Immunobiology of type 1 diabetes

General Research Subject: Type 1 Diabetes

Focus: Immunology, Islet Biology, Transplantation

Type of Grant: Mentor Based Postdoctoral Fellowship

Project Start Date: July 1, 2006

Project End Date: June 30, 2010

Research Description

Research in the Haskins lab is focused on understanding the autoimmune basis of type 1 diabetes using the NOD mouse model and a panel of well-defined, autoreactive T cell clones made from the NOD mouse that can rapidly induce full-blown diabetes when transferred to young mice. These T cell clones are thus defined as diabetogenic. The goal of these studies is to understand better the immunological mechanisms by which autoreactive T cells contribute to the diabetic disease process. One project is to determine which molecules made by diabetogenic T cells are necessary to their disease-inducing properties. A second project focuses on one particular T cell signaling molecule called CD40 that appears to be more highly expressed on T cells in autoimmune animals and may be a marker of pathogenicity. A third project is aimed at determining the autoantigens in the beta cell that are targeted by autoreactive T cells. A fourth project is aimed at deriving regulatory T cells, a type of T cell that suppresses the activity of diabetogenic T cells and thus may play an important role in prevention of disease. A better understanding of how diabetogenic T cells work and how they may be inhibited by other types of T cells is important to the development of new strategies for therapy in human patients.

Reseacher Profile

Mentor: Kathryn Haskins, PhD  Postdoctoral Fellow:  Rocky L Baker, MD

What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes? My project is in the area of Immunology and focuses on the role of the CD40 molecule on pathogenic T cells that induce type 1 diabetes (T1D) in the NOD mouse model. One implication of this project could bear on prevention of diabetes as the marker we are investigating could potentially be used to detect autoreactive T cells. In addition, the CD40 molecule on T cells could have implications for new immunotherapeutic strategies.

If a person with diabetes were to ask you how your project will help them in the future, how would you respond? My project aims to identify and target autoreactive T cells that are involved in the pathogenesis of T1D. If asked how my project will help patients, I would respond that a better understanding of the molecules on these T cells could lead to better methods for diagnosis and protection or treatment. In addition to finding ways to improve islet transplantation, we also need to understand how to stop the autoimmunity.

Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts? I have worked in the biomedical field for more than 5 years, mostly in clinical labs as a resident. Part of the work included diagnosis and follow-up of diabetes patients. Being able to participate in diabetes research will enable me to play an active role in the biomedical field with an understanding of both the clinical aspects and the research side of this disease. On one hand, the clinical background makes it easier for me to collaborate and discuss issues with clinicians, and on the other hand, my postdoctoral research experience may, for example, help me to identify the shortcomings of currently available diagnostic tests and try to adjust the strategy. Overall, this research award will help me to attain my goals to be able to interface between the clinical world and the research world.

In what direction do you see the future of diabetes research going? I am convinced that early stage diagnosis is key to preventing type 1 diabetes. A big step in diabetes research will be to identify in a reproducible manner specific cell populations that are responsible for causing the disease. Ultimately, specific therapeutic strategies to eliminate autoreactive cells in a precise and targeted way will help lead to a cure for T1D.