Morgan, Noel - University of Exeter

个人简介

Noel Morgan began his research career studying islet biology at University of Leicester and then undertook postdoctoral work on the hormonal control of liver glycogenolysis at Vanderbilt University (Nashville, TN). He subsequently developed an independent research programme in islet biology while on the faculty of Keele University (UK). Noel was awarded the inaugural Albert E. Renold Fellowship of EASD in 1990 to work in the laboratory of Robert J Lefkowitz (2012 Nobel laureate) at Duke University, Durham, NC studying adrenoceptor signalling in beta-cells. He was appointed to a Personal Chair at Keele University in 1993 and moved to University of Exeter, in 2002, as Professor of Endocrine Pharmacology. At Exeter, his group has pursued parallel studies on signaling mechanisms regulating β-cell function and viability as well as factors that underlie the loss of β-cells in type 1 diabetes. The latter has been sustained by a long and productive collaboration with Prof Alan Foulis and, together with Dr Sarah Richardson, the team has contributed to the understanding of insulitis in humans and to the role of enteroviruses as potential mediators of islet autoimmunity.

研究领域

Professor Morgan's team has research interests which centre around the mechanisms that lead to beta-cell dysfunction and death in both type 1 and type 2 diabetes. Their work in type 1 diabetes makes use of a unique cohort of pancreas samples recovered from patients who died soon after diagnosis, to study the natural history of the disease. They are investigating the immune cell composition of the infiltrate that is associated with beta-cell loss (known as “insulitis”) and are also studying the possible involvement of an enteroviral infection as a mediator of islet autoimmunty. The anti-viral mechanisms that become activated in beta-cells during such infections are a particular focus of investigation. In addition, they employ cell culture models to study the role of fatty acids as regulators of beta-cell viability. Patients with type 2 diabetes often have elevated levels of long chain free fatty acids and these can cause beta-cell death. Their work has revealed that the effects of such molecules on viability are influenced greatly by the chain length and degree of unsaturation of the fatty acid molecules. Indeed, it is evident that long chain saturated species are frequently cytotoxic whereas the equivalent long chain unsaturates (both mono- and poly-) are well tolerated and can even be cytoprotective. They are currently studying the mechanisms involved. A third area of interest is the signalling pathways used by anti-inflammatory cytokines, such as interleukin-4 and interleukin-13 to promote beta-cell viability. These molecules regulate the activity of a family of transcription factors (STATs) and they are examining exactly how various STAT isoforms become activated and the mechanisms that then lead to improved viability. In parallel, they are also studying the pro-apoptotic actions of other STAT family members to understand how these proteins cause differential effects on beta-cell viability. Professor Morgan gives an overview of his research in the video below, in a joint presentation with Kyle Wedgwood, filmed at the Living Systems Institute Symposium 2016.

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Wagner FF, Lundh M, Kaya T, McCarren P, Zhang YL, Chattopadhyay S, Gale JP, Galbo T, Fisher SL, Meier BC, et al (2016). An Isochemogenic Set of Inhibitors to Define the Therapeutic Potential of Histone Deacetylases in β-Cell Protection. ACS Chem Biol, 11(2), 363-374. Abstract. Author URL. Article has an altmetric score of 1 Leete P, Willcox A, Krogvold L, Dahl-Jørgensen K, Foulis AK, Richardson SJ, Morgan NG (2016). Differential Insulitic Profiles Determine the Extent of β-Cell Destruction and the Age at Onset of Type 1 Diabetes. Diabetes, 65(5), 1362-1369. Abstract. Author URL. Full text. Article has an altmetric score of 175 Richardson SJ, Rodriguez-Calvo T, Gerling IC, Mathews CE, Kaddis JS, Russell MA, Zeissler M, Leete P, Krogvold L, Dahl-Jørgensen K, et al (2016). Islet cell hyperexpression of HLA class I antigens: a defining feature in type 1 diabetes. Diabetologia, 59(11), 2448-2458. Abstract. Author URL. Full text. Article has an altmetric score of 25 Laiho JE, Oikarinen M, Richardson SJ, Frisk G, Nyalwidhe J, Burch TC, Morris MA, Oikarinen S, Pugliese A, Dotta F, et al (2016). Relative sensitivity of immunohistochemistry, multiple reaction monitoring mass spectrometry, in situ hybridization and PCR to detect Coxsackievirus B1 in A549 cells. Journal of Clinical Virology, 77, 21-28. Full text. Article has an altmetric score of 1 Krogvold L, Edwin B, Buanes T, Frisk G, Skog O, Anagandula M, Korsgren O, Undlien D, Eike MC, Richardson SJ, et al (2015). Detection of a low-grade enteroviral infection in the islets of langerhans of living patients newly diagnosed with type 1 diabetes. Diabetes, 64(5), 1682-1687. Abstract. Author URL. Full text. Article has an altmetric score of 56 Marroqui L, Lopes M, dos Santos RS, Grieco FA, Roivainen M, Richardson SJ, Morgan NG, Op de Beeck A, Eizirik DL (2015). Differential cell autonomous responses determine the outcome of coxsackievirus infections in murine pancreatic α and β cells. Elife, 4 Abstract. Author URL. Article has an altmetric score of 2 Taniguchi K, Russell MA, Richardson SJ, Morgan NG (2015). The subcellular distribution of cyclin-D1 and cyclin-D3 within human islet cells varies according to the status of the pancreas donor. Diabetologia Abstract. Full text. Article has an altmetric score of 6 Taniguchi K, Russell MA, Richardson SJ, Morgan NG (2015). The subcellular distribution of cyclin-D1 and cyclin-D3 within human islet cells varies according to the status of the pancreas donor. Diabetologia, 58(9), 2056-2063. Abstract. Article has an altmetric score of 6 Flanagan SE, Haapaniemi E, Russell MA, Caswell R, Lango Allen H, De Franco E, McDonald TJ, Rajala H, Ramelius A, Barton J, et al (2014). Activating germline mutations in STAT3 cause early-onset multi-organ autoimmune disease. Nat Genet, 46(8), 812-814. Abstract. Author URL. Full text. Article has an altmetric score of 11 Arif S, Leete P, Nguyen V, Marks K, Nor NM, Estorninho M, Kronenberg-Versteeg D, Bingley PJ, Todd JA, Guy C, et al (2014). Blood and islet phenotypes indicate immunological heterogeneity in type 1 diabetes. Diabetes, 63(11), 3835-3845. Abstract. Author URL. Full text. Article has an altmetric score of 17 Richardson SJ, Leete P, Dhayal S, Russell MA, Oikarinen M, Laiho JE, Svedin E, Lind K, Rosenling T, Chapman N, et al (2014). Detection of enterovirus in the islet cells of patients with type 1 diabetes: what do we learn from immunohistochemistry? Reply to Hansson SF, Korsgren S, Pontén F et al [letter]. Diabetologia, 57(3), 647-649. Author URL. Full text. Morgan NG, Richardson SJ (2014). Enteroviruses as causative agents in type 1 diabetes: loose ends or lost cause?. Trends Endocrinol Metab, 25(12), 611-619. Abstract. Author URL. Full text. Article has an altmetric score of 11 Richardson SJ, Leete P, Dhayal S, Russell MA, Oikarinen M, Laiho JE, Svedin E, Lind K, Rosenling T, Chapman N, et al (2014). Evaluation of the fidelity of immunolabelling obtained with clone 5D8/1, a monoclonal antibody directed against the enteroviral capsid protein, VP1, in human pancreas. Diabetologia, 57(2), 392-401. Abstract. Full text. Stone VM, Dhayal S, Brocklehurst KJ, Lenaghan C, Sörhede Winzell M, Hammar M, Xu X, Smith DM, Morgan NG (2014). GPR120 (FFAR4) is preferentially expressed in pancreatic delta cells and regulates somatostatin secretion from murine islets of Langerhans. Diabetologia, 57(6), 1182-1191. Abstract. Author URL. Full text. Anagandula M, Richardson SJ, Oberste MS, Sioofy-Khojine AB, Hyöty H, Morgan NG, Korsgren O, Frisk G (2014). Infection of human islets of langerhans with two strains of coxsackie B virus serotype 1: Assessment of virus replication, degree of cell death and induction of genes involved in the innate immunity pathway. Journal of Medical Virology, 86(8), 1402-1411. Abstract. Article has an altmetric score of 1 Morgan NG, Leete P, Foulis AK, Richardson SJ (2014). Islet inflammation in human type 1 diabetes mellitus. IUBMB Life, 66(11), 723-734. Abstract. Author URL. Full text. Article has an altmetric score of 1 Richardson SJ, Morgan NG, Foulis AK (2014). Pancreatic pathology in type 1 diabetes mellitus. Endocr Pathol, 25(1), 80-92. Abstract. Author URL. Full text. Bjursell M, Xu X, Admyre T, Böttcher G, Lundin S, Nilsson R, Stone VM, Morgan NG, Lam YY, Storlien LH, et al (2014). The beneficial effects of n-3 polyunsaturated fatty acids on diet induced obesity and impaired glucose control do not require Gpr120. PLoS One, 9(12). Abstract. Author URL. Article has an altmetric score of 1 Russell MA, Morgan NG (2014). The impact of anti-inflammatory cytokines on the pancreatic β-cell. Islets, 6(3). Abstract. Author URL. Full text. Article has an altmetric score of 1 Russell MA, Cooper AC, Dhayal S, Morgan NG (2013). Differential effects of interleukin-13 and interleukin-6 on Jak/STAT signaling and cell viability in pancreatic β-cells. Islets, 5(2), 95-105. Abstract. Author URL. Full text.