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 T cells in autoimmune diabetes by microbial agents

CD4 helper T cells modulate both immunity and autoimmunity. We are exploring their role in the pathogenesis and prevention of type 1 autoimmune diabetes (T1D). There is a reciprocal relationship between regulatory Treg cells, which prevent tissue inflammation and promote self-tolerance, and proinflammatory T cells involved in the disease. In vivo helper T cells appear to have greater plasticity in switching from effector to regulatory phenotype. We are investigating Treg and IL-17 producing Th17 cell subsets following islet autoantigens and mycobacterial adjuvant immunization in prevention of T1D.

 

Dendritic cell in the modulation of autoimmunity in Type I diabetes

IInduction and progression of type 1 diabetes (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 DC subset. We are exploring the potential application of Ep1.B in modulating immunity.

 

Regeneration of insulin producing islet beta cells 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 particularly the regenerating (Reg) gene family in islet beta cell regeneration in the pancreas of NOD mice to functionally reverse T1D.

 

   

 

 
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