News & Research

    Harvard Medical School, Boston, Massachusetts

Immune mechanisms underlying type-1 diabetes

General Research Subject: Type 1 Diabetes

Focus: Gene Chips and Microarrays, Immunology, Other

Type of Grant: Mentor Based Postdoctoral Fellowship

Project Start Date: July 1, 2011

Project End Date: June 30, 2015

Research Description

The research in our lab is focused on the immune mechanisms underlying the development of Type 1 diabetes. Diabetes-susceptible mice are employed as a model system, abd leads obtained in mice are then followed up in human patients. Three major sets of questions are actively being addressed at the present time, using cutting-edge genomic and immunologic approaches:
1)    The mechanisms of defective T cell tolerance induction in NOD mice and diabetes patients.
2)    A particular regulatory cell population (Treg cells) that controls autoimmune disease: how do they work, can they be improved or targeted.
3)    External and non-invasive imaging of autoimmune attack of the islets, in mice and human.

The answers to these questions will provide important information about how diabetes unfolds in NOD mice and, hopefully, by extrapolation, in human Type 1 diabetes patients. In several of these projects, leads obtained in mice are then followed up in human patients.

Research Profile

Mentor: Benoist, Christophe M.D., Ph.D. Postdoctoral Fellow: Depis, Fabien

What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?

Type-1 diabetes is associated with loss of tolerance to pancreatic β-cell self-antigens and pancreatic islet inflammation. The aim of this project is to investigate in greater detail, molecular mechanisms of immunological tolerance, the breakdown of which leads to type-1 diabetes. In particular, we want to understand the involved in the loss of immunological tolerance. This is an early event in the development of type-1 diabetes and therefore this project seeks to provide deeper insight into etiological details of the disease. The information derived from this research may assist in the design of novel diagnostic strategies, which can be used to screen individuals at early time points and prevent long-term destruction of pancreatic tissue. In addition, this research may identify novel therapeutic targets, which may circumvent pancreatic inflammation.

If a person with diabetes were to ask you how your project will help them in the future, how would you respond?

We are trying to understand the underlying mechanisms of disease development. We know that the immune system plays a central role in initiating and perpetuating the symptoms of type-1 diabetes, but the mechanisms which trigger and control these immunological responses are currently unclear. This project will help to delineate the immunological mechanisms underlying the loss of immunological tolerance that is at the foot of type-1 diabetes and hopefully identify novel and more efficient therapeutic targets.

Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts?

Diabetes affects scores of people. Personally, there is a fervent drive to use my skills as a life scientist in such a way as to positively affect the lives of many. I feel that my contribution to diabetes research, which will be supported by this award, will in some way effect a positive outcome in people suffering with this disease.

In what direction do you see the future of diabetes research going?

There may be significant advances in development of drugs, which target immunological malfunctions in type-1 diabetes. Currently treatment is symptomatic and relies heavily on replacing insulin, but does not focus on preventing pancreatic β-cell destruction. Future research may focus on deconstructing the inflammatory pathways in pancreatic islets and also investigate means to induce β-cell regeneration.

Quelling pancreatic inflammation and restoring β-cell function would decrease the dependence on exogenous insulin replacement and prevent downstream complications of the disease.