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Chen, Jing, PhD

University of Florida, Gainesville, Florida

Project Title:

Role of T Cell Mitochondrial Function in the Pathogenesis of Type 1 Diabetes

Grant Number:

7-12-IN-09

Type of Grant:

Innovation

General Research Subject:

Type 1 Diabetes

Project Start Date:

Jul 1, 2012

Project End Date:

Jun 30, 2014

Focus:

Immunology, Other

Research Description



T cells represent a component of the immune system that function to direct immune responses against infectious agents including viruses and bacteria. Once activated, these cells help direct the immune response to clear infections. Occasionally, T cells will recognize and mount immune responses toward self-antigens, a condition known as autoimmunity. When autoimmune responses are mounted toward the body's insulin-producing beta cells, the body can no longer control blood glucose levels, and Type 1 Diabetes (T1D) occurs. A major goal in T1D research is to find ways to prevent these autoreactive T cells from attacking beta cells. One possible way is by controlling cell metabolism through the manipulation of T cell mitochondria. These important organelles provide energy, regulate cell survival, and participate in the control of cellular functions. Recent studies using animal models have revealed clues as to how mitochondria in T cells affect activation and function. Additionally, defects in T cell mitochondria have been observed in other autoimmune conditions, indicating mitochondrial dysfunction may represent an important and conserved defect leading to autoimmune disease. Little is currently known regarding the role of T cell mitochondrial function in T1D. This study seeks to determine how mitochondria in T cells of T1D patients function compared to those from non-diabetic T cells, and further, to determine how mitochondrial dysfunction impacts T cell activity. In doing so, we expect to identify new ways to predict T1D, and further provide therapeutic avenues targeting T cell mitochondrial function that will prevent the autoimmune attack on beta cells.

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?
My project covers an important part of the mechanism how Type 1 Diabetes (T1D) occurs. T-cells represent a component of the immune system that function to direct immune responses against infectious agents including viruses and bacteria. Once activated, these cells help direct the immune response to clear infections. Occasionally, T-cells will recognize and mount immune responses toward self-antigens, an abnormal condition known as autoimmunity. When autoimmune responses are mounted toward the body's insulin-producing beta cells, the body can no longer control blood glucose levels, and T1D occurs. By studying the metabolism of T cells, especially the function of T cell mitochondria, which are important organelles provide energy, regulate cell survival, and participate in the control of cellular functions, we are trying to understand how metabolic changes control T cell functions. This study seeks to determine how mitochondria in the T-cells of T1D patients function compared to those from non-diabetic T-cells, and further, to determine and how mitochondrial dysfunction impacts T cell activity. In doing so, we expect to identify new ways to predict T1D, and further provide therapeutic avenues targeting T cell mitochondrial function that will prevent the autoimmune attack on beta cells.

If a person with diabetes were to ask you how your project will help them in the future, how would you respond?
My project will focus on metabolic changes in autoimmune T cells of T1D. By completing the proposed research, we expect to identify new ways to predict T1D, these predicting methods should be reliable, easy to operate, and bring minimal stress to the individual being tested (usually children). We also expect to provide targets for development of new and effective treatment for T1D.

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 working on diabetes since graduated from medical school. A 3-year clinical experience allowed me to see how diabetes patients are suffering and in need of help. I am eager to help them. Switching from a clinician to a scientist, I am able to focus in depth on mechanisms of the disease, and try to discover new ways of therapy, prediction and prevention. This award allows me to explore an unprecedented area in T1D research, to test my hypothesis that mitochondrial and metabolic control of T cells affect their function and may contribute to immune dysregulation, which leads to autoimmunity. The proposed research will provide new knowledge of how T cell activating is metabolically controlled, and the relationship between metabolic changes and autoimmunity. These knowledge will support future studies by changing metabolism, such as alternate mitochondrial substrate utilization, to change immune system toward regulation. This will give me a good opportunity to combine my expertise in mitochondrial biology and immunology, to start a brand new area in T1D research.

In what direction do you see the future of diabetes research going?
There is currently no cure for Type 1 Diabetes. Due to lack of good biomarkers for prediction and evaluation of treatment/prevention, there is no effective preventative regimen. The ultimate goal of diabetes research is to cure the disease. For Type 1 Diabetes, switch from autoimmunity toward immune regulation will be a main task. To this end, exploration of changes of autoimmune T cells at metabolic level, molecular signaling level and gene level will help understand the mechanisms of pathogenesis and identify treatment targets. On the other hand, the target in T1D pathogenesis, pancreatic beta cells, also contributes to different degrees of susceptibility to autoimmune attacks. Therefore, to identify genes and metabolic pathways that lead to protection at beta cell level is also a direction in T1D research.