Paul Insel, M.D.
Distinguished Professor Emeritus
of Pharmacology and Medicine
Paul Insel, Ph.D.
Distinguished Professor Emeritus of Pharmacology and Medicine
G-protein coupled receptors (GPCR), heterotrimeric G proteins, G-protein-regulated effectors and targets. Current work emphasizes GPCR expression by individual cell types and the contribution of particular GPCRs to cellular responses, in particular, in cells (especially cancer cells and cancer-associated fibroblasts) in the tumor microenvironment. We focus on previously unrecognized GPCRs as regulators of cell function and as novel therapeutic targets. Our current emphasis is on pancreatic cancer. We use molecular/cell biological, biochemical, and pharmacological approaches. Other efforts include the identification of therapeutic approaches for patients with COVID-19 based on its pathobiology in the hosts.
Insel PA, Sriram K, Wiley SZ, Katakia T, McCann T, Yokouchi H, Zhang L, Corriden R, Liu D, Feigin ME, French RP, Lowy AM, Murray F. GPCRomics: GPCR expression in cancer cells and tumors identifies new, potential biomarkers and therapeutic targets. Front Pharmacol. 9: 431 (2018).
Wiley SZ, Sriram K, Liang W, Chang SE, French R, McCann T, Sicklick J, Nishihara H, Lowy AM, Insel PA. GPR68, a proton-sensing GPCR, mediates interaction of cancer-associated fibroblasts and cancer cells. FASEB J 32: 1170-83 (2018)
Sriram K, Moyung K, Corriden R, Carter H. Insel PA. GPCRs show widespread differential mRNA expression and frequent mutation and copy number variation in solid tumors. PLoS Biol 17(11):e3000434. doi: 10.1371/journal.pbio.3000434 (2019)
Sriram K, Salmerón C, Wiley SZ, Insel PA, GPCRs in pancreatic adenocarcinoma: Contributors to tumour biology and novel therapeutic targets. Brit J Pharmacol. 177: 2434-2455 (2020).
Insel PA, Sriram K, Salmerón C, Wiley SZ. Proton-sensing G protein-coupled receptors: detectors of tumor acidosis and candidate drug targets. Future Med Chem 12: 523-532. (2020)
Sriram K, Insel PA. Risks of ACE inhibitor and ARB usage in COVID-19: Evaluating the evidence. Clin Pharmacol Ther. 108: 236-41 (2020)
Sriram K and Insel PA. A hypothesis for pathobiology and treatment of COVID-19: The centrality of ACE1/ACE2 imbalance. Brit. J Pharmacol 177: 4825-4844 (2020)
Chinn AM, Insel PA. Cyclic AMP in dendritic cells: A novel potential target for disease-modifying agents in asthma and other allergic disorders. Brit J Pharmacol 177: 3363-3377 (2020)
Sriram K and Insel PA. Proteinase-activated receptor 1: A target for repurposing in the treatment of COVID-19? Brit J Pharmacol 177: 4971-4974 (2020)
Sriram K, Loomba R, Insel PA. Targeting the renin-angiotensin signaling pathway in COVID-19: Unanswered questions, opportunities and challenges. Proc Nat Acad Sci USA 117: 29274-20282 (2020)
Sriram K, Insel PA. Inflammation and thrombosis in COVID-9 pathophysiology: Proteinase-activated and purinergic receptors as drivers and candidate therapeutic targets. Physiol. Rev 101: 545-567 (2021)