Mia Smith PhD, DVM

My laboratory studies the role of autoreactive B cells during development of type 1 diabetes (T1D), as well as other autoimmune disorders. The focus of my research is in understanding how these B cells become activated and work in concert with other cells of the immune system, such as T cells, to ultimately destroy the insulin-producing cells of the pancreas, leading to diabetes. Studies so far indicate high affinity insulin-reactive B cells are normally silenced by anergy, a state of unresponsiveness, and can be found in the peripheral blood of healthy individuals. However, in autoantibody positive and recently diagnosed individuals, these cells become activated and leave the peripheral blood.  The absence of these cells from the peripheral blood corresponds with their presence in the islets of early onset T1D subjects. Moreover, loss of anergic B cells is associated with individuals who carry high risk HLA (DR4-DQ8) and/or non-HLA T1D risk alleles (INS, PTPN2, IKZF3). My current and future research focus is further understanding the mechanisms that drive loss of B cell tolerance and the association of particular genetic risk alleles with loss of peripheral tolerance in autoimmunity. It is my goal that results from my studies will translate into possible future therapeutics to help prevent, delay, or treat type 1 diabetes.

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