My expertise is in T cell and B cell Immunity, Immunological Tolerance and Nonhuman Primates Immunology. My work primarily focuses on understanding the development of the xeno/allo immune response. My main goal is to understand the role of regulatory T and B cells in islet xenoimmunity and to identify the mechanisms critical to the induction of donor-specific regulation of xenoimmunity by Tr1 cells in concert with regulatory cells of myeloid and lymphoid origin. Our recent work, published in Nature Communication, described a novel tolerance protocol using a nonhuman primate animal model for optimal clinical translatability. We have considerably extended field knowledge by demonstrating lasting tolerance to islet allografts in monkeys undergoing immunosuppression and determined that the reduction in donor-specific T and B cell clones along with strong, unremitting regulation contributed to this tolerance. Based on the early and late immunological profiles obtained from this ongoing work, our approach is highly promising as a guide for designing improved human tolerance protocols and ultimately curing type 1 diabetes. We are firmly convinced that to better understand the immune tolerance mechanisms, it is essential that all immune system components are analyzed simultaneously and inter-relationships between these are taken into account. This has recently been made possible by improved system level immune monitoring techniques with the development of novel high-dimensional methods operating at single-cell resolution, such as Mass cytometry (CyTOF: Cytometry by Time-Of-Flight, epiTOF), Imaging Mass Cytometry (IMC) and scRNA-seq. A recent new direction of my work is the analysis of donor reactive lymphocytes turnover using a novel TCR tracking approach to understand the interplay of tolerance and cellular islet xenograft rejection. Using these cutting edge technologies, I am studying the immune phenotype of induction, maintenance and loss of tolerance.
Immunobiology of Tolerance
AddressSchulze Diabetes Institute
515 Delaware St SE
Minneapolis, MN 55455-0357