Li Zhang M.D. Ph.D. Assistant Professor
I am motivated to find a cure for Type 1 Diabetes, an autoimmune disease. Over the last decade, I have made milestones in understanding the pathogenesis of T1D and exploring an effective immune intervention to halt or postpone the development of the disease in spontaneous diabetic mouse model and humans. Firstly, we found the disease-causing insulin autoantigen is different with the hormone insulin. It is an insulin peptide presented by the MHC class II molecule, we name it insulin register # 3 epitope. Using mouse models, we have developed different immune approached to reprogram the T1D. 1). Using the insulin register #3 protein to vaccine young mice, we were able to protected part of the treated mice from disease. 2) We generated a monoclonal antibody specific for the insulin-register #3 protein, such an antibody prevented disease. We are producing more antibodies having better binding affinity and specificity to gain higher disease protection. 3) The insulin register 3 specific antibody is a valuable tool to generate antigen specific T cells. We have generated the antibody redirected chimeric antigen receptor T cells, (CAR-T). The antigen specific CAR-CD8 T cells successfully postpone the onset of T1D following only one dose of CAR-T treatment. We are working on a CAR-regulatory T cell project which is expected to prevent and reverse diabetes.
Our final goal is to translate the animal study to human T1D studies. Human insulin register 3 is different with it is in mice. But insulin register 3 specific effector T cells are only seen in T1D patients. We already developed an antibody library and identified multiple human insulin register 3 specific antibodies. Such a group of antibodies are expected to inhibit human islet autoimmune responses by themselves, and more advanced immune therapies are expected to be created using these antibodies.