Scott, Fraser - University of Ottawa - Department of Biochemistry, Microbiology and Immunology

研究领域

Our lab is interested in how environmental factors, particularly dietary antigens, influence the development of T1D [1,2]. A major focus is to understand the diabetes-promoting interactions between dietary antigens, the gut immune system and endocrine pancreas by (i) characterizing pathways in gut and pancreas that are abnormal [3-5] and (ii) defining abnormal gut immune responses to dietary and microbial antigens that promote or inhibit diabetes in animals and patients [6,7]. T1D is an autoimmune disease in which the patient's immune system destroys the insulin-producing β-cells in the pancreatic islets. The remarkable ~2-4 fold increase in incidence over the past 60 years is not explained by changes in genetic risk, but is thought to be due to factors in the environment. The prime suspects are enteroviruses, dietary antigens and gut microbes. All of these agents have their first major encounter with the immune system in the gut. Thus, successful treatment or prevention of diabetes depends on a better understanding of how these factors influence the gut immune system, pancreas inflammation and β-cell health (FIG.1).

近期论文

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Patrick C, Wang GS, Lefebvre DE, Crookshank JA, Sonier B, Eberhard C, Mojibian M, Kennedy C, Brooks SPJ, Kalmokoff M, Maglio M, Troncone R, Poussier P, Scott FW. Promotion of autoimmune diabetes by cereal diet in the presence or absence of microbes associated with gut immune activation, regulatory imbalance and altered cathelicidin antimicrobial peptide. Diabetes 62:2036–2047, 2013 Jörns A, Arndt T, Vilsendorf AM, Klempnauer J, Wedekind D, Hedrich HJ, Marselli L, Marchetti P, Harada N, Nakaya Y, Wang GS, Scott FW, Gysemans C, Mathieu C, Lenzen S. Islet infiltration, immune cell activation and β-cell death in the NOD mouse, BB rat, Komeda rat, and LEW.1AR1-iddm rat in comparison with the pancreas of patients with type 1 diabetes. Diabetologia, 57:512-21 2014 Mojibian M, Chakir H, Lefebvre DE, Crookshank JA, Sonier B, Keely E, Scott FW. A diabetes-specific HLA-DR restricted pro-inflammatory T cell response to wheat polypeptides in tissue transglutaminase antibody negative patients with type 1 diabetes. Diabetes 58: 17891796, 2009 (See Editorial Commentary, p. 1723) MacFarlane AJ, Strom A, Scott FW. Epigenetics – Deciphering how environmental factors may modify autoimmune Type 1 diabetes Mammalian Genome, 20:624-32, 2009 Sonier B, Patrick C, Ajjikuttira P, Scott FW Intestinal immune regulation as a potential diet-modifiable feature of gut inflammation and autoimmunity International Reviews of Immunology, 28:414-45, 2009 MacFarlane AJ, Burghardt KM, Kelly J, Simell T, Simell O, Altosaar I, Scott FW A type 1 diabetes-related protein from wheat (Triticum aestivum): cDNA clone of a wheat storage globulin, Glb1, linked to islet damage J. Biol. Chem. 278:54-63, 2003 (Cover Article) Chakir H, Wang H, Lefebvre D, Webb J, Scott FW T-bet/ Gata-3 ratio as a measure of Th1/Th2 cytokine profile in mixed cell populations: predominant role of GATA-3 J. Immunol. Methods 278: 157-169, 2003 Courtois P, Sener A, Scott FW, Malaisse WJ. Disaccharidase activity in the intestinal tract of Wistar-Furth, BBc and BBdp rats Brit. J. Nutrition 91:201-9, 2004 Valverde I, Wang GS, Burghardt KM, Kauri LM, Redondo A, Acitores A, Villanueva-PeZacarrillo ML, Courtois P, Sener A, Cancelas J, Malaisse WJ, Scott FW. Bioactive GLP-1 in gut, receptor expression in pancreas and insulin response to GLP-1 in diabetes-prone rats. Endocrine 23:77-84, 2004 Courtois P, Sener A, Scott FW, Malaisse WJ. Peroxidase activity in the intestinal tract of Wistar-Furth, BBc and BBdp rats. Diabetes Metabolism Research & Reviews 20:305-14, 2004 Nikulina M, Habich C, Flohé SB, Scott FW, Kolb H. Wheat gluten causes dendritic cell maturation and chemokine secretion. Journal of Immunology 173:1925-33, 2004 Graham S, Courtois P, Malaisse WJ, Rozing J, Scott FW, Mowat AM. Enteropathy precedes type 1 diabetes in the BB rat. Gut 53: 1437-1444, 2004 Malaisse WJ, Courtois P, Scott FW. Insulin-dependent diabetes and gut dysfunction: the BB rat model Hormone & Metabolic Research 36:585-94, 2004 Courtois P, Jurysta C, Sener A, Scott FW, Malaisse WJ. Quantitative and qualitative alterations of intestinal mucins in BioBreeding rats. Int J Mol Med. 15:105-8, 2005 Courtois P, Nsimba G, Jijakli H, Sener A, Scott FW, Malaisse WJ. Gut permeability and intestinal mucins, invertase and peroxidase in control and diabetes-prone BB rats fed either a protective or diabetogenic diet. Digestive Diseases & Sciences 50: 266-275, 2005 Wang G-S, Rosenberg L, Scott FW Tubular complexes as a source for islet neogenesis in the pancreas of diabetes-prone BB rats Laboratory Investigation 85:675-688, 2005 (Editor Commentary – Inside Lab Invest) Chakir H, Lefebvre D, Wang H, Caraher E, Scott FW Wheat protein-induced pro-inflammatory Th1 bias in gut-associated lymphoid tissues of young diabetes-prone rats Diabetologia 48:1576-84, 2005 Schmidt G, Sirois F, Anini1 Y, Kauri LM, Gyamera-Acheampong C, Fleck E, Scott FW, Chrétien M, Mbikay M Differences of pancreatic expression of 7B2 between C57BL/6J and C3H/HeJ mice and genetic polymorphisms at its locus Sgne1Diabetes 55:452-459, 2006 Mojibian M, Chakir H, MacFarlane AJ, Lefebvre DE, Webb JR, Touchie C, Karsh J, Crookshank J, Scott FW Immune Reactivity to a Glb1 Homologue in a Highly Wheat Sensitive Patient with Type 1 Diabetes and Celiac Disease Diabetes Care 29:1108-1110, 2006 Lefebvre DE, Powell KL, Strom A, Scott FW. Dietary Proteins as Environmental Modifiers of Type 1 Diabetes Mellitus Annual Review of Nutrition 26:175-202, 2006 Wang GS, Kauri LM, Scott FW The potential for dietary modification of islet ß-cell homeostasis in autoimmune diabetes. Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Immunology, Endocrine and Metabolic Agents) 7: 231-240, 2007 Strom A, Wang G-S, Reimer R, Finegood DT, Scott FW. Pronounced cytosolic aggregation of cellular prion protein in pancreatic ß-cells in response to hyperglycemia Lab Investigation 87: 139-149, 2007 (Cover) Kauri LM, Wang G-S, Patrick C, Bareggi M, Hill DJ, Scott FW. Increased islet neogenesis without increased islet mass precedes autoimmune attack in diabetes-prone rats. Laboratory Investigation 87:1240-51, 2007 Thakare K, Shi W, Barbeau WE, Bassaganya-Riera J, Hontecillas R, Scott FW Investigation of chloroform-methanol soluble wheat proteins and sphingolipids as potential dietary triggers of diabetes in BBdp rats Food and Agr Immunol 19:25-48, 2008 Simpson M, Mojibian M, Barriga K, Scott FW, Fasano A, Rewers M, Norris JM. An exploration of Glo-3A antibody levels in children at increased risk for type 1 diabetes mellitus. Pediatric Diabetes 10:563-72, 2009