Research Faculty

Klaus Pechhold, MD, Associate Professor

Diabetes Mellitus is a disease of largely unknown etiology characterized by an inadequate supply and/or function of insulin. The hormone insulin is secreted by highly specialized cells in the pancreas. These beta cells, together with other endocrine cells, form scattered cell clusters histologically known as pancreatic islets. They control fluxes of nutrients, maintaining constant blood glucose levels by integrating intestinal supply from food and internal reservoirs during fasting. Our laboratory is interested in characterizing gene regulation as it pertains to the homeostasis of islet beta cells, focusing our efforts on transcriptional alterations in islet cells during metabolic challenges and disease diabetes development. In particular, we hope to identify therapeutic targets for regenerative medicine. This is a realistic goal because it is well known that, at least in rodents, pancreatic islets’ beta cell content can increase and/or its function improve not only prenatally, but also during rapid growth in adolescence, and pregnancy, the same mechanisms that could serve to avoid, offset or delay diabetes development. Methodologically, our laboratory applies a recently established approach to examine islet cell mRNA and microRNA gene expression patterns with unprecedented sensitivity and precision. It is accomplished by applying quantitative nuclease protection array technology (qNPA) on fluorescence-activated cell sorter (FACS) purified islet cell subpopulations.”

Sally Kent, PhD, Assistant Professor

My research focus is on three areas of the autoimmune response in type 1 diabetes (T1D). First, I will ask if there evidence of autoantigenic driven oligoclonal expansion of T cells in difficult-to-obtain pancreatic draining lymph nodes of T1D subjects and what are the autoantigenic epitopes recognized by the expanded T cells. Second, the role of autoreactive B cells in antigen recognition, costimulation, and cytokines secretion in the autoimmune response is not known in the development of T1D in humans. We propose to study, on a single cell basis PLN B cells from T1D subjects bearing functional markers for reactivity with cognate self-target(s) by the newly developed micro-engraving technology. Single cell isolated autoantigen reactive B cells identified by this technology will be sequenced for B cell receptor clonal expansion, isotype switching, and somatic mutation as hallmarks of antigen driven clonal expansion. Third, I will examine the development from a naïve to a memory T cell phenotype of autoantigen-reactive T cells in the periphery of T1D subjects. We know that specific autoantibodies are detected in sera of individuals at risk for developing T1D, prior to disease onset. I will ask when are memory autoantigen reactive T cells detected in the periphery of at-risk individuals and if this phenotype switch is linked to specific autoantibody detection.