Our research projects aim at understanding the characteristics of the immune cell repertoire, which is responsible for the destruction of insulin-producing beta cells, and how to regulate this process.
The focus of our research is identification of the T lymphocytes relevant for the progression of type 1 diabetes and determining the phenotypic signature of these cells. We investigate autoantigen specific T cell responses in the individuals who are at risk but have not progressed to type 1 diabetes yet and in recent onset type 1 diabetes patients. In the subjects participating in the clinical trials, we study changes in the immune repertoire induced by targeted therapies. We also aim to discover new relevant determinants from the different islet cell proteins, novel phenotypic markers and pathways in autoimmunity, which will improve the sensitivity of disease prediction, monitoring and response to therapy. Furthermore, our interest is to gain deeper insight of the disease mechanisms mediated by genetic determinants associated with disease risk and protection.
Another important area of our research includes strategies to understand the pathways leading to the recurrence of autoimmunity and destruction of the transplanted pancreas or pancreatic islets in recipients with type 1 diabetes. Methodological advances such as tetramer-based assays offer an unprecedented opportunity to characterize specificity and the functional status of autoreactive T lymphocytes in the blood and in the biopsy tissues when available. These studies will provide critical information about the immunological mechanisms regulating recurrence of autoimmunity and islet destruction in the transplant patients.
Understanding the natural history of type 1 diabetes and staging the disease process requires expertise from many investigators at City of Hope. There is much needed knowledge on beta cell biology and inflammation which have been shown to modulate the micro environment in the pancreas, T cell profiling and modulatory effect of dendritic cells on the T cell response. Our new team in the Department of Diabetes Immunology has expertise in the post-translational modifications of islet autoantigens and examining the role of beta cell stress in the generation of de novo epitopes that can break the tolerance. City of Hope also has widely recognized excellence in beta cell transplantation, as well as strong core facilities including of bioinformatics and deep-sequencing, which allows in-depth profiling of the cells of interest. All these components are essential in the assembly of the complex picture of the mechanistic pathways playing a role in the pathogenesis of type 1 diabetes.