Welcome to the Singh Lab

The University of Western Ontario
Schulich School of Medicine & Dentistry
Department of Microbiology & Immunology

Cellular basis for the activation of regulatory CD4+CD25+ and effector Th17 T cells in autoimmune diabetes by microbial agents

Regulatory T cells modulate both immunity and autoimmunity. We are exploring the role of these cells in the pathogenesis and prevention of type 1 diabetes (T1D). This includes induction of CD4+CD25+ (Treg) cells and Th17 effector cells. There is a reciprocal relationship between Treg cells, which prevent tissue inflammation and promote self-tolerance, and Th17 cells that are generally proinflammatory. We are investigating novel IL-17-producing T cell subsets and elucidating the role of proinflammatory cytokines following mycobacterial immunization.

Dendritic cell and Regulatory T cell mediated modulation of autoimmunity in Type I diabetes

We explore the disease prevention strategies using regulatory T cell subsets and autoantigens involved in type 1 diabetes (T1D). Induction and progression of T1D is dependent on antigen presenting cells, particularly dendritic cells (DC). Different subsets of DCs are critical for the induction and effector phase of the disease. The goal of this project is to use DCs to prevent and modulate T1D using the NOD mouse model of T1D. Further, to correlate the data from the mouse model of T1D with human subjects, we characterize and assess peripheral blood DCs from subjects with T1D. In line with our goals, our lab has discovered a novel peptide fragment of apolipoprotein E (ApoE), termed Ep1.B, which induces the differentiation of monocytes into a disease protective plasmacytoid DC subset. We are exploring the potential of Ep1.B in modulating autoimmunity.

Modulation of islet beta cell expansion in pancreatic tissue

There is considerable evidence that insulin producing beta cells in the pancreatic islets can regenerate through formation of new islet-like cell clusters containing beta cells. We previously showed diabetes prevention and islet preservation in NOD mice by treatment with mycobacterial preparations such as complete Freund’s adjuvant (CFA) or BCG. Several recent studies have confirmed regeneration of beta cells in the islets and following prevention of autoimmunity. The specific aim of our work is to investigate the expression of various transcription factors of the Reg gene family that are involved in islet beta cell regeneration in the pancreas of NOD mice, and to functionally characterize these regenerated cells.




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