The projects in this group are from three nationally/internationally renowned institutions for type 1 diabetes (IDDM) research: the Diabetes Center of Excellence at the University of Florida, the Diabetes Research Institute at the University of Miami and the Barbara Davies Center for Childhood Diabetes. These three centers receive over $15 million of yearly research funding for type 1 diabetes. Fifteen investigators from these centers will participate in the proposed NIDDK Biotechnology center. IDDM results from poorly defined interactions between susceptibility genes, the environment, and the immune system. Studies from our institutions have shown that individuals (both relatives and the general population) at risk for IDDM can be identified by combinations of metabolic (first phase insulin response) and immunologic (autoantibodies against islet-cell antigens) markers. It has also been shown that a large number of susceptibility genes are implicated in IDDM. These susceptibility genes are probably required risk factors for the vast majority of IDDM patients; however, many genetically predisposed subjects may not develop autoantibodies or clinical diabetes. The progression from genetic predisposition to ?-cell autoimmunity is a critical, but poorly understood process. We hypothesize that the initiation of the autoimmune cascade and the resultant molecular and cellular changes culminating in clinical disease occur in genetically susceptible individuals in the very early years of life. The research programs are designed to identify genes/proteins involved in the immunopathogenesis, to discover molecular markers for disease prediction and drug targets, to understand the molecular mechanisms for disease protection by antigen-based therapies. Parallel studies will be conducted in the nonobese diabetic (NOD) mouse model and human subjects
 

The following projects are in progress:

Identification of genes involved in the pathogenesis and predictive markers for type 1 diabetes in NOD mice

Immunopathogenesis, mechanisms of prevention and surrogate endpoints in NOD mice

Molecular classification, prediction markers and surrogate endpoints for human type 1 diabetes

Gene expression profiling of in vitro-generated pancreatic islet cells