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  • The power of many: Multilevel targeting of representative chemokine and metabolite GPCRs in personalized cancer therapy

    < GPCR News < GPCRs in Oncology and Immunology The power of many: Multilevel targeting of representative chemokine and metabolite GPCRs in personalized cancer therapy Published date September 12, 2024 Abstract "G protein-coupled receptors (GPCRs) are vital cell surface receptors that govern a myriad of physiological functions. Despite their crucial role in regulating antitumor immunity and tumorigenesis, therapeutic applications targeting GPCRs in oncology are currently limited. This review offers a focused examination of selected protumorigenic chemokine and metabolite-sensing GPCRs. Specifically, the review highlights five GPCRs able to orchestrate tumor immunobiology at three main levels: tumor immunity, cancer cell expansion, and blood vessel development. The review culminates by illuminating emerging therapies and discussing innovative strategies to harness the full potential of GPCR-targeted treatments, by applying a multireceptor and patient-specific logic." Authors Donato Inverso, Carlotta Tacconi, Serena Ranucci, Marco De Giovanni Tags Angiogenesis , Cancer , GPCRs , Immunity , Treatment 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 >

  • Distinct sub-cellular signal propagation as a component of functional selectivity

    Retreat 2023 About Program Registration Logo Contest Committee Sponsors GPCR Retreat Program < Back to schedule Distinct sub-cellular signal propagation as a component of functional selectivity Date & Time Saturday, November 4th / 8:15 AM Abstract Coming Soon About Michel Bouvier "Michel Bouvier is a professor of Biochemistry and Molecular Medicine and the CEO of the Institute for Research in Immunology and Cancer ( IRIC ) at the Université de Montréal. Following his Ph.D. in Neurological Sciences at the same university in 1985, he completed a post-doctoral fellow at Duke University in the laboratory of Robert Lefkowitz. In 1989, he returned to Montréal as a professor of biochemistry and a scholar of the Medical Research Council of Canada at the Faculty of Medicine of the Université de Montréal. Since 2001, he holds the Canada Research Chair in Signal Transduction and Molecular Pharmacology. Dr. Bouvier is the author of 300 scientific papers and 15 patents and delivered close to 500 invited conferences. He is a world-renowned expert in the field of cell signaling and GPCRs and made seminal contributions to our understanding of this major class of drug targets. In addition to paradigm shifts including inverse agonism, biased signaling, and pharmacological chaperones, his work on bioluminescence resonance energy transfer (BRET) resulted in the development of screening assays that are now widely used for drug discovery. His work received more than 30,000 citations yielding an h-index of 95. He has supervised the research work of 75 graduate students and 40 post-doctoral fellows. Michel’s scientific contributions were recognized by the attribution of many awards and distinctions including his election as a fellow of the Royal Society of Canada (2014), the Julie Axelrod award from the American Society of Pharmacology and Exerimental Therapeutics (2017), the Wilder Penfield award from the Quebec Government (2017), the innovation award of ADRIQ (2019) and the 2021 Killam prize form the Canada Council for the Arts." Michel Bouvier on the web Wikipedia IRIC Bouvier Lab Google Scholar Pubmed ResearchGate Twitter LinkedIn Universite de Montreal- Department of Biochemistry and Molecular Medicine 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

  • Ep 15 with Dr. Arun Shukla

    Dr. GPCR Podcast << Back to podcast list Dr. Arun Shukla About this episode In this episode of the Dr.GPCR podcast , my guest is Dr. Arun Shukla from the Indian Institute of Technology in Kanpur, India. Arun is currently an Associate Professor & Joy Gill Chair Professor, Intermediate Fellow, Wellcome Trust DBT India Alliance Swarnajayanti Fellow & EMBO Young Investigator at the Department of Biological Sciences and Bioengineering. He earned his master's degree in biotechnology from Jawaharlal Nehru University in India and it was during a biochemistry class where he learned about cell signaling that he became curious and wanted to learn more about it. Arun first started working on GPCRs and their structural characterization at the Max Planck Institute of Biophysics where he completed his doctoral studies in the lab of Dr. Hartmut Michel . Fascinated by GPCRs he wrote to Dr. Bob Lefkowitz and asked him if he could join his lab at Duke University. Dr. Shukla spent several years in the Lefkowitz lab and collaborated extensively with Dr. Brian Kolbika of Stanford University. Join us and learn more about Dr. Shukla’s research and how working in the lab instead of going to classes made him realize that research is what he wants to do for the rest of his life. Dr. Arun Shukla on the web Indian Institute of Technology Dr. Arun Shukla Lab Google Scholar PubMed Wikipedia LinkedIn Twitter 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 >>

  • [Inhibitory effect of downregulating G protein-coupled receptor class C group 5 member A expression on lipopolysaccharide-induced inflammatory response in human gingival fibroblasts]

    < GPCR News < GPCRs in Oncology and Immunology [Inhibitory effect of downregulating G protein-coupled receptor class C group 5 member A expression on lipopolysaccharide-induced inflammatory response in human gingival fibroblasts] Published date March 27, 2024 Abstract "Objective: To clarify the effect and the mechanism of G protein-coupled receptor class C group 5 member A (GPRC5A) on lipopolysaccharide (LPS)-induced inflammatory response in human gingival fibroblasts (GFs), thus to provide a foundation for delving into the role of G protein coupled receptor (GPCR) in periodontitis. Methods: Gingival tissue samples were collected from 3 individuals periodontally healthy (health group) and 3 patients with periodontitis (periodontitis group) in Shandong Stomatological Hospital from December 2022 to February 2023. The expressions of GPRC5A of the two groups were detected by immunohistochemistry staining. GFs used in this study were isolated from a portion of gingiva for the extraction of impacted teeth in Shandong Stomatological Hospital from December 2022 to February 2023. GFs were isolated with enzymic digestion and transfected with 30, 50 and 80 μmol/L small interfering RNA-GPRC5A (siGPRC5A) or small interfering RNA-negative control (siNC), regarded as the experimental group and the negative control one, respectively. The silencing efficiency of siGPRC5A was evaluated by real-time fluorescence quantitative PCR (RT-qPCR). Experiments were then conducted using these cells which were divided into four groups of negative control (NC), LPS, siGPRC5A+LPS and siGPRC5A. The mRNA and protein levels of GPRC5A in GFs under 1 mg/L LPS-induced GFs inflammatory state were evaluated by RT-qPCR and Western blotting analysis after GPRC5A knockdown. RT-qPCR was used to detect the gene expression levels of the inflammatory cytokines in GFs induced by LPS, namely, interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, prostaglandin endoperoxide synthase 2 (PTGS2) after GPRC5A knockdown. Western blotting analysis and immunofluorescence staining were used to further investigate the activation of nuclear factor-kappa B (NF-κB) signaling pathway. Results: Immunohistochemistry staining showed that the expression of GPRC5A in gingival tissues of periodontitis group (0.132±0.006) increased compared with that in periodontally healthy group (0.036±0.019) (t=8.24, P=0.001). Meanwhile, RT-qPCR results showed that the gene expression levels of GPRC5A at different time point (2, 6, 12, 24 h) in LPS-induced GFs (0.026±0.002, 0.042±0.005, 0.004±0.000, 0.016±0.000) were upregulated compared with those in the NC group (0.004±0.000, 0.004±0.000, 0.002±0.000, 0.007±0.000) (all P<0.001), respectively, and peaked at 6 h. The 50 μmol/L group displayed the most significant decrease in GPRC5A expression (31.16±3.29) compared with that of the NC group (100.00±4.88) (F=297.98, P<0.001). The results of RT-qPCR and Western blotting analysis showed that siGPRC5A (0.27±0.03, 0.71±0.00) suppressed the expressions of GPRC5A at both gene and protein levels, while LPS (1.30±0.10, 1.43±0.03) was able to promote the expressions of GPRC5A compared with those of the NC group (1.00±0.01, 1.00±0.00)(all P<0.001). The siGPRC5A+LPS group (0.39±0.03, 1.06±0.16) also inhibited the increase of GPRC5A at both gene and protein levels induced by LPS (1.30±0.10, 1.43±0.03) (F=208.38, P<0.001; F=42.04, P<0.001). RT-qPCR results showed that the expressions of IL-8, IL-1β, IL-6, TNF-α, and PTGS2 at the gene level in LPS group were highly increased compared with those in the NC group (all P<0.001). siGPRC5A significantly suppressed LPS-induced expressions of these inflammatory cytokines in GFs (all P<0.001). Western blotting analysis showed that the levels of p65 and IκBα protein phosphorylation in the LPS group were highly increased compared with those in the NC group, and siGPRC5A could effectively suppressed LPS-induced protein phosphorylation (all P<0.01). Furthermore, immunofluorescence staining showed that NF-κB p65 in the control group was mainly concentrated in the cytoplasm, and partially translocated to the nucleus under the stimulation of LPS. siGPRC5A was able to inhibit LPS-induced intranuclear translocation of p65 to a certain extent. Conclusions: GPRC5A expression was upregulated in periodontitis, and GPRC5A knockdown inhibited LPS-induced inflammation. Moreover, GPRC5A played a role in inflammation regulation by interacting with NF-κB signaling pathway." Authors Y H Hu , L L Shang , S H Ge 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 >

  • SSTR2 positively associates with EGFR and predicts poor prognosis in nasopharyngeal carcinoma

    < 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 >

  • Breakfast 2

    Retreat 2023 About Program Registration Logo Contest Committee Sponsors GPCR Retreat Program < Back to schedule Breakfast 2 Date & Time Saturday, November 4th / 7:30 AM 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

  • G Proteins and GPCRs in Cancer: Novel Precision Targeted and Immunotherapies

    Retreat 2023 About Program Registration Logo Contest Committee Sponsors GPCR Retreat Program < Back to schedule G Proteins and GPCRs in Cancer: Novel Precision Targeted and Immunotherapies Date & Time Friday, November 3rd / 3:30 PM Abstract Coming Soon About J. Silvio Gutkind "Dr. Gutkind is a Distinguished Professor and Chair of the Department of Pharmacology, School of Medicine, and Associate Director for Basic Science at the Moores Cancer Center, University of California San Diego (UCSD). He served as Branch Chief at NIDCR, NIH, since 1998 until his recruitment to UCSD in 2015. His research team has pioneered the study of G proteins and G protein coupled receptors (GPCRs) in human malignancies. He is exploiting the emerging information on dysregulated signaling circuitries and individual genomic and molecular alterations to develop new precision cancer treatments, and to identify novel multimodal strategies to enhance the response to cancer immunotherapies." J. Silvio Gutkind on the web Gutkind Lab – UC San Diego Moores Cancer Center Gutkind Lab publications Pubmed LinkedIn Twitter UCSD Moores Cancer Center 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

  • Trainee Symposium II

    Retreat 2023 About Program Registration Logo Contest Committee Sponsors GPCR Retreat Program < Back to schedule Trainee Symposium II Date & Time Thursday, November 2nd / 3:00 PM - 4:00 PM Title: Linking Proteinase Activated Receptor (PAR) Cleavage to Osteoarthritis (OA) Severity About Amr Mousa "I am currently a Ph.D. student at the Schulich School of Medicine and Dentistry, Western University, researching the molecular mechanisms of Proteinase-Activated Receptors (PARs) in osteoarthritis. I got my Bachelor's in Pharmacy from Minia University in 2011 and began my career as a teaching and research assistant in Pharmacology and Toxicology. Later, I completed my Master's degree in Pharmacology at Minia University, focusing on hydrogen sulfide's role in hypertension-induced endothelial dysfunction. In November 2021, I joined Dr. Ramachandran's lab as a visiting graduate student, and in September 2022, I enrolled in the direct-entry Physiology and Pharmacology Ph.D. program with a specialization in musculoskeletal health research (CMHR). During my short academic journey, I was awarded the Young Investigator Transdisciplinary Research Award (2022-2023 and 2023-2024) from the bone and joint institute, Western University and the New Student Poster Award (2022). I also received the Scientific Excellence and Publication Award from Minia University for the years 2022 and 2023." Amr Mousa on the web Google Scholar Dr. GPCR Title: Balancing G Protein Selectivity and Efficacy in the Adenosine A2A Receptor About Louis-Philippe Picard "I earned my Ph.D. in Biochemistry, working under the guidance of Dr. Michel Bouvier, at the University of Montreal from 2015 to 2019. Currently, I am engaged in postdoctoral research in the laboratory of Dr. Scott Prosser. My primary research focus lies in gaining deeper insights into the structural mechanisms governing G protein-coupled receptors (GPCRs) and G protein activation. I employ a multidisciplinary approach that combines molecular pharmacology, biochemical assays, and biophysical techniques to unravel the intricacies of these processes." Louis-Philippe Picard on the web Google Scholar Dr. GPCR Title: Development of a Transgenic Mouse Platform for the Detection of Endogenous G protein Activity About Remi Janicot "After graduating as an undergrad from Ursinus College, I joined the Johns Hopkins School of Medicine to work as a lab tech in a neurophysiology lab investigating mechanisms behind pediatric epilepsy disorders. I then joined Boston University to pursue my scientific career as PhD student and joined the lab of Dr. Mikel Garcia-Marcos which investigates GPCR and G protein signaling" Remi Janicot on the web Boston University Dr. GPCR Title: Antibodies Expand the Scope of Angiotensin Receptor Pharmacology About Meredith Skiba "Meredith completed her PhD in Biological Chemistry with Janet Smith at the University of Michigan studying the biosynthesis of polyketide natural products using x-ray crystallography. She then joined Andrew Kruse’s lab for her postdoc in 2018 where she has employed protein engineering, receptor pharmacology, and structural biology to study how different types of ligands modulate angiotensin receptor signaling." Meredith Skiba on the web Harvard University University of Michigan 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

  • Proteogenomic landscape and clinical characterization of GH-producing pituitary adenomas/somatotroph pituitary neuroendocrine tumors

    < GPCR News < GPCRs in Oncology and Immunology Proteogenomic landscape and clinical characterization of GH-producing pituitary adenomas/somatotroph pituitary neuroendocrine tumors Published date November 1, 2022 Abstract The clinical characteristics of growth hormone (GH)-producing pituitary adenomas/somatotroph pituitary neuroendocrine tumors (GHomas/somatotroph PitNETs) vary across patients. In this study, we aimed to integrate the genetic alterations, protein expression profiles, transcriptomes, and clinical characteristics of GHomas/somatotroph PitNETs to identify molecules associated with acromegaly characteristics. Targeted capture sequencing and copy number analysis of 36 genes and nontargeted proteomics analysis were performed on fresh-frozen samples from 121 sporadic GHomas/somatotroph PitNETs. Targeted capture sequencing revealed GNAS as the only driver gene, as previously reported. Classification by consensus clustering using both RNA sequencing and proteomics revealed many similarities between the proteome and the transcriptome. Gene ontology analysis was performed for differentially expressed proteins between wild-type and mutant GNAS samples identified by nontargeted proteomics and involved in G protein-coupled receptor (GPCR) pathways. The results suggested that GNAS mutations impact endocrinological features in acromegaly through GPCR pathway induction. ATP2A2 and ARID5B correlated with the GH change rate in the octreotide loading test, and WWC3, SERINC1, and ZFAND3 correlated with the tumor volume change rate after somatostatin analog treatment. These results identified a biological connection between GNAS mutations and the clinical and biochemical characteristics of acromegaly, revealing molecules associated with acromegaly that may affect medical treatment efficacy. Authors Azusa Yamato, Hidekazu Nagano, Yue Gao, Tatsuma Matsuda, Naoko Hashimoto, Akitoshi Nakayama, Kazuyuki Yamagata, Masataka Yokoyama, Yingbo Gong, Xiaoyan Shi, Siti Nurul Zhahara, Takashi Kono, Yuki Taki, Naoto Furuki, Motoi Nishimura, Kentaro Horiguchi, Yasuo Iwadate, Masaki Fukuyo, Bahityar Rahmutulla, Atsushi Kaneda, Yoshinori Hasegawa, Yusuke Kawashima, Osamu Ohara, Tetsuo Ishikawa, Eiryo Kawakami, Yasuhiro Nakamura, Naoko Inoshita, Shozo Yamada, Noriaki Fukuhara, Hiroshi Nishioka, Tomoaki Tanaka 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 >

  • Ep 127 with Dr. Evi Kostenis

    Dr. GPCR Podcast << Back to podcast list Dr. Evi Kostenis About Dr. Evi Kostenis "Pharmacist by training - PhD in Pharmacology - Postdoc at the NIH with Dr. Juergen Wess - Postdoc and Group leader in Aventis, now Sanofi, Frankfurt, Germany - Head of in vitro Pharmacology at 7TM Pharma in Denmark; Full professor, department chair and director of the institute for pharmaceutical Biology at the University of Bonn. Research interests: Signaling mechanisms involving GPCRs and heterotrimeric G proteins" Dr. Evi Kostenis on the web University of Bonn 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 >>

  • Ep 16 with Dr. Aaron Sato

    Dr. GPCR Podcast << Back to podcast list Dr. Aaron Sato About this episode In this episode of the Dr. GPCR Podcast , I spoke to Dr. Aaron Sato from Twist Biopharma , a vertical within Twist Bioscience . Aaron is currently the Chief Scientific Officer and VP of Protein Engineering. He earned his Ph.D. at the Massachusetts Institute of Technology, where he studied MHC class II structure-function relationships. His path led him to work in an industry where he assumed various responsibilities and roles in the antibody space. Aaron has a proven track record as a biologics leader as he led teams to discover and develop novel first-in-class antibody therapeutics. Dr. Sato published over 30 peer-reviewed papers and contributed to 40 issued patents in the antibody space. During our time together, Aaron and I discussed how using Twist Bioscience’s proprietary technology to manufacture DNA at a scale, the team saw an opportunity to tackle the challenge of identifying novel functional antibodies targeting GPCRs by incorporating these natural binding partners into Twist’s antibody library design. We’d like to extend a special thanks to Twist Biopharma for sponsoring this episode of the Dr. GPCR podcast. Dr. Aaron Sato on the web LinkedIn Twitter Google Scholar Twist Bioscience Twist Biopharma 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 >>

  • Ep 143 with Dr Davide Calebiro

    Dr. GPCR Podcast << Back to podcast list Dr. Davide Calebiro About Dr. Davide Calebiro "Davide Calebiro is Chair of Molecular Endocrinology and Wellcome Trust Senior Research Fellow at the Institute of Metabolism and Systems Research (IMSR) of the University of Birmingham and Co-Director of the Centre of Membrane Proteins and Receptors (COMPARE) of the Universities of Birmingham and Nottingham. He studied Medicine in Milan and Stockholm, and obtained a PhD in Molecular Medicine and a Clinical Specialisation in Endocrinology and Metabolic Disease from the University of Milan. Between 2009 and 2017, he was a Group Leader at the Institute of Pharmacology and Toxicology and Rudolf Virchow Center of the University of Würzburg, Germany. He leads a multidisciplinary research team comprising biologists, chemists, physicists, engineers and computer scientists focusing on the basic mechanisms of G protein-coupled receptor (GPCR) signalling and their alterations in endocrine, metabolic and cardiovascular diseases. To study GPCR signalling, they develop and use innovative optical methods based on FRET and single-molecule microscopy, which allow them to directly observe signalling events in living cells and tissues with unprecedented spatiotemporal resolution. His major scientific contributions include the discovery that GPCRs are not only active at the plasma membrane but also at intracellular sites and that these receptors interact among themselves and with other membrane proteins to form dynamic nanodomains at the plasma membrane. Davide’s work has been published in prestigious scientific journals such as Nature, Cell, New England Journal of Medicine, Journal of Clinical Investigation, PLoS Biology, PNAS, Nature Communications and Science Advances, attracting several prizes and awards. He has served on multiple panels and committees, including the ENDO Annual Meeting Steering Committee and the MRC Molecular & Cellular Medicine Board." Dr. Davide Calebiro on the web University of Birmingham Twitter 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 >>

  • Ep 17 with Dr. Yamina Berchiche

    Dr. GPCR Podcast << Back to podcast list Dr. Yamina Berchiche About this episode GPCRs have played a central role in my scientific career ever since I took Dr. Michel Bouvier’s class as an undergraduate student at the University of Montreal in early 2000. During the past 2 decades, my research mainly focused on chemokine receptor structure/function relationships. For the purposes of this presentation, I will walk you through my various career experiences and include the skills I learned during each experience, which ultimately led me to found Dr. GPCR. Last, I will give an overview of the various programs we established at Dr. GPCR, present our team as well as provide you with a sneak peek of our future podcast guests and more. I gave a talk on October 12th at the 3rd ERNEST meeting about the Dr.GPCR Ecosystem . I want to say thank you to the ERNEST meeting organizers for the invitation with special thanks to Dr. Martha Summer and Dr. Alexander Hauser , and Luise Wagner . For more information about the ERNEST network, visit https://ernest-gpcr.eu/ . Dr. Yamina Berchiche on the web D r. GPCR Ecosystem Member Website LinkedIn Publications Twitter Facebook 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 >>

  • Ep 136 with Murat Tunaboylu & Ben Holland

    Dr. GPCR Podcast << Back to podcast list Murat Tunaboylu & Ben Holland About Murat Tunaboylu "Murat Tunaboylu, Antiverse's CEO, has a software engineering and bioinformatics background. Mid-career, he has worked in finance and developed high-frequency trading systems. After switching to biotech, Murat has built cell imaging software and lab robots to accelerate cancer research and automated Thermo Fisher Scientific’s gene synthesis workflows. He has co-founded consultancy and biotech companies Svarlight and Antiverse. His current focus is to realise Antiverse’s mission: engineering the future of drug discovery." Murat Tunaboylu on the web Antiverse DSV Future of Drug Discovery Podcast Twist Bioscience LinkedIn Twitter Dr. GPCR About Ben Holland "Ben gained his masters in Engineering Science from Oxford, taking a specialisation in information engineering. Following this, he joined an early-stage medical device start-up and in 5 years was responsible for project R&D and managing a focused development team, pursued international strategic partnerships, managed IP matters, helped establish a manufacturing line in Malaysia and is named as inventor on several patents. He then returned to information engineering and has been working in machine learning for nearly 10 years, applying it to antibody generation, analysis, and property prediction since 2017" Ben Holland on the web Antiverse The Antibody Society YT 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 >>

  • Ep 18 with Dr. Yamina Berchiche

    Dr. GPCR Podcast << Back to podcast list Dr. Yamina Berchiche About this episode Listen to this fantastic round table discussion that I had the privilege to moderate with Alexander Hauser . Our guests were Maria Waldhoer , Tudor I. Oprea , Thomas Sakmar , Aurelien Rizk & Yaroslav Nikolaev . The explosion of biomedical data such as in genomics, structural biology, and pharmacology can provide new opportunities to improve our understanding of human physiology and disease. In recent years, machine learning (ML) and artificial intelligence (AI) methods have received a significant boost in attention. ML/AI can be powerful for identifying abstract patterns within large data where traditional methods would be oblivious to. This comes without the need for manual feature engineering as systems can learn through implicit rules from the data provided. G protein-coupled receptors (GPCRs) mediate a vast variety of critical biological processes and provide an ideal case study for quantitative, and multi‐scale integration of these amounts of data to gain novel insights into receptor biology. How can we best leverage these exciting new techniques in areas such as protein structure prediction, bioactive ligand discovery, in-vivo translation ability, or in our understanding of signaling determinants? Here, we would like to discuss the opportunities, weaknesses, and advantages of these new technologies, which may contribute to probe our favorite targets at all scales. For more information on the ERNEST network, visit https://ernest-gpcr.eu/ . Dr. Yamina Berchiche on the web Website LinkedIn Publications Twitter Facebook 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 >>

  • Ep 59 with Dr. Nicola J. Smith

    Dr. GPCR Podcast << Back to podcast list Dr. Nicola J. Smith About Dr. Nicola J. Smith Dr. Nicola J Smith is an expert in molecular pharmacology with a track record in exploring GPCR structure-function relationships in the context of cardiovascular disease and metabolic disorders. She is a National Heart Foundation of Australia Future Leader Fellow and runs a laboratory of 7 Ph.D. and Honours students at UNSW Sydney, where she has recently been promoted to Associate Professor. Most recently, Dr. Smith’s team has made advances in the understanding of how an orphan GPCR exerts its effects both in vitro (cell culture and ex vivo models) and in vivo (measures of physiological and pathological cardiometabolic function in unconscious and conscious mice). Together with Irina Kufareva , UCSD, her team developed a novel approach to identifying ligands for orphan GPCRs by developing a powerful new computational tool for identifying ‘surrogate’ ligands (borrowed from other receptors) for orphan GPCRs, named GPCR-CoINPocket. Her career goal is to leverage this expertise to establish a research program that takes orphan GPCRs from ‘locked’, inaccessible receptors to well-characterized and understood ‘unlocked’ therapeutic targets with high-affinity ligands. Dr. Nicola J. Smith on the web UNSW Sydney LinkedIn Retraction Watch Twitter 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 >>

  • Ep 05 with Dr. Terry Hébert

    Dr. GPCR Podcast << Back to podcast list Dr. Terry Hébert About this episode Dr. Terry Hébert is a Professor within the Department of Pharmacology & Therapeutics at McGill University. Much of his work is based on GPCR signaling in the context to cardiovascular diseases. In this special episode of the Dr.GPCR podcast , we re-connected with Dr. Terry Hebert to chat about how he and his team has been adapting to the new reality of working remotely. Terry tells us about the importance of adapting, communicating, and being mindful of those around us. Dr. Terry Hébert on the web Terry Hébert | Institute of Health Sciences Education Hébert Lab LinkedIn Hébert Lab The GPCR Consortium PubMed Dr. GPCR Ecosystem 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 >>

  • Ep 04 with Dr. Graciela Pineyro

    Dr. GPCR Podcast << Back to podcast list Dr. Graciela Pineyro About this episode Dr. Graciela Pineyro’s love for GPCR pharmacology started in Uruguay where she first worked on the serotonin receptors. This interest in research and pharmacology took Graciela to Canada where she stayed ever since she arrived for her Ph.D. work. Graciela has done extensive work on the molecular pharmacology of opioid receptors, exploring their signaling, trafficking, and their ability to activate different signaling pathways and signaling bias. Today, Graciela and her team’s efforts are directed towards the characterization of the pharmacological properties of cannabinoids in conjunction with terpenes for pain relief. 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 >>

  • GPR15 expressed in T lymphocytes from RA patients is involved in leukocyte chemotaxis to the synovium

    < 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 >

  • Metallo-protease Peptidase M84 from Bacillusaltitudinis induces ROS-dependent apoptosis in ovarian cancer cells by targeting PAR-1

    < 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 >

  • Molecular characterization of breast cancer cell pools with normal or reduced ability to respond to progesterone: a study based on RNA-seq

    < 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 >

  • Ep 21 with Dr. Maria Waldhoer

    Dr. GPCR Podcast << Back to podcast list Dr. Maria Waldhoer About this episode Dr. Maria Waldhoer is originally from Austria. She earned her M.Sc. in Zoology and Neurobiology before completing a Ph.D. in Biology and Pharmacology at the University of Vienna. GPCRs led Maria to Thue W. Schwartz’s lab in Copenhagen where she completed her postdoctoral training. After working in the US and at the University in Graz in Austria, Maria worked several years at Novo Nordisk before joining InterAx Biotech in Switzerland as their Chief Scientific Officer. Even though Maria stumbled upon the GPCR field, her 20 years in both academia and in the industry working on GPCRs make her a strong and dedicated scientific leader. Dr. Maria Waldhoer on the web LinkedIn InterAx Biotech 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 >>

  • Ep 71 with Dr. Jean Martin Beaulieu

    Dr. GPCR Podcast << Back to podcast list Dr. Jean Martin Beaulieu About Dr. Jean Martin Beaulieu Dr. Beaulieu received a Ph.D. in Neurological Sciences from McGill University and completed his post-doctoral training at Duke University. Prior to his recruitment Dr. Beaulieu was an associate professor and Canada Research Chair (Tier2) in the Department of Psychiatry and Neuroscience at Laval University. Dr. Beaulieu’s research is aimed at understanding how cellular and molecular mechanisms regulated by psychoactive drugs intersect with genetic risk factors for mental illnesses such as schizophrenia, depression, and bipolar disorder. Dr. Beaulieu has pioneered work establishing a role for Beta-arrestin signaling in the brain in vivo and has established its importance in D2 dopamine receptors (D2R) functions. These receptors belong to the super-family of G-protein coupled receptors (GPCR), the major molecular target for drug development. In particular, D2R is the main pharmacological target of antipsychotic drugs prescribed for schizophrenia and bipolar disorders. Work by the Beaulieu Lab has demonstrated that mood stabilizer drugs (e.g. lithium) used for bipolar disorder therapy target signaling mechanisms regulated by dopamine receptors, thus providing a framework to understand how different drug classes can engage overlapping cellular mechanisms to exert their action. The Beaulieu group is presently investigating how cell surface express proteins can act as allosteric modulators of D2R signaling and explores the potential usefulness of beta-arrestins for the development of new pharmaceutical agents. Translational validation is important to validate findings obtained from experimental models research and bridge the gap between bench and bedside. Working in collaboration with geneticists, the Beaulieu-Lab has identified interactions between cellular mechanisms engaged by D2R and psychiatric drugs with genetic risk factors implicated in schizophrenia by large whole-genome association studies (GWAS) in humans. These investigations have led to the identification of an RNA binding protein (FXR1P) involved in the regulation of protein synthesis as a potential downstream effector of the action of mood stabilizers and other psychoactive drugs. In addition to basic research, the Beaulieu group is also actively implicated in translational research and industry collaboration to develop new drugs and drug development technology. Dr. Jean Martin Beaulieu on the web University of Toronto Google Scholar LinkedIn ResearchGate 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 >>

  • Ep 79 with Dr. Graeme Milligan

    Dr. GPCR Podcast << Back to podcast list Dr. Graeme Milligan About Dr. Graeme Milligan Professor Graeme Milligan is Gardiner Professor of Biochemistry, Dean of Research, and Deputy Head of the College of Medical, Veterinary, and Life Sciences at the University of Glasgow. His main research group centers on the function, structure, and regulation of G protein-coupled receptors (GPCRs) and their interacting proteins. His experience also includes translating knowledge generated into the selection of targets, screening, and identification of small molecule regulators of these proteins, and progressing such ligands in drug development programs. Prof. Milligan has published more than 550 peer-reviewed articles and his research has been cited more than 35,000 times. He was elected to the Fellowship of the Royal Society of Edinburgh in 1998 and to the Fellowship of the Academy of Medical Sciences in 2016. Prof. Milligan is the co-founder of both Caldan Therapeutics (2015) which discovers novel therapeutics for metabolic diseases including Type 2 Diabetes and other indications including non-alcoholic steatohepatitis (NASH) and inflammatory diseases and Keltic Pharma Therapeutics (2020) which is developing new treatments for malaria. Dr. Graeme Milligan on the web University of Glasgow ResearchGate PubMed Orcid Google Scholar LinkedIn Dr. GPCR Ecosystem Thanks for listening to this podcast episode This short survey will help us understand your needs to bring you exciting and informative content; this short survey should take 5 minutes to fill. Listen and subscribe to where you get your podcasts. << Previous Podcast Episode Next Podcast Episode >>

  • Ep 134 with Dr. Neil Grimsey

    Dr. GPCR Podcast << Back to podcast list Dr. Neil Grimsey About Dr. Neil Grimsey " During my postdoctoral studies at USCD, I discovered a novel GPCR-dependent atypical kinase activation mechanism that drives vascular edema and inflammation. These studies shaped my future goals as an Assistant Professor in the College of Pharmacy at the University of Georgia Athens. My group studies the spatiotemporal dynamics of atypical inflammation and the control of disease progression. We have developed an array of fluorescent biosensors to map kinase activity in living cells and are exploring innovative techniques to delineate the molecular dynamics of atypical p38 and suppress kinase activation. To further define the role of atypical p38 signaling responses we are studying how atypical p38 controls the onset and pathogenesis of acute lung injury, retinal vasculopathies, and infections. " Dr. Neil Grimsey on the web LinkedIn University of Georgia Google Scholar X (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 >>

  • 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

    < 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 >

  • 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

    < 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 >

  • Ep 40 with Dr. Brian Bender

    Dr. GPCR Podcast << Back to podcast list Dr. Brian Bender About Dr. Brian Bender Dr. Bender completed his undergraduate studies at Colgate University in upstate New York with a degree in Biochemistry. Between undergraduate and graduate school Brian worked as a technician in an academic lab before moving to Nashville, TN for graduate work at Vanderbilt University where he joined the Department of Pharmacology. Brain’s work there primarily focused on structure prediction of GPCRs from sparse experimental data. He then moved to the University of California in San Francisco to continue his training as a postdoctoral researcher where he used structural models of GPCRs to virtually screen large compound libraries with the goal of finding new chemical matter to probe understudied and orphan receptors. Brian is involved in organizing the GRC/GRS Molecular Pharmacology meeting, which has been postponed to 2023. Brian is one of the organizers of the upcoming Transatlantic ECI GPCR Symposium . Dr. Brian Bender on the web LinkedIn Twitter ResearchGate Dr.GPCR Member 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 >>

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