Research Description
Autoimmune type 1 diabetes (T1D) is a heterogenous disease, but the basis of this variation is not fully understood. T cells of the immune system participate in the destruction of insulin producing islets in the pancreas, and some T1D subjects have increased levels of a subtype of T cells, Tscm cells, that can regenerate and replenish destructive T cells. Thus, Tscm cells may be a reservoir of destructive T cells in T1D. This proposal will test whether Tscm cells contribute to variation in disease progression and response to treatment in people before and after T1D diagnosis. Existing patient cohorts and data will be used to 1) determine whether Tscm cells before diagnosis correlate with development T1D; 2) test if Tscm cell levels correlate with loss of insulin production in T1D subjects; 3) assess whether genetic risk or age of disease onset is associated with increased levels of Tscm cells in subjects at risk to develop diabetes or after T1D diagnosis; and 4) determine if T1D subjects with increased Tscm cells have a worse response to drugs in clinical trials to prevent or reverse T1D. The significance of this study to T1D is two-fold: the results will contribute to understanding the biology underlying T1D disease heterogeneity which is essential for accurately predicting disease progression and stratifying patients for appropriate treatment. Further, the results will lay the groundwork for future studies of Tscm cells as markers in development of precision medicine approaches to T1D.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 study will address disease heterogeneity in patients with type 1 diabetes (T1D) by studying a recently identified population of T cells with stem-like properties that are expanded in a subset of T1D patients to determine their relationship to the disease process. The results will provide valuable knowledge on mechanisms underlying disease heterogeneity which is essential for accurately predicting disease progression, stratifying patients for appropriate treatment, and determining appropriate timing of therapy. The results will be immediately translational in natural history studies and clinical trials and applicable to the development of precision medicine approaches to T1D.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?The purpose of this study is to link a unique immune cell type to variability in T1D disease progression and response to immunotherapy. The significance of the results of this study to T1D is to improve our understanding of the biology underlying T1D disease variation, which is essential for accurately predicting disease progression, stratifying patients for appropriate treatment, and determining the best time to treat patients to prevent and cure T1D. The results will be immediately applicable in clinical studies and drug trials in T1D and to the development of precision medicine approaches to T1D.
Why important for you, personally, to become involved in diabetes research? What role will this award play?I am passionate about research in T1D because it is the only autoimmune disease which does not have an FDA approved drug for treatment or prevention of disease. T1D has a clear link to the immune system and understanding why some individuals get T1D, how fast disease progresses and what drugs will best treat each subject is essential to improving the lives of people at risk for and living with T1D. This award will allow our group to expand our study of T cells with stem-like properties in T1D by linking these cells to disease using data from unique cohorts of patients participating in clinical studies of disease progression and immunotherapy trials.
In what direction do you see the future of diabetes research going?The T1D field is on the cusp of breakthroughs in preventing and delaying disease in individuals who are at risk for T1D. There are also new therapeutic approaches in both the at risk and new onset T1D populations that will more specifically target the immune cells involved in beta cell destruction rather than drugs that mediate global immunosuppression. Linking immune intervention with treatments targeting beta cell health are likely to be the most successful in preventing and treating T1D.