2), Tyrosine Hydroxylase (TH) and Trace Amine Associate Receptor 1 (TAAR1)." Ali Salahpour on the web University of Toronto Pubmed Google Scholar Twitter Dr. GPCR Previous Event Next Event Great Lakes GPCR Retreat and Club des Récepteurs à Sept Domaines Transmembranaires du Québec Great Lakes GPCR Retreat and Club des Récepteurs à Sept Domaines Transmembranaires du Québec 22nd GPCR Retreat Sponsored by

< GPCR News < GPCRs in Oncology and Immunology GPR4 in the pH-dependent migration of melanoma cells in the tumor microenvironment Published date December 23, 2022 Abstract Due to its high metastatic potential, malignant melanoma is one of the deadliest skin cancers. In melanoma as well as in other cancers, acidification of the tumor microenvironment (= TME, inverse pH-gradient) is a well-known driver of tumor progression and metastasis. Membrane-bound receptors, such as the proton-sensitive GPCR (pH-GPCR) GPR4, are considered as potential initiators of the signaling cascades relevant to malignant transformation. In this study, we investigated the pH-dependent migration of GPR4 wildtype/overexpressing SK-Mel-28 cells by using an impedance-based electrical wounding and migration assay and classical Boyden chamber experiments. Migration of GPR4 overexpressing SK-Mel-28 cells was enhanced in a range of pH 6.5 - pH 7.5 as compared to controls in the impedance-based electrical wounding and migration assay. In Boyden chamber experiments, GPR4 overexpression only increased migration at pH 7.5 in a Matrigel-free setup, but not at pH 6.5. Results indicate that GPR4 is involved in the migration of melanoma cells, especially in the tumor periphery, and that this process is affected by pH in the TME. Authors Judith Anthea Stolwijk , Susanne Wallner , Judith Heider , Bernadett Kurz , Lisa Pütz , Stefanie Michaelis , Barbara Goricnik , Julia Erl , Linda Frank , Mark Berneburg , Frank Haubner , Joachim Wegener , Stephan Schreml Tags Boyden chamber , ECIS , GPR4 , impedance , malignant melanoma , migration , pH-GPCR. 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 Episodes 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 where you get your podcasts

Dr. GPCR Podcast << Back to podcast list Dr. Shivani Sachdev About Dr. Shivani Sachdev "Dr. Sachdev is an early career researcher in the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health. Her research centers on developing nanobody-ligand conjugates to target GPCRs, with a focus on receptors relevant for treating osteoporosis, diabetes, and pain. She received her undergraduate degree in Biotechnology from KIIT University in India. She subsequently joined Professor Mark Connor's laboratory at Macquarie University in Australia. Dr. Sachdev pursued Ph.D. in the same lab where she investigated the molecular pharmacology of cannabinoid receptors. She is also very active within the pharmacology community and currently serves on the editorial board of the British Journal of Pharmacology. Given her expertise in GPCR pharmacology and scientific communication, she is poised to make valuable contributions to the field and expand our understanding of GPCR signaling." Dr. Shivani Sachdev on the web NIDDK ReseachGate Google Scholar LinkedIn Twitter Dr. GPCR 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 Insel About this episode In 1975, Dr. Paul Insel was at the FASEB experimental biology meeting in Atlantic City. During dinner with colleagues and Alfred Gillman , co-recipient of the 1994 Nobel Prize in Physiology or Medicine for their discovery of G-proteins and their role in signal transduction in cells, Paul was designated to go to Gillman’s lab . That summer, he used radioligand binding methods to dissect receptor function from the adenylyl cyclase activated by ligands, including adrenaline. From that point on, Paul was hooked and has since studied receptor function in human physiology, receptor molecular pharmacology in cells, and animal models, and as he puts it has now he’s "gone full circle" back to studying GPCRs important in human pathophysiology. Today, Paul and his team focus on previously unrecognized receptors with the hopes to use these as novel drug targets. 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 Exploiting frequent and specific expression of PRL3 in pediatric solid tumors for first-in-child use of PRL3-zumab humanized antibody Published date September 21, 2023 Abstract "Phosphatase of regenerating liver 3 (PRL3) is a specific tumor antigen overexpressed in a broad range of adult cancer types. However, its physiological expression in pediatric embryonal and mesenchymal tumors and its association with clinical outcomes in children is unknown. We sought to profile the expression of PRL3 in pediatric tumors in relation to survival outcomes, expression of angiogenesis markers, and G-protein-coupled receptor (GPCR)-mitogen-activated protein kinase (MAPK) signaling targets. PRL3-zumab, a first-in-class humanized antibody, was administered in a dose escalation schedule in a first-in-child clinical trial to study toxicity, pharmacokinetics, and clinical outcomes. Among 64 pediatric tumors, PRL3 was most frequently expressed in neuroblastoma (100%), rhabdomyosarcoma and non-rhabdomyosarcoma soft tissue sarcomas (71%), and renal sarcomas (60%) but absent in paired normal tissues. PRL3 was expressed in 75% of relapsed tumors and associated with shorter median event-free survival. Microarray profiling of PRL3-positive tumors showed elevation of angiogenin, TIMP1 and TIMP2, and GPCR-MAPK signaling proteins that commonly interacted with PRL3. The first use of PRL3-zumab in a pediatric patient saw no adverse events. A 28.6% reduction in maximum target lesion diameter was achieved when PRL3-zumab was administered concurrently with hypofractionated radiation. These findings support wider exploration of PRL3 expression in embryonal and mesenchymal tumors and further clinical application of PRL3-zumab in pediatric patients." Authors Amos Hong Pheng Loh , Min Thura , Abhishek Gupta , Sheng Hui Tan , Kelvin Kam Yew Kuan , Koon Hwee Ang , Khurshid Merchant , Kenneth Tou En Chang , Hui Yi Yon , Yong Chen , Mathew Hern Wang Cheng , Arjandas Mahadev , Matthew Chau Hsien Ng , Michaela Su-Fern Seng , Prasad Iyer , Pei Ling Chia , Shui Yen Soh , Qi Zeng Tags PRL3 , PTP4A3 , PRL3-zumab , Wilms tumor , neuroblastoma , non-rhabdomyosarcoma soft tissue sarcoma , osteosarcoma , pediatric tumors , rhabdomyosarcoma 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 G protein-coupled receptors: A target for microbial metabolites and a mechanistic link to microbiome-immune-brain interactions Published date October 1, 2023 Abstract "Human-microorganism interactions play a key role in human health. However, the underlying molecular mechanisms remain poorly understood. Small-molecules that offer a functional readout of microbe-microbe-human relationship are of great interest for deeper understanding of the inter-kingdom crosstalk at the molecular level. Recent studies have demonstrated that small-molecules from gut microbiota act as ligands for specific human G protein-coupled receptors (GPCRs) and modulate a range of human physiological functions, offering a mechanistic insight into the microbe-human interaction. To this end, we focused on analysis of bacterial metabolites that are currently recognized to bind to GPCRs and are found to activate the known downstream signaling pathways. We further mapped the distribution of these molecules across the public mass spectrometry-based metabolomics data, to identify the presence of these molecules across body sites and their association with health status. By combining this with RNA-Seq expression and spatial localization of GPCRs from a public human protein atlas database, we inferred the most predominant GPCR-mediated microbial metabolite-human cell interactions regulating gut-immune-brain axis. Furthermore, by evaluating the intestinal absorption properties and blood-brain barrier permeability of the small-molecules we elucidated their molecular interactions with specific human cell receptors, particularly expressed on human intestinal epithelial cells, immune cells and the nervous system that are shown to hold much promise for clinical translational potential. Furthermore, we provide an overview of an open-source resource for simultaneous interrogation of bioactive molecules across the druggable human GPCRome, a useful framework for integration of microbiome and metabolite cataloging with mechanistic studies for an improved understanding of gut microbiota-immune-brain molecular interactions and their potential therapeutic use." Authors Gajender Aleti , Emily A Troyer , Suzi Hong Tags G protein-coupled receptors , Gut microbiota , Human-microbiota interactions , Immune system , Inflammation , Metabolites 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 Comparative Analysis of the GNAI Family Genes in Glioblastoma through Transcriptomics and Single-Cell Technologies Published date October 23, 2023 Abstract Glioblastoma multiforme (GBM) is one of the most aggressive cancers with a low overall survival rate. The treatment of GBM is challenging due to the presence of the blood-brain barrier (BBB), which hinders drug delivery. Invasive procedures alone are not effective at completely removing such tumors. Hence, identifying the crucial pathways and biomarkers for the treatment of GBM is of prime importance. We conducted this study to identify the pathways associated with GBM. We used The Cancer Genome Atlas (TCGA) GBM genomic dataset to identify differentially expressed genes (DEGs). We investigated the prognostic values of the guanine nucleotide-binding protein G(i) alpha subunit (GNAI) family of genes in GBM using a Chinese Glioma Genome Atlas (CGGA) dataset. Within this dataset, we observed the association in the tumor microenvironment between the gene expression of GNAI subunit 3 (GNAI3) and a poor prognosis. MetaCore and gene ontology (GO) analyses were conducted to explore the role of GNAI3 in co-expressed genes and associated signaling pathways using a transcript analysis. Notable pathways included "Cytoskeleton remodeling regulation of actin cytoskeleton organization by the kinase effectors of Rho GTPases" and "Immune response B cell antigen receptor (BCR) pathway". A single-cell analysis was used to assess GNAI3 expression in GBM. The results demonstrated that GNAI family genes, specifically GNAI3, were significantly associated with carcinogenesis and malignancy in GBM patients. Our findings suggest that the GNAI3 gene holds potential as a prognostic biomarker for GBM. Authors Ahmad Raza , Meng-Chi Yen , Gangga Anuraga , Iram Shahzadi , Muhammad Waqar Mazhar , Hoang Dang Khoa Ta , Do Thi Minh Xuan , Sanskriti Dey , Sachin Kumar , Adrian Wangsawijaya Santoso , Bianca Tobias William , Chih-Yang Wang Tags G-protein-coupled receptor (GPCR) , genome , glioblastoma , malignancy , molecular biomarker , prognosis , signaling pathway . 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 Structural Basis for the Recognition of GPRC5D by Talquetamab, a Bispecific Antibody for Multiple Myeloma Published date August 22, 2024 Abstract "Multiple myeloma (MM) is a complex hematological malignancy characterized by abnormal antibody production from plasma cells. Despite advances in the treatment, many patients experience disease relapse or become refractory to treatment. G-protein-coupled receptor class C group 5 member D (GPRC5D), an orphan GPCR predominantly expressed in MM cells, is emerging as a promising target for MM immunotherapy. Talquetamab, a Food and Drug Administration-approved T-cell-directing bispecific antibody developed for treatment of MM, targets GPRC5D. Here, we elucidate the structure of GPRC5D complexed with the Fab fragment of talquetamab, using cryo-electron microscopy, providing the basis for recognition of GPRC5D by the bispecific antibody. GPRC5D forms a symmetric homodimer with the interface between transmembrane helix (TM) 4 of one protomer and TM4/5 of the other protomer. A single talquetamab Fab interacts with the GPRC5D dimer with its orientation toward the dimer interface. All six complementarity-determining regions of talquetamab engage with extracellular loops and TM3/5/7. In particular, the side-chain of an arginine residue from the antibody penetrates into a shallow pocket on the extracellular surface of GPRC5D. The structure offers insights for optimizing antibody design against GPRC5D for relapsed or refractory MM therapy." Authors Jihong Jeong, Junhyeon Park, Geun Young Mo, Jinwoo Shin, Yunje Cho Tags GPRC5D , Multiple myeloma , class C GPCR , cryo-EM structure , talquetamab 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 G protein-coupled receptor-mediated signaling of immunomodulation in tumor progression Published date July 31, 2024 Abstract "G protein-coupled receptors (GPCRs) are essential contributors to tumor growth and metastasis due to their roles in immune cell regulation. Therefore, GPCRs are potential targets for cancer immunotherapy. Here, we discuss the current understanding of the roles of GPCRs and their signaling pathways in tumor progression from an immunocellular perspective. Additionally, we focus on the roles of GPCRs in regulating immune checkpoint proteins involved in immune evasion. Finally, we review the progress of clinical trials of GPCR-targeted drugs for cancer treatment, which may be combined with immunotherapy to improve treatment efficacy. This expanded understanding of the role of GPCRs may shed light on the mechanisms underlying tumor progression and provide a novel perspective on cancer immunotherapy." Authors Guang-Hong Qiu, Bin Yu, Mei Ma Tags GPCRs , cancer immune checkpoints , cancer immunotherapy , immune cells , 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 >

< GPCR News < GPCRs in Oncology and Immunology NPFF stimulates human ovarian cancer cell invasion by upregulating MMP-9 via ERK1/2 signaling Published date September 1, 2023 Abstract "Neuropeptide FF (NPFF) belongs to the RFamide peptide family. NPFF regulates a variety of physiological functions by binding to a G protein-coupled receptor (GPCR), NPFFR2. Epithelial ovarian cancer (EOC) is a leading cause of death among gynecological malignancies. The pathogenesis of EOC can be regulated by many local factors, including neuropeptides, through an autocrine/paracrine manner. However, to date, the expression and/or function of NPFF/NPFFR2 in EOC is undetermined. In this study, we show that the upregulation of NPFFR2 mRNA was associated with poor overall survival in EOC. The TaqMan probe-based RT-qPCR showed that NPFF and NPFFR2 were expressed in three human EOC cells, CaOV3, OVCAR3, and SKOV3. In comparison, NPFF and NPFFR2 expression levels were higher in SKOV3 cells than in CaOV3 or OVCAR3 cells. Treatment of SKOV3 cells with NPFF did not affect cell viability and proliferation but stimulated cell invasion. NPFF treatment upregulates matrix metalloproteinase-9 (MMP-9) expression. Using the siRNA-mediated knockdown approach, we showed that the stimulatory effect of NPFF on MMP-9 expression was mediated by the NPFFR2. Our results also showed that ERK1/2 signaling was activated in SKOV3 cells in response to the NPFF treatment. In addition, blocking the activation of ERK1/2 signaling abolished the NPFF-induced MMP-9 expression and cell invasion. This study provides evidence that NPFF stimulates EOC cell invasion by upregulating MMP-9 expression through the NPFFR2-mediated ERK1/2 signaling pathway." Authors Ze Wu , Qiongqiong Jia , Boqun Liu , Lanlan Fang , Peter C K Leung , Jung-Chien Cheng Tags Invasion , MMP-9 , NPFFR2 , Neuropeptide FF , Ovarian cancer 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. Richard Premont About Dr. Richard Premont "Dr. Premont obtained his B.S. in Biology and Chemistry at the California Institute of Technology in 1985, and M.Ph . and Ph.D. in Biomedical Sciences (Pharmacology) at Mount Sinai School of Medicine (City University of New York) in 1990 and 1992, working with Ravi Iyengar on regulation/desensitization of the liver glucagon receptor and glucagon-stimulated adenylyl cyclase system. In 1992, he won a Helen Hay Whitney Foundation fellowship to support his post-doctoral work with Robert Lefkowitz and Marc Caron at Duke University. His initial project to identify and clone taste receptors was unsuccessful, but led to the identification of GRK5 and continued focus on GRKs (particularly GRKs 4,5,6) and arrestins as GPCR regulators and as mediators of distinct signaling pathways through partners including GIT1. In 1999, obtained an independent faculty position at Duke in Gastroenterology, where he remained until 2018 studying GPCRs and their signaling pathways in the liver and in liver disease. In 2018, he moved to Harrington Discovery Institute and Case Western Reserve University, where he studies GPCR regulation by S-nitrosylation. My research focus is on understanding how distinct cellular signaling pathways interact and are coordinated to produce integrated physiological responses, and how dysregulation of this coordination results in pathophysiology. For this, we have worked in three main areas: the regulation of G protein-coupled receptor signaling particularly by the G protein-coupled receptor kinase (GRK) – beta-arrestin system, the coordination of heterotrimeric G protein, small GTP-binding protein and protein kinase pathways by GIT/PIX scaffolding complexes during cellular signaling, and characterizing the role of protein S-nitrosylation as a signaling post-translational modification in mediating and regulating cellular signaling pathways, particularly in conjunction with better characterized signaling systems. In our work, we utilize methods including structural biology and proteomics, molecular biology and biochemical enzymology, primary and model cell culture, and transgenic, knockout, knock-in and conditional models of mouse physiology and behavior." Dr. Richard Premont on the web Google Scholar LinkedIn 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 >>

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 >>

Dr. GPCR Podcast << Back to podcast list Dr. Bryan Roth About this episode Dr. Bryan Roth is the Michael Hooker Distinguished Professor of Pharmacology at the University of North Carolina Chapel Hill School of Medicine. After receiving his MD and Ph.D. in Biochemistry from St. Louis University in 1983, he subsequently trained in pharmacology (NIH), molecular biology, and psychiatry at Stanford. Bryan leads a $26.9 Million project to create better psychiatric medications, among other things. But, it wasn’t always this way. Bryan got fascinated with receptors after attending the lecture of a visiting professor on neurotransmission while in college in Montana, where he is from. He was determined to work on psychiatric disorders and persevered even when he was told several times he would never make it as a basic scientist and would never publish anything important. Join me and learn more about Bryan and his work. Dr. Bryan Roth on the web UNC School of Medicine / Pharmacology Roth Lab Roth Leads $26.9 Million Project to Create Better Psychiatric Medications LinkedIn Bryan Roth on Twitter Roth Lab on Twitter Google Scholar 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 Dr. Demet Araç About Dr. 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." Dr. Demet Araç on the web University of Chicago Araç Laboratory Google Scholar Twitter Dr. GPCR AI Summary AI-generated content may be inaccurate or misleading. Always check for accuracy. Quick recap Yamina and Demet discussed their personal backgrounds, academic backgrounds, and career paths, with a focus on their experiences in the field of GPCR (G protein-coupled receptor). Demet shared his journey of studying adhesion GPCRs, the challenges he faced, and the progress made in understanding their structure and function. They also discussed the ongoing developments in the GPCR field, the upcoming adhesion GPCR consortium meeting, and the naming conventions of proteins in the field. Lastly, they shared their views on pursuing one's passions and not being afraid of the unknown, and Demet expressed his satisfaction with his first podcast experience. Next steps • Yamina will send an email to Demet, encouraging him to distribute information about the Doctor GPCR Symposium to his team, including students, postdocs, and PhD students, and will share the recording of the podcast with Demet for the same purpose. • Demet will distribute information about the Doctor GPCR Symposium to his team and encourage his students, postdocs, and PhD students to contact Yamina for potential speaking opportunities at the symposium or other events. Summary Personal Backgrounds and GPCR Interest Yamina and Demet had a discussion about their personal backgrounds, interests, and experiences. Yamina shared her experiences of living in different countries and the adaptability skills it required. Demet, who had studied various subjects including chemistry, physics, biology, and math, shared his interest in science and physics. He also opened up about his childhood experiences of living in a place with limited pedestrian infrastructure. Yamina inquired about Demet's interest in studying GPCRs, and he explained his motivation stemmed from his experiences as an international student. They also acknowledged the cultural differences between Demet's home country, Turkey, and Yamina's, Canada. Academic Backgrounds and Career Paths Discussion Demet and Yamina discussed their academic backgrounds and career paths, with a focus on their experiences in academia. Demet shared that his interest in science led him to study biology, genetics, and molecular biophysics in Turkey and the United States, eventually becoming a professor at UT Southwestern Medical Center in Dallas. Yamina asked about Demet's career aspirations, to which he responded that he pursued science because he enjoyed it. They also discussed their scientific journeys, focusing on their work on adhesion GPCRs, a field that was largely neglected at the time. Demet's research on the gain domain of adhesion GPCRs started during his postdoctoral studies and continued into his faculty position, despite initial challenges in securing funding. Demet's Journey in Studying Adhesion GPCRs Demet discussed his journey in studying adhesion GPCRs, outlining his collaborations, challenges, and the progress made in understanding their structure and function. He explained that initially, the field lacked adequate tools, and his lab had to develop new techniques to work with these complex proteins. Over the years, Demet's team expanded their collaborations and improved their understanding of the GPCRs through various approaches, including structural biology and signaling assays. Yamina expressed her appreciation for Demet's work and asked about the development of the GPCR field over time. Demet explained that since the year 2000, the field has seen significant growth, with important discoveries such as the transmembrane region structures mediated by agonists. GPCR Field and Naming Convention Discussion Demet and Yamina discussed the ongoing developments in the GPCR field and the upcoming adhesion GPCR consortium meeting, which Anthony will be organizing in Mexico in October. They also addressed the naming conventions of proteins in the field, with Yamina expressing concern about the potential confusion caused by changes in nomenclature. Lastly, they shared their preferences for GPCRs, with Demet expressing a particular fondness for certain adhesion GPCRs. GPCR Field Progress and Advice for Junior Scientists Demet and Yamina discussed the progress of their research in the GPCR (G protein-coupled receptor) field, specifically focusing on adhesion GPCRs. Demet shared that they have been working on the Latrophilin project since 2013, screening about 20 adhesion GPCRs, with the Latrophilin 3 construct proving most successful. They also discussed the importance of the extracellular region of these receptors and its potential as a drug target. Demet highlighted a series of realizations over the years about the importance of the GPCR field and its applications, emphasizing that it's not just about one "Aha!" moment. Yamina expressed her love for the GPCR field and asked for advice for junior scientists interested in the same. Embracing Passions and Embracing Unknowns Demet and Yamina discussed the importance of pursuing one's passions and not being afraid of the unknown in their chosen fields. Demet shared his belief that he was driven by a biological need to tackle more challenging tasks. Both agreed that one should find work exciting and interesting, as life is too short to spend doing things one doesn't enjoy. Yamina posed the question of what advice Demet would give his younger self, but Demet responded that he wouldn't change his past actions, as he believed they led him to his current fulfilling path. Podcast Experience and Upcoming Collaboration Demet expressed satisfaction about his first podcast experience and showed interest in sharing his insights in future episodes. Yamina shared her plans for an upcoming Doctor GPCR Symposium in June, for which Demet is the first confirmed speaker, and discussed potential challenges and solutions. The conversation ended with an agreement to collaborate in the future, with Yamina expressing her intention to reach out to Demet's students and postdocs for potential podcast participation. 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. 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Retreat 2023 About Program Registration Logo Contest Committee Sponsors GPCR Retreat Program < Back to schedule Interaction with the cell adhesion molecule NEGR1 affects mGluR5 cell signalling Date & Time Friday, November 3rd / 1:30 PM Abstract Coming Soon About Fabiola Ribeiro "Fabiola M. Ribeiro is an Associate Professor at the Universidade Federal de Minas Gerais (UFMG). She obtained her Ph.D. from UFMG in 2006 and, after that, she performed her postdoctorate studies at the University of Western Ontario, London, Canada, under Dr. Stephen Ferguson’s supervision. She returned to Brazil in 2010, when she founded her independent research group. Since then, Dr. Ribeiro has supervised eleven M.Sc. and six Ph.D. students, as well as five post-doctorate fellows. Nowadays, her research group comprises four undergraduates, two M.Sc., and six Ph.D. students, as well as five post-doctorate fellows and a lab technician. Dr. Ribeiro has 86 per reviewed scientific papers published in highly respected scientific journals, including 17 papers published in journals with impact higher than 7. Moreover, Dr. Ribeiro is the first or last author of 33 of these published articles. Dr. Ribeiro H factor is 28, according to Web of Science, and she is an affiliated member of the Brazilian Academy of Science. She was able to have several grants approved in Brazil and abroad, which have granted her research group a laboratory containing all the necessary equipment to perform state-of-the-art technologies. Dr. Ribeiro main scientific contributions include the study of the mechanisms involved in neurodegeneration and the characterization of neuroprotective drugs acting on the glutamatergic system. These drugs were shown to be very effective to rescue the cell death observed in a mouse model of Huntington’s disease (HD), decreasing synaptic loss and enhancing HD related memory impairment." Fabiola Ribeiro on the web Federal University of Minas Gerais, Brazil Pubmed ResearchGate Instagram Dr. GPCR Previous Event Next Event Great Lakes GPCR Retreat and Club des Récepteurs à Sept Domaines Transmembranaires du Québec Great Lakes GPCR Retreat and Club des Récepteurs à Sept Domaines Transmembranaires du Québec 22nd GPCR Retreat Sponsored by

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 >>

< GPCR News < GPCRs in Oncology and Immunology Increased protease-activated receptor 1 autoantibodies are associated with severe COVID-19 Published date December 27, 2022 Abstract In patients with severe #COVID19, increased levels of autoantibodies against PAR1 were found. These might serve as allosteric agonists of PAR1 on endothelial cells and platelets, and thus might contribute to the pathogenesis of microthrombosis in COVID-19. Authors Florian Tran , Danielle M M Harris , Alena Scharmacher , Hanna Graßhoff , Kristina Sterner , Susanne Schinke , Nadja Käding , Jens Y Humrich , Otávio Cabral-Marques , Joana P Bernardes , Neha Mishra , Thomas Bahmer , Jeanette Franzenburg , Bimba F Hoyer , Andreas Glück , Martina Guggeis , Alexander Ossysek , Andre Küller , Derk Frank , Christoph Lange , Jan Rupp , Jan Heyckendorf , Karoline I Gaede , Howard Amital , Philip Rosenstiel , Yehuda Shoenfeld , Gilad Halpert , Avi Z Rosenberg , Kai Schulze-Forster , Harald Heidecke , Gabriela Riemekasten , Stefan Schreiber . 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 GPR56 signaling pathway network and its dynamics in the mesenchymal transition of glioblastoma Published date November 19, 2023 Abstract "G protein-coupled receptor 56 (GPR56/ADGRG1) is a multifunctional adhesion GPCR involved in diverse biological processes ranging from development to cancer. In our earlier study, we reported that GPR56 is expressed heterogeneously in glioblastoma (GBM) and is involved in the mesenchymal transition, making it a promising therapeutic target (Ganesh et al., 2022). Despite its important role in cancer, its mechanism of action or signaling is not completely understood. Thus, based on transcriptomic, proteomic, and phosphoproteomic differential expression data of GPR56 knockdown U373-GBM cells included in our above study along with detailed literature mining of the molecular events plausibly associated with GPR56 activity, we have constructed a signaling pathway map of GPR56 as may be applicable in mesenchymal transition in GBM. The map incorporates more than 100 molecular entities including kinases, receptors, ion channels, and others associated with Wnt, integrin, calcium signaling, growth factors, and inflammation signaling pathways. We also considered intracellular and extracellular factors that may influence the activity of the pathway entities. Here we present a curated signaling map of GPR56 in the context of GBM and discuss the relevance and plausible cross-connectivity across different axes attributable to GPR56 function. GPR56 signaling and mesenchymal transition." Authors Raksha A Ganesh , Krishnan Venkataraman , Ravi Sirdeshmukh Tags GPR56 /ADGRG1 , Mesenchymal transition , Pathway , Signaling , TG2 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 GPR68-ATF4 signaling is a novel prosurvival pathway in glioblastoma activated by acidic extracellular microenvironment Published date January 31, 2024 Abstract " Background: Glioblastoma multiforme (GBM) stands as a formidable challenge in oncology because of its aggressive nature and severely limited treatment options. Despite decades of research, the survival rates for GBM remain effectively stagnant. A defining hallmark of GBM is a highly acidic tumor microenvironment, which is thought to activate pro-tumorigenic pathways. This acidification is the result of altered tumor metabolism favoring aerobic glycolysis, a phenomenon known as the Warburg effect. Low extracellular pH confers radioresistant tumors to glial cells. Notably GPR68, an acid sensing GPCR, is upregulated in radioresistant GBM. Usage of Lorazepam, which has off target agonism of GPR68, is linked to worse clinical outcomes for a variety of cancers. However, the role of tumor microenvironment acidification in GPR68 activation has not been assessed in cancer. Here we interrogate the role of GPR68 specifically in GBM cells using a novel highly specific small molecule inhibitor of GPR68 named Ogremorphin (OGM) to induce the iron mediated cell death pathway: ferroptosis. Method: OGM was identified in a non-biased zebrafish embryonic development screen and validated with Morpholino and CRISPR based approaches. Next, A GPI-anchored pH reporter, pHluorin2, was stably expressed in U87 glioblastoma cells to probe extracellular acidification. Cell survival assays, via nuclei counting and cell titer glo, were used to demonstrate sensitivity to GPR68 inhibition in twelve immortalized and PDX GBM lines. To determine GPR68 inhibition's mechanism of cell death we use DAVID pathway analysis of RNAseq. Our major indication, ferroptosis, was then confirmed by western blotting and qRT-PCR of reporter genes including TFRC. This finding was further validated by transmission electron microscopy and liperfluo staining to assess lipid peroxidation. Lastly, we use siRNA and CRISPRi to demonstrate the critical role of ATF4 suppression via GPR68 for GBM survival. Results: We used a pHLourin2 probe to demonstrate how glioblastoma cells acidify their microenvironment to activate the commonly over expressed acid sensing GPCR, GPR68. Using our small molecule inhibitor OGM and genetic means, we show that blocking GPR68 signaling results in robust cell death in all thirteen glioblastoma cell lines tested, irrespective of genetic and phenotypic heterogeneity, or resistance to the mainstay GBM chemotherapeutic temozolomide. We use U87 and U138 glioblastoma cell lines to show how selective induction of ferroptosis occurs in an ATF4-dependent manner. Importantly, OGM was not-acutely toxic to zebrafish and its inhibitory effects were found to spare non-malignant neural cells. Conclusion: These results indicate GPR68 emerges as a critical sensor for an autocrine pro-tumorigenic signaling cascade triggered by extracellular acidification in glioblastoma cells. In this context, GPR68 suppresses ATF4, inhibition of GPR68 increases expression of ATF4 which leads to ferroptotic cell death. These findings provide a promising therapeutic approach to selectively induce ferroptosis in glioblastoma cells while sparing healthy neural tissue." Authors Charles H Williams , Leif R Neitzel , Jessica Cornell , Samantha Rea , Ian Mills , Maya S Silver , Jovanni D Ahmad , Konstantin G Birukov , Anna Birukova , Henry Brem , Betty Tyler , Eli E Bar , Charles C Hong 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 orphan G protein-coupled receptor 141 expressed in myeloid cells functions as an inflammation suppressor Published date April 29, 2024 Abstract "G protein-coupled receptors (GPCRs) regulate many cellular processes in response to various stimuli, including light, hormones, neurotransmitters, and odorants, some of which play critical roles in innate and adaptive immune responses. However, the physiological functions of many GPCRs and the involvement of them in autoimmune diseases of the central nervous system remain unclear. Here, we demonstrate that GPR141, an orphan GPCR belonging to the class A receptor family, suppresses immune responses. High GPR141 messenger RNA levels were expressed in myeloid-lineage cells, including neutrophils (CD11b + Gr1+), monocytes (CD11b + Gr1-Ly6C+ and CD11b + Gr1-Ly6C-), macrophages (F4/80+), and dendritic cells (CD11c+). Gpr141 -/- mice, which we independently generated, displayed almost no abnormalities in myeloid cell differentiation and compartmentalization in the spleen and bone marrow under steady-state conditions. However, Gpr141 deficiency exacerbated disease conditions of experimental autoimmune encephalomyelitis, an autoimmune disease model for multiple sclerosis, with increased inflammation in the spinal cord. Gpr141 -/- mice showed increased CD11b + Gr1+ neutrophils, CD11b + Gr1- monocytes, CD11c+ dendritic cells, and CD4+ T cell infiltration into the experimental autoimmune encephalomyelitis-induced spinal cord compared with littermate control mice. Lymphocytes enriched from Gpr141 -/- mice immunized with myelin oligodendrocyte glycoprotein 35-55 produced high amounts of interferon-γ, interleukin-17A, and interleukin-6 compared with those from wild-type mice. Moreover, CD11c+ dendritic cells (DCs) purified from Gpr141 -/- mice increased cytokine production of myelin oligodendrocyte glycoprotein 35-55-specific T cells. These findings suggest that GPR141 functions as a negative regulator of immune responses by controlling the functions of monocytes and dendritic cells and that targeting GPR141 may be a possible therapeutic intervention for modulating chronic inflammatory diseases." Authors Atsuya Sawabe, Shogo Okazaki, Akira Nakamura, Ryo Goitsuka, Tomonori Kaifu Tags G protein–coupled receptor 141 , autoimmune disease , dendritic cells , experimental autoimmune encephalomyelitis , monocytes , myeloid cells . 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 CB2 stimulation of adipose resident ILC2s orchestrates immune balance and ameliorates type 2 diabetes mellitus Published date July 3, 2024 Abstract "Development of type 2 diabetes mellitus (T2DM) is associated with low-grade chronic type 2 inflammation and disturbance of glucose homeostasis. Group 2 innate lymphoid cells (ILC2s) play a critical role in maintaining adipose homeostasis via the production of type 2 cytokines. Here, we demonstrate that CB2, a G-protein-coupled receptor (GPCR) and member of the endocannabinoid system, is expressed on both visceral adipose tissue (VAT)-derived murine and human ILC2s. Moreover, we utilize a combination of ex vivo and in vivo approaches to explore the functional and therapeutic impacts of CB2 engagement on VAT ILC2s in a T2DM model. Our results show that CB2 stimulation of ILC2s protects against insulin-resistance onset, ameliorates glucose tolerance, and reverses established insulin resistance. Our mechanistic studies reveal that the therapeutic effects of CB2 are mediated through activation of the AKT, ERK1/2, and CREB pathways on ILC2s. The results reveal that the CB2 agonist can serve as a candidate for the prevention and treatment of T2DM." Authors Pedram Shafiei-Jahani, Shi Yan, Mohammad H Kazemi, Xin Li, Amitis Akbari, Kei Sakano, Yoshihiro Sakano, Benjamin P Hurrell, Omid Akbari Tags CB2 , CP: Immunology , CP: Metabolism , ILC2 , T2DM , adipose inflammation , glucose tolerance , immunotherapy , insulin resistance 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 Minireview: functional roles of tissue kallikrein, kinins, and kallikrein-related peptidases in lung cancer Published date July 3, 2023 Abstract "Despite campaigns and improvements in detection and treatment, lung cancer continues to increase worldwide and represents a major public health problem. One approach to treating patients suffering from lung cancer is to target surface receptors overexpressed on tumor cells, such as GPCR-family kinin receptors, and proteases that control tumor progression, such as kallikrein-related peptidases (KLKs). These proteases have been visualized in recent years due to their contribution to the progression of cancers, such as prostate and ovarian cancer, facilitating the invasive and metastatic capacity of tumor cells in these tissues. In fact, KLK3 is the specific prostate antigen, the only tissue-specific biomarker used to diagnose this malignancy. In lung cancer to date, evidence indicates that KLK5, KLK6, KLK8, KLK11, and KLK14 are the major peptidases regulated and involved in its progression. The expression levels of KLKs in this neoplasm are modulated by the secretome of the different cell types present in the tumor microenvironment, the cancer subtype and the tumor stage, among others. Considering the multiple functions of kinin receptors and KLKs, this review highlights their roles, even considering the SARS-CoV-2 effects. Since lung cancer is often diagnosed in advanced stages, our efforts should focus on early diagnosis, validating for example specific KLKs, especially in high-risk populations such as smokers and people exposed to carcinogenic fumes, oil fields, and contaminated workplaces, unexplored fields to investigate. Furthermore, their modulation could be considered as a promising approach in lung cancer therapeutics." Authors Adriana Stuardo-Parada , Rodrigo López-Muñoz , Franz Villarroel-Espindola , Carlos D Figueroa , Pamela Ehrenfeld Tags KLKs , Kallikrein-related peptidases , Kinin receptors , Kinins , Lung cancer , SARS-CoV-2 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 CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration Published date September 1, 2023 Abstract "Immune responses rely on the rapid and coordinated migration of leukocytes. Whereas it is well established that single-cell migration is often guided by gradients of chemokines and other chemoattractants, it remains poorly understood how these gradients are generated, maintained, and modulated. By combining experimental data with theory on leukocyte chemotaxis guided by the G protein-coupled receptor (GPCR) CCR7, we demonstrate that in addition to its role as the sensory receptor that steers migration, CCR7 also acts as a generator and a modulator of chemotactic gradients. Upon exposure to the CCR7 ligand CCL19, dendritic cells (DCs) effectively internalize the receptor and ligand as part of the canonical GPCR desensitization response. We show that CCR7 internalization also acts as an effective sink for the chemoattractant, dynamically shaping the spatiotemporal distribution of the chemokine. This mechanism drives complex collective migration patterns, enabling DCs to create or sharpen chemotactic gradients. We further show that these self-generated gradients can sustain the long-range guidance of DCs, adapt collective migration patterns to the size and geometry of the environment, and provide a guidance cue for other comigrating cells. Such a dual role of CCR7 as a GPCR that both senses and consumes its ligand can thus provide a novel mode of cellular self-organization." Authors Jonna Alanko , Mehmet Can Uçar , Nikola Canigova , Julian Stopp , Jan Schwarz , Jack Merrin , Edouard Hannezo , Michael Sixt 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. Kevin Pfleger About this episode Dr. Pfleger trained as a pharmacologist and obtained his Ph.D. at the University of Edinburgh. I sat down with Kevin to chat about GPCRs, pharmacology, and his contributions to the field in both the academic and biotech worlds. Professor Pfleger has developed extensive expertise in profiling receptor binding and function at the molecular and cellular levels over the last 20 years, particularly involving GPCRs. He also has globally-recognized expertise in bioluminescence resonance energy transfer (BRET) technology, including his patented Receptor-Heteromer Investigation Technology (Receptor-HIT) for studying heteromers. Kevin is also Director, Biomedical Innovation at The University of Western Australia (UWA) and the MTPConnect Western Australian Life Sciences Innovation Hub. He is Head of Molecular Endocrinology and Pharmacology at the UWA Centre for Medical Research and Harry Perkins Institute of Medical Research, Deputy Director of the Australian Research Council Centre for Personalised Therapeutics Technologies, Chief Scientific Advisor to Dimerix, and co-founder of RAGE Biotech . He currently serves on the Board of the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists and is a member of the British Pharmacological Society International Advisory Group. Join me and learn more about Kevin’s work and how he manages all his responsibilities. Dr. Kevin Pfleger on the web LinkedIn ResearchGate Pubmed Google Scholar University of Western Australia Harry Perkins Institute of Medical Research Dr. GPCR Ecosystem 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. Richard Premont About Dr. Richard Premont "Dr. Premont obtained his B.S. in Biology and Chemistry at the California Institute of Technology in 1985, and M.Ph . and Ph.D. in Biomedical Sciences (Pharmacology) at Mount Sinai School of Medicine (City University of New York) in 1990 and 1992, working with Ravi Iyengar on regulation/desensitization of the liver glucagon receptor and glucagon-stimulated adenylyl cyclase system. In 1992, he won a Helen Hay Whitney Foundation fellowship to support his post-doctoral work with Robert Lefkowitz and Marc Caron at Duke University. His initial project to identify and clone taste receptors was unsuccessful, but led to the identification of GRK5 and continued focus on GRKs (particularly GRKs 4,5,6) and arrestins as GPCR regulators and as mediators of distinct signaling pathways through partners including GIT1. In 1999, obtained an independent faculty position at Duke in Gastroenterology, where he remained until 2018 studying GPCRs and their signaling pathways in the liver and in liver disease. In 2018, he moved to Harrington Discovery Institute and Case Western Reserve University, where he studies GPCR regulation by S-nitrosylation. My research focus is on understanding how distinct cellular signaling pathways interact and are coordinated to produce integrated physiological responses, and how dysregulation of this coordination results in pathophysiology. For this, we have worked in three main areas: the regulation of G protein-coupled receptor signaling particularly by the G protein-coupled receptor kinase (GRK) – beta-arrestin system, the coordination of heterotrimeric G protein, small GTP-binding protein and protein kinase pathways by GIT/PIX scaffolding complexes during cellular signaling, and characterizing the role of protein S-nitrosylation as a signaling post-translational modification in mediating and regulating cellular signaling pathways, particularly in conjunction with better characterized signaling systems. In our work, we utilize methods including structural biology and proteomics, molecular biology and biochemical enzymology, primary and model cell culture, and transgenic, knockout, knock-in and conditional models of mouse physiology and behavior." Dr. Richard Premont on the web Google Scholar LinkedIn 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 >>