Dr. GPCR Podcast << Back to podcast list Dr. Arthur Christopoulos About Dr. Arthur Christopoulos " Arthur Christopoulos is the Professor of Analytical Pharmacology and the Dean of the Faculty of Pharmacy & Pharmaceutical Sciences, Monash University, Australia. His research focuses on novel paradigms of drug action at GPCRs, particularly allosteric modulation and biased agonism, and incorporates computational and mathematical modelling, structural and chemical biology, molecular and cellular pharmacology, medicinal chemistry, and preclinical models of behaviour and disease. His work has been applied to studies encompassing neurological and psychiatric disorders, cardiovascular disease, obesity, diabetes, chronic pain and addiction. He has received substantial, long-term support from international and national competitive, charitable and commercial sources, as well as being academic co-founder of three GPCR-focussed biotechnology companies. Professor Christopoulos has over 360 publications, including in leading international journals such as Nature,Science and Cell, and has delivered over 180 invited presentations. He has served on the Editorial Board of 8 international journals and was a Councillor of the International Union of Basic and Clinical Pharmacology (IUPHAR). He has also been the recipient of multiple awards, including the John J. Abel Award and the Goodman and Gilman Award from the American Society for Pharmacology and Experimental Therapeutics; the Rand Medal from the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists; the British Pharmacological Society’s Gaddum Memorial Award; the IUPHAR Sir James Black Analytical Pharmacology Lecturer; the GSK Award for Research Excellence and a Doctor of Laws (Honoris Causa) from the University of Athens. Since 2014, Clarivate Analytics have annually named him a Highly Cited Researcher in ‘Pharmacology & Toxicology’, and in 2021 also named him a Highly Cited Researcher in the additional category of ‘Biology & Biochemistry’. In 2017, he was elected a Fellow of the Australian Academy of Health and Medical Sciences, in 2018 as a Fellow of the British Pharmacological Society, and in 2021 he was elected a Fellow of the Australian Academy of Science for his seminal contributions to drug discovery. In 2023, he was elected a Fellow of the Pharmaceutical Society of Australia. " Dr. Arthur Christopoulos on the web Monash University Wikipedia Google Scholar LinkedIn Dr. GPCR AI Summary AI-generated content may be inaccurate or misleading. Always check for accuracy. Quick recap Yamina and Arthur from Monash University discussed Arthur's career journey, the importance of hard work, failure, and differentiation in academic and personal lives, and the value of international conferences. They also explored the significance of translating fundamental discoveries into clinical applications, the potential of new drugs, and the unique challenges within universities. Additionally, they discussed the importance of hiring based on differentiation, impact, and interest, the need for workforce development, and the potential of involving junior scientists and postdocs in their podcast. Lastly, they touched upon the global challenges of healthcare workforce growth, climate change, and emerging psychiatric disorders, as well as the importance of recording lectures and making pre-lesson materials available to students. Next steps - Yamina will share notes about PRISM and presentability with Arthur. - Arthur will share the story of PRISM's development and its impact on the field with Yamina. - Yamina will send an invite for a follow-up meeting with Arthur next Saturday at 9 PM. - Arthur and Yamina will prepare for the next meeting, focusing on the concept of biased agonism and discussing Dr. GPCR and the charity status. - Yamina will attempt to book Denise for a future podcast episode. Summary Arthur's Career Journey and Transition to Dean Yamina introduced Arthur to her team and discussed the use of a particular tool for meeting summaries. Arthur shared his career journey from pharmacy to becoming a professor, highlighting the influence of his mentors and the importance of his postdoctoral experience. They discussed the value of hard work, failure, and the significance of differentiation in their personal and academic lives. Towards the end, they focused on Arthur's transition to become Dean and his decision to move from Australia to the United States for a postdoctoral position. Postdoctoral Position, Scientific Dynamics, and New Drug Targets Arthur shared his decision to undertake a postdoctoral position with Nigel Bird's lab in the UK and his experiences of meeting influential figures during his time in the US. He and Yamina discussed the importance of preserving original work, the value of international conferences, and the dynamics between junior and senior scientists in a research environment. They also shared their admiration for the work of a mutual friend and discussed the history of muscarinic receptors, specifically focusing on the role of a compound that Arthur received from Fred. Lastly, they discussed the progress of new drugs targeting specific receptors for various diseases, with Arthur sharing insights on Eli Lilly's compound, Xanomeline, and the potential of M4 PAM for psychosis. Collaborative Research and Translational Approach Arthur and Yamina from Monash University discussed their collaborative approach to scientific research, emphasizing the benefits of combining their complementary skills and interests. They shared their unconventional approaches to research, including the creation of a critical mass of GPCR researchers in Australia and the initiation of a successful series of conferences. They also discussed the relocation of some university labs to facilitate collaboration and overcome the siloed department structure. Additionally, they explored the unique culture and structure of their Institute, highlighting its translational approach to research and its capacity to translate research into therapeutic commercialization. Lastly, Arthur shared three significant moments that shaped his career, including the evolution and impact of analytical pharmacology, particularly highlighting the role of Prism, a data analysis tool. Podcast Format, Team Culture, and Science Yamina and Arthur concluded their discussion and decided to take a short break. They talked about the format and length of their podcast, their professional interests, and their recent successful bid to bring Moderna to their university. They also explored the idea of starting a similar talk show format to 'Between Two Ferns', the importance of maintaining team culture, and the potential health issues among well-known scientists. Lastly, they discussed the growth and development of the Monash Institute of Pharmaceutical Sciences, the importance of knowing when to let go in scientific experiments, and the idea of a panel for building and incubating companies. Arthur's Pandemic Journey and Global Challenges Yamina and Arthur discussed Arthur's experiences during the Covid-19 pandemic, his journey as a research fellow in Australia, and his transition to the role of Dean. Arthur shared his insights into the unique grant funding system in Australia, the importance of impact in research, and the challenges of balancing administrative responsibilities with scientific pursuits. He also reflected on his personal health struggles, the growth of his university, and the faculty's successful response to the Covid crisis. The conversation also touched upon Arthur's career decisions, his scientific achievements, and the importance of learning from mistakes and self-confidence. Lastly, they discussed the global challenges of healthcare workforce growth, climate change, and emerging psychiatric disorders, as well as the importance of recording lectures and having pre-lesson materials available to students. Translating Discovery Into Clinical Application Arthur and Yamina discussed the importance of translating fundamental discoveries into clinical applications in their research, highlighting the unique opportunities presented by their location and partnerships with other institutions. They stressed the necessity of making their research goals clearer, avoiding replication, and adopting a more assertive approach in grant applications. They also emphasized the significance of fundamental discoveries, the role of biotech, and the need for efficiency and process development in university systems. The conversation highlighted ongoing challenges within universities, including resistance to change and the need to communicate expectations and protect established cultures. Hiring Process, Collaboration, and Education-Focused Initiatives Arthur emphasized the importance of differentiation, impact, and interest in their hiring process and fostering a culture of collaboration. He shared his vision of breaking down barriers and promoting education-focused initiatives, encouraging his team to be innovative and apply their skills to education. Yamina expressed a desire to learn from successful leaders and the importance of recognizing talent and matching it with the needs of a particular project. They also discussed the disruption within the pharmaceutical sector, the importance of workforce development, and the need for maintaining a healthy work-life balance. Lastly, they deliberated on involving junior scientists and postdocs in their podcast and the possibility of writing a book about their experiences in academia. 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 Inhibition of Relaxin Autocrine Signaling Confers Therapeutic Vulnerability in Ovarian Cancer Date & Time Friday, November 3rd / 3:55 PM Abstract Coming Soon About Robert Rottapel "Dr. Rottapel is a Senior Scientist at the Princess Margaret Cancer Centre where he holds the Amgen Chair for Cancer Research. He is a Professor in the Departments of Medicine, Immunology and Medical Biophysics at the University of Toronto. After completing his medical studies at George Washington University, the NIH and UCLA, he pursued his postdoctoral studies with Allan Bernstein at the Lunenfeld Research Institute in Toronto and with Patrice Dubreuil at INSERM, France. Dr. Rottapel is a clinical rheumatologist at St. Michael's Hospital, University of Toronto. His clinical expertise is in monogenic autoinflammatory disorders and the autoimmune adverse effect resulting from checkpoint inhibitors in cancer patients. Dr. Rottapel’s research interests lies in the elucidation of signal transduction pathways in cancer, immune and bone cells. He has focussed on developing a comprehensive map of ovarian cancer essential genes using whole genome RNAi and CRISPR technology. This approach has provided insight into novel drivers resulting from the widespread gene copy number aberrations observed in ovarian cancer and the identification of emergent vulnerabilities associated with adaptation pathways required to buffer cancer associated stress states. Several of these targets are being developed for potential new therapeutic strategies in ovarian and pancreatic cancer. A second area of interest has been the elucidation of the molecular basis for a rare autosomal human disease called Cherubism. The adapter protein 3BP2 is mutated in Cherubism. The Rottapel lab has shown that 3BP2 has pleiotrophic function controlling bone homeostasis, immune cell function and scavenger receptor activation." Robert Rottapel on the web The Rottapel Lab Ontario Institute for Cancer Research University of Toronto Pubmed Google Scholar LinkedIn 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 SSTR2 positively associates with EGFR and predicts poor prognosis in nasopharyngeal carcinoma Published date September 27, 2023 Abstract "Aims: Epidermal growth factor receptor (EGFR) belongs to the receptor tyrosine kinases family and overexpression of EGFR has been linked to poor prognosis and cancer progression. Somatostatin receptor 2 (SSTR2) is a G-protein-coupled receptor (GPCR) with diverse biological functions in humans, and it is upregulated through the NF-KB signalling pathway in nasopharyngeal carcinomas (NPC). However, no studies have examined the EGFR and SSTR2 in NPC. This study aimed to investigate whether SSTR2 is associated with EGFR and clinicopathological features in NPC. Methods: Bioinformatics analysis was performed to assess the correlation between EGFR and SSTR2 based on the GEO database. The expression of SSTR2 and EGFR was evaluated by immunohistochemistry (IHC) in 491 cases of NPC and 50 cases of non-cancerous nasopharyngeal epithelium. Results: The bioinformatics analysis and IHC showed a positive correlation between SSTR2 and EGFR in NPC. High expression of SSTR2 and EGFR was significantly increased in NPC patients compared with non-cancerous nasopharyngeal epithelium. High expression of SSTR2 and/or EGFR was associated with a worse outcome and a higher risk of progression. The study found that patients receiving chemoradiotherapy (CR) with high expression of SSTR2, high expression of EGFR, and high coexpression of SSTR2 and EGFR had a poorer prognosis in both progression-free survival (PFS) and overall survival (OS). Interestingly, NPC patients with high expression of SSTR2, high expression of EGFR, high coexpression of EGFR and SSTR2, and EGFR/SSTR2 anyone high expression had a better prognosis with CR combined with targeted therapy. Cox multivariate analysis identified SSTR2 and EGFR as independent poor predictors of PFS. Conclusion: Our study is the first to shed light on the intricate relationship between SSTR2 and EGFR in NPC and provides new insights into the potential benefits of EGFR targeted therapy for patients with high SSTR2 expression. Additionally, SSTR2 has potential as a new biomarker for poor prognosis in NPC patients." Authors Yue Xu , Zihan Quan , Yuting Zhan , Haihua Wang , Jiadi Luo , Weiyuan Wang , Songqing Fan Tags biomarkers , tumor , head and neck neoplasms , immunohistochemistry , proteins 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. Adriano Marchese About Dr. Adriano Marchese Adriano Marchese is a Professor of Biochemistry at the Medical College of Wisconsin. Adriano received his Bachelor of Science degree in Pharmacology in 1991 from the University of Toronto. He continued his graduate studies at the University of Toronto where he earned his MSc (1994) and Ph.D. (1998) in Pharmacology. He then moved to Thomas Jefferson University in Philadelphia, PA, for his postdoctoral training in Jeff Benovic’s laboratory studying the regulation of G protein-coupled receptor trafficking and signaling. In 2004 Adriano joined the faculty of the Department of Pharmacology at Loyola University Chicago. In 2016 he decided to move his lab to the Medical College of Wisconsin in Milwaukee, WI. Adriano’s research has contributed to our understanding of the role that ubiquitin plays in GPCR signaling and trafficking. His laboratory is interested in understanding the mechanisms that govern spatial and temporal regulation of GPCR signaling by -arrestins and post-translational modifications (PTMs), such as phosphorylation, ubiquitination, and SUMOylation. His lab has shown a role for -arrestins and PTMs in GPCR trafficking and signaling and has leveraged this knowledge to reveal the spatial and temporal requirements for GPCR activation of signaling pathways related to cell survival, proliferation, and migration. The ultimate goal of Adriano’s research is to target novel aspects of GPCR signaling for therapeutic development. Dr. Adriano Marchese on the web Twitter LinkedIn Google Scholar 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 Spliceosome mutations are associated with clinical response in a phase 1b/2 study of the PLK1 inhibitor onvansertib in combination with decitabine in relapsed or refractory acute myeloid leukemia Published date November 1, 2023 Abstract "PLK1 is overexpressed in acute myeloid leukemia (AML). A phase 1b trial of the PLK1 inhibitor onvansertib (ONV) combined with decitabine (DAC) demonstrated initial safety and efficacy in patients with relapsed/refractory (R/R) AML. The current study aimed to identify molecular predictors of response to ONV + DAC in R/R AML patients. A total of 44 R/R AML patients were treated with ONV + DAC and considered evaluable for efficacy. Bone marrow (BM) samples were collected at baseline for genomic and transcriptomic analysis (n = 32). A 10-gene expression signature, predictive of response to ONV + DAC, was derived from the leading-edge genes of gene set enrichment analyses (GSEA). The gene signature was evaluated in independent datasets and used to identify associated mutated genes. Twenty percent of the patients achieved complete remission, with or without hematologic count recovery (CR/CRi), and 32% exhibited a ≥50% reduction in bone marrow blasts. Patients who responded to treatment had elevated mitochondrial function and OXPHOS. The gene signature was not associated with response to DAC alone in an independent dataset. By applying the signature to the BeatAML cohort (n = 399), we identified a positive association between predicted ONV + DAC response and mutations in splicing factors (SF). In the phase 1b/2 trial, patients with SF mutations (SRSF2, SF3B1) had a higher CR/CRi rate (50%) compared to those without SF mutations (9%). PLK1 inhibition with ONV in combination with DAC could be a potential therapy in R/R AML patients, particularly those with high OXPHOS gene expression and SF mutations." Authors Peter J P Croucher , Maya Ridinger , Pamela S Becker , Tara L Lin , Sandra L Silberman , Eunice S Wang , Amer M Zeidan Tags AML , Biomarker , Hypomethylating agents , Onvansertib , PLK1 , Splicing 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 Molecular characterization of breast cancer cell pools with normal or reduced ability to respond to progesterone: a study based on RNA-seq Published date August 8, 2023 Abstract "Background: About one-third of patients with estrogen receptor alpha (ERα)-positive breast cancer have tumors which are progesterone receptor (PR) negative. PR is an important prognostic factor in breast cancer. Patients with ERα-positive/PR-negative tumors have shorter disease-free and overall survival than patients with ERα-positive/PR-positive tumors. New evidence has shown that progesterone (P4) has an anti-proliferative effect in ERα-positive breast cancer cells. However, the role of PR in breast cancer is only poorly understood. Methods: We disrupted the PR gene (PGR) in ERα-positive/PR-positive T-47D cells using the CRISPR/Cas9 system. This resulted in cell pools we termed PR-low as P4 mediated effects were inhibited or blocked compared to control T-47D cells. We analyzed the gene expression profiles of PR-low and control T-47D cells in the absence of hormone and upon treatment with P4 alone or P4 together with estradiol (E2). Differentially expressed (DE) genes between experimental groups were characterized based on RNA-seq and Gene Ontology (GO) enrichment analyses. Results: The overall gene expression pattern was very similar between untreated PR-low and untreated control T-47D cells. More than 6000 genes were DE in control T-47D cells upon stimulation with P4 or P4 plus E2. When PR-low pools were subjected to the same hormonal treatment, up- or downregulation was either blocked/absent or consistently lower. We identified more than 3000 genes that were DE between hormone-treated PR-low and control T-47D cells. GO analysis revealed seven significantly enriched biological processes affected by PR and associated with G protein-coupled receptor (GPCR) pathways which have been described to support growth, invasiveness, and metastasis in breast cancer cells. Conclusions: The present study provides new insights into the complex role of PR in ERα-positive/PR-positive breast cancer cells. Many of the genes affected by PR are part of central biological processes of tumorigenesis." Authors Mariana Bustamante Eduardo , Irene Keller , Nathalie Schuster , Stefan Aebi , Rolf Jaggi Tags Breast cancer cell pools , progesterone response , RNA-seq , CRISPR/Cas9 , estrogen receptor alpha , gene expression , Progesterone 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 >

< GPCR News < GPCRs in Oncology and Immunology Metallo-protease Peptidase M84 from Bacillusaltitudinis induces ROS-dependent apoptosis in ovarian cancer cells by targeting PAR-1 Published date June 21, 2024 Abstract "We have purified Peptidase M84 from Bacillus altitudinis in an effort to isolate anticancer proteases from environmental microbial isolates. This metallo-protease had no discernible impact on normal cell survival, but it specifically induced apoptosis in ovarian cancer cells. PAR-1, a GPCR which is reported to be overexpressed in ovarian cancer cells, was identified as a target of Peptidase M84. We observed that Peptidase M84 induced PAR-1 overexpression along with activating its downstream signaling effectors NF-κB and MAPK to promote excessive reactive oxygen species (ROS) generation. This evoked apoptotic death of the ovarian cancer cells through the intrinsic route. In in vivo set-up, weekly intraperitoneal administration of Peptidase M84 in syngeneic mice significantly diminished ascites accumulation, increasing murine survival rates by 60%. Collectively, our findings suggested that Peptidase M84 triggered PAR-1-mediated oxidative stress to act as an apoptosis inducer. This established Peptidase M84 as a drug candidate for receptor mediated targeted-therapy of ovarian cancer." Authors Niraj Nag, Tanusree Ray, Rima Tapader, Animesh Gope, Rajdeep Das, Elizabeth Mahapatra, Saibal Saha, Ananda Pal, Parash Prasad, Amit Pal Tags Cancer , Molecular biology 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 GPR15 expressed in T lymphocytes from RA patients is involved in leukocyte chemotaxis to the synovium Published date November 1, 2022 Abstract The rheumatoid arthritis (RA) inflammatory process occurs in the joints where immune cells are attracted into the synovium to promote remodeling and tissue damage. GPR15 is a G protein-coupled receptor (GPCR) located on chromosome 3 and has similarity in its sequence with chemokine receptors. Recent evidence indicates that GPR15 may be associated with modulation of the chronic inflammatory response. We evaluated the expression of GPR15 and GPR15L in blood and synovial tissue samples from RA patients, as well as to perform a functional migration assay in response to GPR15L. The expression of GPR15 and c10orf99/gpr15l mRNA was analyzed by RT-qPCR. Samples of synovial fluid and peripheral blood were analyzed for CD45+CD3+CD4+GPR15+ and CD45+CD3+CD8+GPR15+ T cell frequency comparing RA patients versus control subjects by flow cytometry. Migration assays were performed using PBMCs isolated from these individuals in response to the synthetic GPR15 ligand. Statistical analysis included Kruskal-Wallis test, T-test, or Mann-Whitney U test, according to data distribution. A higher expression in the mRNA for GPR15 was identified in early RA subjects. The frequencies of CD4+/CD8+ GPR15+ T lymphocytes are higher in RA patients comparing with healthy subjects. Also, the frequency CD4+/CD8+ GPR15+ T lymphocytes are higher in synovial fluid of established RA patients comparing with OA patients. GPR15 and GPR15L are present in the synovial tissue of RA patients and GPR15L promotes migration of PBMCs from RA patients and healthy subjects. Our results suggest that GPR15/GPR15L have a pathogenic role in RA and their antagonizing could be a therapeutic approach in RA. Authors Julio Cesar Fernández-Ruiz, Fátima de Lourdes Ochoa-González, Martín Zapata-Zúñiga, Eduardo Mondragon-Marín, Edgar E Lara-Ramírez, Jose Luis Ruíz-Carrillo, Paola Amayrani DelaCruz-Flores, Esther Layseca-Espinosa, José Antonio Enciso-Moreno, Julio Enrique Castañeda-Delgado. Tags C10ORF99; GPR15; GPR15L; T lymphocytes; chemotaxis; rheumatoid arthritis; synovium. 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 miR-19a may function as a biomarker of oral squamous cell carcinoma (OSCC) by regulating the signaling pathway of miR-19a/GRK6/GPCRs/PKC in a Chinese population Published date September 14, 2023 Abstract "The ability of animals to perceive and respond to sensory information is essential for their survival in diverse environments. While much progress has been made in understanding various sensory modalities, the sense of hygrosensation, which involves the detection and response to humidity, remains poorly understood. In this study, we focused on the hygrosensory, and closely related thermosensory, systems in the vinegar fly Drosophila melanogaster to unravel the molecular profile of the cells of these senses. Using a transcriptomic analysis of over 37,000 nuclei, we identified twelve distinct clusters of cells corresponding to temperature-sensing arista neurons, humidity-sensing sacculus neurons, and support cells relating to these neurons. By examining the expression of known and novel marker genes, we validated the identity of these clusters and characterized their gene expression profiles. We found that each cell type could be characterized by a unique expression profile of ion channels, GPCR signaling molecules, synaptic vesicle cycle proteins, and cell adhesion molecules. Our findings provide valuable insights into the molecular basis of hygro- and thermosensation. Understanding the mechanisms underlying hygro- and thermosensation may shed light on the broader understanding of sensory systems and their adaptation to different environmental conditions in animals." Authors Jijun Chen , Liang Wang , Danhua Ma , He Zhang , Jiayan Fan , Hongyan Gao , Xinyu Xia , Wei Wu , Yuyuan Shi Tags GPCR , GRK6 , OSCC , PKC , miRNA 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. Pierre Eftekhari About Dr. Pierre Eftekhari "Clinical physiologist and biologist , with more than 25 years of experience in drug development. have been engaged in GPCR cellular and clinical pharmacology as scientist or PI in neonatal lupus, Cardiomyopathy, hypertension, chagas disease. I have participated and initiated methodologies for development of pharmacologically active anti-GPCR antibodies like agonist, antagonist, inverse agonist or blocker. During my Scholar period I have published or contributed in 38 published scientific work mainly in the field of immunology and pharmacology of GPCR. The majority of my research is concentrated on rhodopsin family with a few works on metabotropic receptor. Since the creation of Inoviem scientific in Nov. 2011 by myself we have been regularly working with GPCRs for our pharma and biotech clients. The latter mainly in target deconvolution and patient stratification." Dr. Pierre Eftekhari on the web Inoviem Scientific 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 >>

Dr. GPCR Podcast << Back to podcast list Dr. Stephane Angers About Dr. Stephane Angers Dr. Angers is an expert in the field of signal transduction. He obtained his Ph.D. from the Université de Montréal in 2002 under the guidance of Dr. Michel Bouvier . His thesis work led to the development and application of light energy transfer methodology to study protein-protein interaction and signal transduction. From 2002-2006 he was a Howard Hughes Post-Doctoral Fellow at the University of Washington in Seattle under Dr. Randall T. Moon , where he identified and characterized novel components of the Wnt signaling pathway and a new class of E3 ubiquitin ligases . In October 2006, Dr. Angers established his independent research program in the Department of Pharmaceutical Sciences at the Faculty of Pharmacy and the Department of Biochemistry at the University of Toronto. He is the recipient of the Canada Research Chair in Functional Architecture of Signal Transduction. His research program is developed to understand the signaling mechanisms underlying the Wnt and Hedgehog families of growth factors and their signaling mechanisms in development, adult tissue homeostasis, and human diseases. His pioneer work led to the development of novel antibody molecules blocking and activating the Wnt pathway for the treatment of cancers and regenerative medicine applications. He is the scientific founder of two biotech companies, ModMab Therapeutics , and AntlerA Therapeutics , which are pursuing the clinical development of these molecules. ​​​​​​​In September 2021, Dr. Angers was named Director of the Donnelly Centre of Cellular and Biomolecular Research at the University of Toronto, an internationally recognized Research Institute bringing together multidisciplinary teams of scientists. Dr. Stephane Angers on the web Angers Lab The Donnelly Centre Twitter Dr. GPCR Ecosystem LinkedIn 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 Check In Date & Time Thursday, November 2nd / 4:00 PM 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 Dr. Annette Gilchrist About this episode Originally, Annette wanted to be a medical doctor but as luck has it, she didn’t get into medical school when she first applied. Instead, she discovered research and started her Ph.D. the day she should have started medical school. Dr. Gilchrist completed her Ph.D. in Biomedical Sciences / Immunology at the University of Connecticut and went on to become a postdoctoral fellow at UIC (University of Illinois at Chicago). Annette worked in industry, academia and her entrepreneurial side led her to three companies, Cue Biotech , Caden Biosciences , and MyGenomeRx in addition to being a consultant for over a decade. Dr. Gilchrist is also an associate professor at the Department of Pharmaceutical Sciences. Join me and learn more about Annette’s career, our common love for chemokines, and how you can use your training as a scientist in so many different ways. Dr. Annette Gilchrist on the web LinkedIn Midwestern University Google Scholar Pubmed Twitter 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. Nariman Balenga About Dr. Nariman Balenga "I received my Master’s degree from the University of Tehran, Iran, in 2005 by studying the suitability of nanoparticles as porters of DNA vaccination against allergens in mice. Then I pursued my education in the lab of Dr. Maria Waldhoer at the Medical University of Graz, Austria, and received my Ph.D. in Molecular Medicine in 2010 after studying the orphan atypical cannabinoid receptor, GPR55 and its crosstalk with CB1R and CB2R in endothelial cells and neutrophils. I followed my interest in allergy and GPCRs by joining the lab of Dr. Kirk Druey at NIAID/NIH, where I characterized the role of RGS4 and RGS5 in airway hyperresponsiveness and lung fibrosis in acute and chronic mouse models of allergic asthma. I was fascinated by the multitude of processes that are regulated/dysregulated by GPCRs and RGS proteins in the lungs of patients with asthma. At the height of curiosity, a seemingly naïve idea at the dinner table led to a side project by which I characterized the impact of a fungal allergenic source on the function of airway smooth muscle cells. A fungal serine protease allergen with GPCR-modulating features was discovered as a new biomarker and target in patients with severe asthma. In 2015 I joined the University of Maryland School of Medicine as an Assistant Professor. I studied the function of RGS5, calcium-sensing receptor, and an orphan adhesion GPCR, GPR64/ADGRG2 in parathyroid glands of patients with hyperparathyroidism and their impact on body calcium homeostasis and bone resorption in relevant transgenic mice. In 2021, I joined the Ferring Research Institute of Ferring Pharmaceuticals in San Diego as a scientist." Dr. Nariman Balenga on the web Researchgate Linkedin.com 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 A Brief History of allosteric modulation with Dr. Arthur Christopoulos About Dr. Arthur Christopoulos " Arthur Christopoulos is the Professor of Analytical Pharmacology and the Dean of the Faculty of Pharmacy & Pharmaceutical Sciences, Monash University, Australia. His research focuses on novel paradigms of drug action at GPCRs, particularly allosteric modulation and biased agonism, and incorporates computational and mathematical modelling, structural and chemical biology, molecular and cellular pharmacology, medicinal chemistry, and preclinical models of behaviour and disease. His work has been applied to studies encompassing neurological and psychiatric disorders, cardiovascular disease, obesity, diabetes, chronic pain and addiction. He has received substantial, long-term support from international and national competitive, charitable and commercial sources, as well as being academic co-founder of three GPCR-focussed biotechnology companies. Professor Christopoulos has over 360 publications, including in leading international journals such as Nature,Science and Cell, and has delivered over 180 invited presentations. He has served on the Editorial Board of 8 international journals and was a Councillor of the International Union of Basic and Clinical Pharmacology (IUPHAR). He has also been the recipient of multiple awards, including the John J. Abel Award and the Goodman and Gilman Award from the American Society for Pharmacology and Experimental Therapeutics; the Rand Medal from the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists; the British Pharmacological Society’s Gaddum Memorial Award; the IUPHAR Sir James Black Analytical Pharmacology Lecturer; the GSK Award for Research Excellence and a Doctor of Laws (Honoris Causa) from the University of Athens. Since 2014, Clarivate Analytics have annually named him a Highly Cited Researcher in ‘Pharmacology & Toxicology’, and in 2021 also named him a Highly Cited Researcher in the additional category of ‘Biology & Biochemistry’. In 2017, he was elected a Fellow of the Australian Academy of Health and Medical Sciences, in 2018 as a Fellow of the British Pharmacological Society, and in 2021 he was elected a Fellow of the Australian Academy of Science for his seminal contributions to drug discovery. In 2023, he was elected a Fellow of the Pharmaceutical Society of Australia. " Dr. Arthur Christopoulos on the web Monash University Wikipedia Google Scholar LinkedIn Dr. GPCR AI Summary Quick recap Yamina and Arthur discussed Arthur's career journey in pharmacology, including his mentors and significant discoveries related to allosteric receptors. They explored the evolution of the field, allosteric modulation concepts, and potential therapeutic approaches involving autoantibodies and allosteric modulators. Additionally, they covered the importance of target product profiles, reproducibility in experiments, and collaborative efforts such as a potential book on GPCR history. Next steps - Arthur will continue to collaborate with other researchers and drug companies to advance the understanding and application of allosteric modulation. - Arthur will work on designing ligands for specific receptors, aiming to create biased agonists for therapeutic use. Summary Arthur's Career Journey and Allosteric Receptors Yamina and Arthur discussed Arthur's career journey and his contributions to the field of pharmacology, with a focus on allosteric receptors and their modulation. Arthur highlighted his mentors' influence, such as Fred Mitchelson and Nigel Burch, and significant discoveries like the concept of synthetic allosteric modulators by Bruns and Fergus. He also discussed the evolution of the field, from biochemical radioligand binding assays to cell-based functional assays, and the influence of Terry Kenakin and chemical programs on his later work. The conversation ended with Arthur's ongoing research and his development of a new operational model. Yamina emphasized the importance of understanding the historical context of the field and the significance of Arthur's contributions. Allosteric Modulation and Hybrid Molecules Arthur and Yamina discussed the development of an operational model for allosteric modulation, emphasizing the balance between mechanism and empiricism. Arthur shared his career journey, including his collaboration with Patrick Sexton and Jim Burch, and the discovery of hybrid molecules with functional selectivity. They also discussed the re-emergence of interest in certain programs, the importance of connections across receptor families, and the potential of hybrid molecules. Arthur's strategy of consulting drug companies and targeting their posters at conferences was also shared with Yamina. Pharmaceutical Industry Experiences and GPCR History Arthur shared his experiences in the pharmaceutical industry, highlighting the differences between big pharma and biotech. They discussed strategies for analyzing large compound screening data, emphasizing robust assays and addressing issues like shifting curves. Arthur recounted a 2004 visit to a pharma company using replicates in assays. Yamina proposed compiling a book on GPCR history through collaborative interviews, considering a symposium to align terminology. For their upcoming project, Yamina favored a conversational approach, while Arthur suggested a kickoff meeting, with Yamina planning chapters and interviews. Bias Mitigation in Symposium Ideas Arthur and Yamina discussed the concept of bias in the context of the history of the Symposium idea. They reviewed significant early papers related to the topic, including work by Brian Roth, Terry Kenakin, Bill Clarke, and Kelly Burke. They also discussed their own research on chemokine receptors and the importance of understanding the natural environment in drug discovery. Lastly, they touched on a project with Nicola Smith that challenged their previous theories. Allosteric Modulation and Drug Discovery Yamina and Arthur delved into the complexities of protein-protein interactions, specifically allosteric modulation. They discussed various modulatory elements, such as RAMPs, G proteins, and GRKs, with Arthur recounting his initial collaboration with Patrick Sexton on RAMPs and amylin receptors. They also delved into the different signaling of Class B receptors and the potential for modulation at various levels. The discussion underscored the potential of allosteric modulators as drugs, despite challenges in the past due to a lack of understanding about the principles involved. They highlighted the importance of fine-tuning the approach to suit different diseases and interdisciplinary collaboration. The discussion also emphasized the need for a disease-specific approach, considering the clinical context and dialing in the desired effect, as well as the significance of rational drug design principles. Allosteric Modulation and Autoantibodies Discussion Arthur and Yamina discussed the potential of autoantibodies and allosteric modulation in the context of disease and therapeutic approaches. Arthur explained the concept of endogenous allosteric ligands and the possibility of using a neutral allosteric ligand as a preferred therapeutic approach, emphasizing the importance of looking for low level cooperativity factors. They also discussed the potential of certain drugs, like flumazenil, as 'nails' or compounds that could be developed into medicines. The conversation highlighted the importance of establishing the correct disease context, setting up appropriate assays, and understanding the models for their work. They both agreed on the necessity of understanding the target product for an allosteric modulator and working backwards from there. TPP, Allosteric Modulators, and Reproducibility Yamina and Arthur discussed the concept of a target product profile (TPP) in drug development, with Arthur explaining its application in other contexts as well. Yamina appreciated Arthur's expertise and indicated she would be creating an outline for an episode on allosteric modulators. They highlighted the importance of reproducibility in scientific experiments, sharing personal experiences and anecdotes. They also discussed their upcoming trips to the GPCR Colloquium in California and current research in their fields. 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. Benjamin Myers About Dr. Benjamin Myers Ben Myers is an assistant professor at the University of Utah School of Medicine in Salt Lake City, UT, and an investigator with the Huntsman Cancer Institute. Ben’s research focuses on Smoothened and other class F GPCRs which play essential roles in embryonic development and in cancer. His group studies the unusual signaling mechanisms employed by these atypical 7-transmembrane receptors, combining biochemical and structural approaches with cell biology and in vivo models. These studies have revealed new and unexpected ways for membrane lipids to regulate GPCR activity and for GPCRs to control intracellular kinases. More recently, Ben’s lab has begun studying GPCR signaling pathways that operate within the primary cilium, a tiny antenna-shaped structure at the cell surface with critical links to development, physiology, and disease. Ben studied developmental and cancer signaling as a postdoctoral fellow with Philip Beachy at Stanford University. Prior to that, Ben received his Ph.D. from UCSF in 2008, where he worked with David Julius on the structure, function, and physiology of ion channels and GPCRs in the nervous system. Dr. Benjamin Myers on the web Website Twitter Pubmed University of Utah 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 Empowering Drug Discovery for the GPCR Community with Dr. Justin English About Dr. Justin English "Dr. English earned his PhD at UNC Chapel Hill in the laboratory of Dr. Henrik Dohlman and performed his postdoctoral work with Dr. Bryan Roth at the same University. We moved to Salt Lake City, Utah in 2020 to begin his own laboratory in the Department of Biochemistry at the University of Utah School of Medicine. His lab focuses on developing and innovating technologies to solve broad questions in pharmacology, with a specific focus on G-protein coupled receptor signaling and biology." Dr. Justin English on the web The English Lab University of Utah 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 >>

Retreat 2023 About Program Registration Logo Contest Committee Sponsors GPCR Retreat Program < Back to schedule Regulation and role of mitochondria delta opioid receptors Date & Time Friday, November 3rd / 10:40 AM Abstract Coming Soon About Louis Gendron "Dr Louis Gendron, PhD is tenured Professor and Chair of the Department of Pharmacology-Physiology at the Université de Sherbrooke. He has 20+ years of experience in in vitro and in vivo GPCR pharmacology and has published seminal papers where he used various approaches to describe the role of opioid receptors in pain and anagesia as well as to study the mechanisms involved in the cellular trafficking of the delta opioid receptor. Recently, his group reported the first in vivo GPCR interactome, revealing an important number of new potential proteins interacting with GPCRs. Dr Gendron is co-director of the FRQS-funded Quebec Pain Research Network and the Editor-in-Chief in the journal Progress in Neuro-Psychopharmacology & Biological Psychiatry." Louis Gendron on the web Université de Sherbrooke Neurosciences Sherbrooke RQRD Pubmed Google Scholar LinkedIn 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 Small-molecule targeting of GPCR-independent noncanonical G-protein signaling in cancer Published date April 25, 2023 Abstract " Activation of heterotrimeric G-proteins (Gαβγ) by G-protein-coupled receptors (GPCRs) is a quintessential mechanism of cell signaling widely targeted by clinically approved drugs. However, it has become evident that heterotrimeric G-proteins can also be activated via GPCR-independent mechanisms that remain untapped as pharmacological targets. GIV/Girdin has emerged as a prototypical non-GPCR activator of G proteins that promotes cancer metastasis. Here, we introduce IGGi-11, a first-in-class small-molecule inhibitor of noncanonical activation of heterotrimeric G-protein signaling. IGGi-11 binding to G-protein α-subunits (Gαi) specifically disrupted their engagement with GIV/Girdin, thereby blocking noncanonical G-protein signaling in tumor cells and inhibiting proinvasive traits of metastatic cancer cells. In contrast, IGGi-11 did not interfere with canonical G-protein signaling mechanisms triggered by GPCRs. By revealing that small molecules can selectively disable noncanonical mechanisms of G-protein activation dysregulated in disease, these findings warrant the exploration of therapeutic modalities in G-protein signaling that go beyond targeting GPCRs. " Authors Jingyi Zhao , Vincent DiGiacomo , Mariola Ferreras-Gutierrez , Shiva Dastjerdi , Alain Ibáñez de Opakua , Jong-Chan Park , Alex Luebbers , Qingyan Chen , Aaron Beeler , Francisco J Blanco , Mikel Garcia-Marcos . Tags G protein , GPCR , cancer , drug discovery . 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. David E. Gloriam About this episode David Gloriam is a Professor in Computational Receptor Biology at the University of Copenhagen where he leads a research cluster for GPCR function and drug discovery and a Pharmaceutical Data Science unit. His group runs the GPCRdb database where ~4,000 researchers each month retrieve reference data and access online tools for analysis, visualization, and experiment design. David obtained his Ph.D. from Uppsala University in Sweden where he worked on the bioinformatic identification of 24 novel human G protein-coupled receptors. He later identified physiological hormones of such under characterized ‘orphan’ receptors and functional probes for a range of receptors. He completed two postdocs in the UK at the EMBL-European Bioinformatics Institute and GlaxoSmithKline . In 2018 he joined the University of Copenhagen, where he has received an ERC Starting Grant, Lundbeck Foundation Fellowship, and Novo Nordisk Foundation Ascending Investigator awards. Dr. Gloriam is a corresponding member of the Nomenclature Committee of the International Union of Pharmacology (IUPHAR). He is one of the coordinators of recommendations to describe ligand bias towards signaling probes and safer drugs. His group recently developed an online resource of biased ligands and pathway effects to advance the biased signaling field. Join me a learn more about David’s work, his career trajectory, and GPCRdb. Dr. David E. Gloriam on the web LinkedIn ResearchGate Twitter Google Scholar Computation Receptor Biology- Gloriam Group GPCRdb 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. David Sykes About Dr. David Sykes " David Andrew Sykes, BSc Hons Pharmacology, MSc Molecular Biology and Biochemistry, PhD in Molecular Pharmacology & Drug Discovery. David has over 20+ years of experience working in a drug discovery environment mainly in a specialist assay development role and most recently with Novartis. In 2014 David joined the University of Nottingham and began a part-time PhD in Molecular Pharmacology and Drug Discovery that he was awarded in 2020. During this period David has made a significant contribution to the understanding of agonist/ antagonist GPCR kinetic determinants in an area of growing scientific interest. His current interests include the development of HTS fluorescence-based kinetic binding assays specifically designed to assess the kinetics of unlabelled compounds (and chemical fragments) and the use of purified receptor/ effector proteins as tools for drug discovery. " Dr. David Sykes on the web Veprintsev Lab ResearchGate 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 >>

< GPCR News < GPCRs in Oncology and Immunology Chemokine Cxcl1-Cxcl2 heterodimer is a potent neutrophil chemoattractant Published date November 24, 2023 Abstract "Microbial infection is characterized by release of multiple proinflammatory chemokines that direct neutrophils to the insult site. How collective function of these chemokines orchestrates neutrophil recruitment is not known. Here, we characterized the role for heterodimer and show that the Cxcl1-Cxcl2 heterodimer is a potent neutrophil chemoattractant in mice and can recruit more neutrophils than the individual chemokines. Chemokine-mediated neutrophil recruitment is determined by Cxcr2 receptor signaling, Cxcr2 endocytosis, and binding to glycosaminoglycans. We have now determined heterodimer's Cxcr2 activity using cellular assays and Cxcr2 density in blood and recruited neutrophils in heterodimer-treated mice. We have shown that the heterodimer binds glycosaminoglycans with higher affinity and more efficiently than Cxcl1 or Cxcl2. These data collectively indicate that optimal glycosaminoglycan interactions and dampened receptor activity acting in concert in a dynamic fashion promote heterodimer-mediated robust neutrophil recruitment. We propose that this could play a critical role in combating infection." Authors Kirti V Sawant , Krishna Mohan Sepuru , Brigith Penaranda , Emily Lowry , Roberto P Garofalo , Krishna Rajarathnam Tags GPCR , heterodimer , inflammation , leukocyte , proteoglycan 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 Wnt pathway inhibition with the porcupine inhibitor LGK974 decreases trabecular bone but not fibrosis in a murine model with fibrotic bone Published date May 1, 2024 Abstract "G protein-coupled receptors (GPCRs) mediate a wide spectrum of physiological functions, including the development, remodeling, and repair of the skeleton. Fibrous dysplasia (FD) of the bone is characterized by fibrotic, expansile bone lesions caused by activating mutations in GNAS. There are no effective therapies for FD. We previously showed that ColI(2.3)+/Rs1+ mice, in which Gs-GPCR signaling was hyper-activated in osteoblastic cell lineages using an engineered receptor strategy, developed a fibrotic bone phenotype with trabecularization that could be reversed by normalizing Gs-GPCR signaling, suggesting that targeting the Gs-GPCR or components of the downstream signaling pathway could serve as a promising therapeutic strategy for FD. The Wnt signaling pathway has been implicated in the pathogenesis of FD-like bone, but the specific Wnts and which cells produce them remain largely unknown. Single-cell RNA sequencing on long-bone stromal cells of 9-wk-old male ColI(2.3)+/Rs1+ mice and littermate controls showed that fibroblastic stromal cells in ColI(2.3)+/Rs1+ mice were expanded. Multiple Wnt ligands were up- or downregulated in different cellular populations, including in non-osteoblastic cells. Treatment with the porcupine inhibitor LGK974, which blocks Wnt signaling broadly, induced partial resorption of the trabecular bone in the femurs of ColI(2.3)+/Rs1+ mice, but no significant changes in the craniofacial skeleton. Bone fibrosis remained evident after treatment. Notably, LGK974 caused significant bone loss in control mice. These results provide new insights into the role of Wnt and Gs-signaling in fibrosis and bone formation in a mouse model of Gs-GPCR pathway overactivation." Authors Hsuan Lung, Kelly L Wentworth, Tania Moody, Ariane Zamarioli, Apsara Ram, Gauri Ganesh, Misun Kang, Sunita Ho, Edward C Hsiao Tags Wnt pathway inhibition , fibrotic bone disease , fibrous dysplasia (FD) , osteoblasts , trabecular bone , G-protein coupled receptor signaling , GPCR , Gnas , Gsα . 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 Unbiased multitissue transcriptomic analysis reveals complex neuroendocrine regulatory networks mediated by spinal cord injury-induced immunodeficiency Published date September 30, 2023 Abstract "Background: Spinal cord injury (SCI), which causes loss of sensory and motor function in the body below the level of injury, is a devastating disease of the central nervous system. SCI leads to severe secondary immunosuppression, called SCI-induced immunodeficiency syndrome (SCI-IDS), which is characterized by increased susceptibility to infection and further exacerbates neurological dysfunction. Several studies have suggested that SCI-IDS is an independent risk factor for poor neurological prognosis. SCI-IDS predominantly occurs following injury above the T5 levels and eventually leads to systemic immune failure, possibly via the sympathetic-adrenal medullary axis and the hypothalamic‒pituitary‒adrenal (HPA) axis. However, the mechanism remains unclear. Methods and objectives: The concentrations of adrenocorticotropic hormone and cortisol in plasma, as well as changes in sympathetic activity (blood pressure and catecholamine levels in plasma), were assessed in rats in the high-level (T3) spinal cord injury (T3-SCI) group and the low-level (T10) spinal cord injury (T10-SCI) group. Second, the differential regulation of the gene network between the sympathetic-adrenal medullary axis and the HPA axis was explored by histology and multitissue transcriptomics, and the neuroendocrine-immune network associated with SCI-IDS was further elucidated. Results: The spleen and thymus gland, which are secondary immune organs, were significantly atrophied in rats in the T3-SCI group, and the white pulp of the spleen was significantly atrophied. The level of cortisol, which is mediated by the adrenal glands, was markedly elevated, but norepinephrine levels were markedly decreased. There was no difference in adrenocorticotropic hormone expression between any of the groups. The transcriptome analysis results showed that the downregulated differentially expressed genes (DEGs) in the T3-SCI group were enriched in the GO term immunoregulation, indicating that splenic immune function was markedly impaired after high-level SCI. The upregulated DEGs in the hypothalamus (hub genes: Nod2, Serpine1, Cebpb, Nfkbil1, Ripk2, Zfp36, Traf6, Akap8, Gfer, Cxcl10, Tnfaip3, Icam1, Fcgr2b, Ager, Dusp10, and Mapkapk2) were significantly enriched in inflammatory pathways, and the downregulated genes (hub genes: Grm4, Nmu, P2ry12, rt1-bb1, Oprm1, Zfhx2, Gpr83, and Chrm2) were enriched in pathways related to inhibitory Gi-mediated G protein-coupled receptor (Gi-GPCR) neurons and neuropeptide changes. The upregulated genes in the adrenal glands (hub genes: Ciart, per2, per3, cry1, and cry2) were enriched in cortisol secretion and circadian rhythm changes, and the downregulated genes (hub genes: IL7r, rt1-bb, rt1-bb1, rt1-da, rt1-ba, cd74, cxcr3, vcam1, ccl5, bin1, and IL8) were significantly enriched in MHC-mediated immune responses. Conclusions: To explore the possible mechanism underlying SCI-IDS, this study assessed the differential regulation of the gene network associated with neuroendocrine immunity after SCI. Progressive neuroinflammation spreads after injury, and neurotransmission through Gi-mediated G protein-coupled receptors in the HPA axis and neuropeptide production by the hypothalamus are inhibited. Disruption of the connection between the hypothalamus and the adrenal glands causes autonomous regulation of the adrenal glands, disturbance of circadian rhythm and finally hypercortisolemia, leading to general suppression of peripheral adaptive immunity. Neuraxial nerve inflammation caused by SCI persists indefinitely, blocking nerve repair; persistent system-wide immunosuppression in the periphery results in increased susceptibility to infection, leading to poor neurological prognosis." Authors Hong Zeng , Li Cheng , De-Zhi Lu , Shuai Fan , Ke-Xin Wang , Li-Li Xu , Bin Cai , Mou-Wang Zhou , Jin-Wu Wang Tags Hypothalamo-pituitary-adrenal axis , Neuroendocrine immunomodulatory axis , Neuroinflammation , SCI-induced immunodeficiency syndrome , Transcriptome 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. Raul Gainetdinov About Dr. Raul Gainetdinov Raul R. Gainetdinov is the Institute of Translational Biomedicine Director at Saint Petersburg State University (SPBU), Russia. Before SPBU, Raul R. Gainetdinov was a Senior Researcher in the Department of Neuroscience and Brain Technologies at the Italian Institute of Technology in Genova, Italy (2008-2016) and an Associate Research Professor in the Department of Cell Biology at Duke University in North Carolina, USA (1996-2008). From 2013-2018, he was also a Professor at the Skolkovo Institute of Science and Technology (Skoltech), Moscow. Before joining the Department of Cell Biology in 1996 as a postdoc and becoming faculty at Duke in 2000, he researched at the Institute of Pharmacology Russian Academy of Medical Sciences in Moscow (1988-1996). He received a Ph.D. in pharmacology in 1992 from the Russian Academy of Medical Sciences and an M.D. in 1988 from the Second Moscow Medical Institute, Moscow, Russia. Since 2013, he has been elected Chair of the subcommittee for the Dopamine receptors of the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR). As of August 2022, he has over 270 publications in scientific journals (including Science, Nature, Cell, and PNAS) and co-authored 13 patents. His papers were cited over 28,000 times (H-index – 81, ISI Web of Science). In 2018-2020, Raul R. Gainetdinov was included in the Web of Science (WOS) Highly Cited Researchers (HCR) list, representing the top 0.1% of scientists worldwide. Dr. Raul Gainetdinov on the web Saint-Petersburg State University Wikipedia Google Scholar Researchgate Google Dr. GPCR 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 >>