Director: Diane Mathis


The major goals of the JDRF Center on Immunological Tolerance in Type-1 Diabetes at Harvard Medical School are to identify mechanisms responsible for the defective T cell tolerance at the root of type-1 diabetes, and to exploit this knowledge to develop novel strategies for preventing or reversing the disease. The essence of the renewed Center will be a JDRF-funded confederation of 8 research Projects, 2 technological Cores and an Administrative Core. A cluster of three Projects will develop novel murine:human chimeric systems, and then exploit them to study the breaking and remaking of T cell tolerance in T1D patients. A second cluster of four Projects will focus on new molecular and cellular immonoregulatory agents, how they translate to the human context, and how they can be harnessed to therapeutic ends. The eighth Project will explore the relationship between autoimmunity and inflammation in NOD diabetes, and will test the therapeutic efficacy of anti-inflammatory reagents in halting disease. The technological Cores will provide access to state-of-the-art mouse and murine:human models, and to clinically, immunologically and genetically characterized T1D patient and control blood samples. The Center can also draw on a number of allied resources at the Joslin Diabetes Center and within the Harvard Community more generally, which greatly enriches its scientific base and potential.

Relevance to Type 1 Diabetes

The Center is focused on learning to re-establish immunological tolerance, which is central to prevention and therapy of Type 1 Diabetes.

Project 1: Defective central tolerance induction in humans?

Project 2: Autoreactive humanized TCR transgenic mice in T1D

Project 3: Regulation and homeostasis of diabetic human T cells

Project 4: Genomics of FoxP3+ Treg cells in mice and humans
Project 5: Dissecting TGF- signaling during differentiation of effector and regulatory T cells

Project 6: Pathogenic and Regulatory T Cells in Type 1 Diabetes

Project 7: Induction of beta cell specific regulatory T cells

Project 8: The autoimmunity/inflammation connection in type-1 diabetes

Core A: Manipulated NOD Mouse Core

Core C: Human Sample Procurement Core

Core D: Administrative Core