Research Description
Type 1 Diabetes (T1D) results from the targeting of insulin producing beta-cells by cells of the immune system. Although it is known that genetics play a role in risk for Type 1 Diabetes (T1D), the influence of T1D risk genes on immune cell function is largely unknown. Many therapies aimed at curing or preventing T1D focus on targeting immune cells, thus it is important for clinical efforts to know how the function of immune cells is impacted by genetics, particularly in order to design better therapeutics. One cell based therapeutic involves delivering regulatory T cells (Tregs), which serve to suppress inflammation. However, Tregs have not been effective at lessening disease pathogenesis as of yet, possibly due to T1D risk genes impairing Treg function. This proposal will use new gene editing tools (e.g., CRISPR/Cas9) in immune cells in order to investigate the role of mutations called single nucleotide polymorphisms (SNPs) that confer risk for T1D in driving T cell and Treg function. The results from this project will aid in our understanding of how individual SNPs can regulate beta-cell specific T cell and Treg function and has the potential to inform on the design and selection of cell or drug-based therapies.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 research project centers around the genetics of Type 1 Diabetes (T1D), in particular how the genes associated with risk for T1D may impact T cell function. T cells are thought to be important mediators of insulin producing beta cell destruction, as such there are many therapeutics under investigation to target these cells, one of which is the sole FDA approved therapeutic for disease delay, Teplizumab. Although multiple lines of evidence implicate T cells as being important in disease pathogenesis, little is known about what drives these cells to attack beta cells in T1D. Investigating the role of T1D genetics in promoting T cell autoimmunity may help to inform us about certain patient populations who may respond better to certain drugs based on their genetics, and may also lead to opportunities to engineer T cell therapies which can better suppress the autoimmune response.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?I hope that my project will help us to better understand what causes T cells to behave abnormally in T1D, and therefore help us to better target these cells to reduce their potential to cause or exacerbate disease. It will be critical to understand the influence that genetics has on T cell function in order to design optimal clinical trials based on patient genetics, as well as optimized therapeutics that counteract the influence of these genes on immune cells.
Why important for you, personally, to become involved in diabetes research? What role will this award play?I have a personal connection to T1D in the form of my sister, whose diagnosis inspired my interest in research. Personally witnessing the struggles that accompany this disease has pushed me towards an interest in projects with a translational focus. I hope to make basic science advances that have clinical implications, such as improvements in engineered adoptive cell therapy or precision medicine therapeutics. This award will be critical for beginning my trajectory towards an independent research career and establishing my own interests and expertise in the field.
In what direction do you see the future of diabetes research going?I see the future of diabetes research involving increased collaboration between the fields of engineering/computational science and biomedical science. As an aspiring interdisciplinary researcher, I believe that it will be extremely important to integrate multiple data modalities/techniques and diverse perspectives in order to obtain a comprehensive view of T1D pathogenesis. I envision collaborations between these fields vastly improving disease modeling and curative efforts alike.