ISLET BIOLOGY AND ISLET TRANSPLANTATION PROGRAM
Millions of diabetics suffer an extremely poor quality of life due to complications of their disease. The challenge is in finding a cure. Progress is being made, with many routine and experimental treatment options available. One promising experimental approach is pancreatic islet cell transplantation. Islet cells are the cells in the pancreas that regulate blood sugar levels by secreting insulin. Type I diabetics are lacking this mechanism due to destruction of their own islet cells by an auto-immune response. Islet transplantation involves the removal of healthy islet cells from a deceased donor for transplantation into a diabetic recipient with the goal of providing the required insulin response to control blood sugars. There are still many obstacles to overcome before this procedure can become routine. With potential demand greatly exceeding the supply of available donor tissue, beta islet cell expansion and alternative sources of creating insulin producing cells are critical areas of research. Current activities in my lab are concentrated on these areas with particular focus on protecting islet cells after transplantation, enhancing the insulin secretory capabilities of isolated islets and investigating methodology to stimulate expansion and proliferation of beta islet cells in culture and in vivo.
D. Andrjewski, M Brown, N Ungerleider, A Burnside, A Schneyer. Activins A and B regulate fate-determining gene expression in islet cell lines and islet cells from male mice. Endocrinology. 2015 May 11:en20151167.
M. Brown, N. Ungerleider, L. Bonomi, A. Schneyer. Effects of activin A on survival, function, and gene expression of pancreatic islets from non-diabetic and diabetic human donors. Islets. 2014 Nov 2;6(5-6):e1017226. doi: 10.1080/19382014.2015.101722.
C. Kim, P. Patel, L. Gouvin, M. Brown, A. Khalil, E. Henchey, A. Heuck. N. Yadava. Comparative analysis of the mitochondrial physiology of pancreatic beta cells. Bioenergetics. 2014. March 1;3(1):110.doi:10.4172/2167-7662.1000110.
K. Gauger , L. Basso, B. Bentley, M. Brown, E. Henchey, A. Shimono, J. Wyman, S. Schneider. Mice deficient in SFRP1 exhibit increased diposity, dysrgegulated glucose metabolism and enhanced macrophage infiltration. PLosOne. 2013 Dec 5;8(12):e78320. doi: 10.1371/journal.pone.0078320.
N. Ungerleider, L. Bonomi, M. Brown, A. Schneyer. Increased activin bioavailability enhances hepatic insulin sensitivity while inducing hepatic steatosis in male mice. Endocrinology. 2013 Jun;154(6):2025-33. doi: 10.1210/en.2012-1844.
L. Bonomi, M. Brown, N. Ungerleider, M. Muse, M. Matzuk, A. Schneyer. Activin B regulates islet composition and function but not whole body glucose homeostasis or insulin sensitivity. Am J Physiol Endocrinol Metab. 2012 Sep 1;303(5):E587-96. doi: 10.1152/ajpendo.00177.2012.
M. Brown, F. Kimura, L. Bonomi, N. Ungerleider, A. Schneyer. Differential synthesis and action of TGFb superfamily ligands in mouse and rat islets. Islets. 2011.Nov/Dec;3(6):1-9.
M.Brown, L. Bonomi, F. Kumura, N. Ungerleider, A. Schneyer. Follistatin And Follistatin Like-3 Differentially Regulate Adiposity And Glucose Homeostasis. Obesity. advance online publication 5 May 2011. doi:10.1038/oby.2011.97.
A Schneyer,M Brown . Altered glucose homeostasis resulting from developmental exposures to endocrine disruptors. In: Diamanti-Kandarakis D, Gore AC (eds), Endocrine Disruptors and Puberty. Springer/Humana, 2012. doi:10.1007/978-1-60761-561-3_11.
S Morini, G Elias, M Brown, V Subbotin, C Rastellini, L Cicalese. Chronic morpho-functional damage as a consequence of transient ischemia/reperfusion injury of the small bowel. Histol Histopathol. 2010 Mar;25(3):277-86.
M. Brown, and A. Schneyer. Emerging roles for TGFb superfamily in beta-cell homeostasis.Trends in Endocrinology and Metabolism. 2010 21(7), 441-448, 2010.
S. Bradley, M. Pahari, G. Elias, M. Brown, C. Rastellini, L. Cicalese. Genetic expression profile during acute cellular rejection in clinical intestinal transplantation. Transplantation. 2008;86(7):998-1001.
S. Morini, M. Brown, L. Cicalese, G. Elias, E. Gaudio, C. Rastellini. Revascularization and remodeling of pancreatic islets grafted under the kidney capsule. Journal of Anatomy. 2007;210(5):565-77.Epub 2007 Mar 29.
G. Elias, C. Rastellini, H. Nsier, P. Nazarey, M. Brown, M. Pahari, D. Kim, L. Cicalese. Successful long term repair of hepatic artery pseudoaneurysm following liver transplantation with primary stent-grafting. Liver Transplantation. 2007;13(9):1346-8.
M.Pahari, M. Brown, G. Elias, H. Nsier, B. Banner, C. Rastellini, L. Cicalese. Development of a bio-artificial new intestinal segment using an acellular matrix scaffold. Gut. 2007;56(6):885-886.
C. Rastellini, M. Brown, L. Cicalese. Heparin-induced thrombocytopenia following pancreatectomy and islet auto-transplantation. Clinical Transplantation. 2006;20:156-158.
S.P. Bradley, C. Rastellini, M.A. Costa, T.F. Kowalik, A.B. Bloomenthal, M. Brown, L. Cicalese, G.P. Basadonna, M.E. Uknis. Gene silencing in the endocrine pancreas mediate by short-interfering RNA. Pancreas. 2005 Nov:31(4):373-379.
M.Brown, M. Braun, L. Cicalese, C. Rastellini. Effect of perioperative antioxidant therapy on suboptimal islet transplantation in rats. Transplantation Proceedings. 2005 Jan-Feb;37(1):217-219.
L. Cicalese, M. Brown, P. Sileri, S. Morini, C. Rastellini, E. Benedetti. Pyruvate inhibits functional changes following intestinal ischemia-reperfusion injury. Surgical Forum. 2002.
M. Brown, M. Braun, P. Mercado, L. Cicalese, E. Benedetti, C. Rastellini. Pyruvate improves pancreatic islet engraftment and functionality. Transplantation Proceedings. 2001 Nov-Dec;33(7-8):3523.
C. Rastellini, X. Li, M. Braun, M. Brown, L. Cicalese, E. Benedetti. Immunosuppression through blockade of transferrin receptor: mechanisms. Transplantation Proceedings. 2001 Nov-Dec;33(7-8):3279.
L. Cicalese, C. Baum, M. Brown, P. Sileri, D. Smith, H. Abcarian, E. Benedetti. Segmental small bowel transplant from adult living-related donors. Transplantation Proceedings. 2001 Feb-Mar;33(1-2):1553.
P. Sileri, M. Brown, S. Morini, C. Rastellini, E. Benedetti, L. Cicalese. Pyruvate prevents intestinal functional changes following ischemia-reperfusion injury. Transplantation Proceedings. 2001 Feb-Mar;33(1-2):852.
C. Rastellini, M. Braun, X. Li, J. Blanchard, S. Milewski, M. Brown, L. Cicalese, E. Benedetti. Prolongation of pancreatic islet graft survival by blocking of transferrin receptor (CD71). Transplantation Proceedings. 2001 Feb-Mar;33(1-2):518-519.
E. Benedetti, C. Baum, L. Cicalese, M. Brown, V. Raofi, M. Massad, H. Abcarian. Progressive functional adaptation of segmental bowel graft from living related donor. Transplantation. 2001 Feb 27;71(4):569-571.
M. Brown, W. S. Helton. Pre- and postoperative nutrition in hepatobiliary surgery. Blumgart & Fong: Surgery of the Liver and Biliary Tract, 3/ed., pp. 531-544, 2000.
E. Benedetti, C. Baum, V. Raofi, M. Brown, C. Rastellini, M. Massad, H. Abcarian, L. Cicalese. Living-related small bowel transplantation: progressive functional adaptation of the graft. Transplantation Proceedings. 2000 Sep;32(6):1209.
C.Baum, M. Brown. Low fat/high carbohydrate diets and atherogenic risk. Nutrition Reviews. 2000 May;58(5):148-151.