News & Research

    University of Tennessee Health Science Center, Memphis, Tennessee

Genetic control of CD4 T-cell gene expression abnormalities in young NOD mice

General Research Subject: Type 1 Diabetes

Focus: Gene Chips and Microarrays, Genetics\Type 1 Diabetes, Immunology

Type of Grant: Basic Science

Project Start Date: July 1, 2011

Project End Date: June 30, 2014

Research Description

Type 1 diabetes (T1D) is due to the destruction of insulin producing cells in the islets of Langerhans by the immune system. It is not known why the immune system 'fails' and begins to destroy this tissue. The body has a large reserve of islets and it is only after 90% of the insulin producing cells have been destroyed that clinical symptoms of the disease (high blood glucose) are detected. If the factors involved in the early stages of T1D development, prior to islet destruction, could be defined then it may become possible to stop the process before clinical disease with all its severe complications occurs. To discover these factors, we evaluate the gene expression in circulating white blood cells of a mouse strain (NOD) that is highly susceptible to developing T1D. These mice develop diabetes after 12 weeks of age. We compare gene expression in diabetes prone NOD mice at 2-4 weeks of age to gene expression in normal (diabetes-resistant) mice to find genes that are uniquely expressed during the early stages of T1D development. We have discovered many such genes in a specific white blood cell called the CD4 T-lymphocyte. In the proposed work, we would like to identify the regions in the chromosomes that are responsible for causing these genes to be expressed differently in the NOD mice. These discoveries would lead to new understandings of how T1D occurs and could open up new avenues to diagnose and treat individuals before an actual disease develops.

Research Profile

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

This project is focused on type 1 diabetes and in particular trying to understand the genetic regulation of the immune system failures that are the basic for development of these autoimmune diseases.  Genetic studies have suggested that specific genes are giving individuals an increased susceptibility to develop type 1 diabetes.  Other studies including some from our group have suggested that the early stages where the disease is initiated are associated with abnormal expression of specific groups of genes.  This project is attempting to connect individual gene expression abnormalities to specific genes that control those abnormalities. 

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

The understanding of how specific gene expression abnormalities in type 1 diabetes is connected to specific genes regulating each abnormality should allow us to develop better ways to intervene and correct those abnormalities.  This may allow a much better type of intervention that is targeted to each individual and his/her specific immune system failures.

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 been doing diabetes research for my whole career as a scientist (over 25 years).  I have both family and friends that have suffered from this disease.  As an immunologist I have been intrigued by the phenomena that a process such as an immune response, that normally serve good purposes (of defending against infections), can somehow be subverted and cause damage to the body.  My laboratory was facing the loss of NIH funding and was getting ready to downsize when the news of this award came.  This award will allow me to keep a team of highly trained professionals together and continue a very important research effort.

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

It is my hope that we eventually will be able to understand the details of how genes and environment interact with each other to cause diabetes.  This would allow us to define an individual’s risk of developing the disease and intervene before the preclinical abnormalities develop into actual disease.  By understanding how each gene affect specific gene expressions we could look for these early molecular abnormalities and individualize interventions for each person depending on his/her genes as well as gene expression profiles.