Director: Gerald T. Nepom, MD, PhD
The Benaroya Research Institute at Virginia Mason (BRI) is dedicated to research on the causes and cures of human autoimmune diseases, with a major institutional focus on type 1 diabetes (T1D). This alignment of institutional mission with the JDRF mission has created a very productive partnership, called the JDRF-BRI Center for Translational Research. Scientific goals for the Center include:
- Identify the consequences of genotypic and phenotypic variation within T and B cell populations associated with progression toward or protection from type 1 diabetes (T1D);
- Monitor and modulate this variation in the context of clinical trials designed to prevent or intervene in the progression of T1D;
- Link concepts from the T1D research community to the clinical and immunologic outcomes in our well characterized and accessible human subject populations and serve as a resource center.
In our JDRF-BRI Center for Translational Research, data and samples have been obtained on nearly 1,300 unique subjects with diabetes or relatives of individuals with diabetes, and information is maintained in our diabetes translational research database (Core A). We also have data on several hundred healthy control subjects with neither personal nor family history of any autoimmune disease, which has proven essential, e.g., in understanding the role of PTPN22 (Projects 1 and 2). Our external research base, which improved during the previous granting period, consists of human T1D research projects and clinical trials that are conducted and funded elsewhere but use our center’s core resources.
Description of Project
The four major projects are designed as translational research initiatives, focused on effector memory T cells (Project 1), B cells (Project 2), regulatory T cells (Project 3), and DQ tetramers (Project 4). In each case, the objective is to identify biomarkers and targets for the different elements of the adaptive immune system that together shape autoimmune activation and progression in T1D. Our experimental approach in each case links genotypic variation with specific phenotypic traits of disease toward interpreting the immunologic mechanism in terms of cell population, signaling, and lineage maturation. Study subjects represent a broad range of experimental immunotherapy trials and clinical outcomes. This tight linkage between basic immunobiology and in vivo clinical immunology focuses our studies on cellular mechanisms with translational and therapeutic potential.
Better understanding of the roles of T and B cells in T1D pathogenesis and the linkage of genotype and phenotype in autoimmunity Development of candidate biomarkers for disease-relevant phenotypes in T1D.
Relevance to Type 1 Diabetes
All studies in this funded Center will focus on type 1 diabetes. The raison d’être of the JDRF-BRI Center for Translational Research is to optimize the bench-to-clinic effectiveness and application of research knowledge for patients with type 1 diabetes.
Project 1: Modulation of autoreactive CD4+ T cells in T1D
Project 2: Defects in the function and requlation of the B cell compartment in T1D
Project 3: Maturation, persistence. and function of requlatorv T cells in T1D
Project 4: Generation of DQ tetramers
Core A: Clinical and translational core
Core C: Genotyping core
Core D: Administrative and enrichment core