I am currently the lead researcher for three projects In Dr. Todd Brusko’s laboratory. The first is to elucidate the functional impact of the autoimmune susceptibility variant of PTPN22 in the context of human T cells. PTPN22 is a gene that encodes a T cell receptor (TCR) signal modulating protein. TCR signal strength is critical for proper development and function of both effector and regulatory T cell repertoires. Individuals who carry a common variant of this gene have an increased risk of developing autoimmune diseases, including type 1 diabetes (T1D), systemic lupus erythematosus, rheumatoid arthritis, and others. Using lentiviral vectors, we are modulating expression of PTPN22 in human T cells to discern how the autoimmune-associated variant impacts pathogenesis.
The second project involves immune metabolism. Recently, the interplay between lymphocyte function and metabolic status has become increasingly appreciated. Specific metabolic programs and energy substrates have been shown to modulate T cell activation, differentiation, and function. The implication is that T cell activity may be manipulated to elicit specific immune environments for improved self-tolerance, allograft tolerance, anti-tumor responses, and vaccine responses. I am currently using extracellular flux analyses to define the metabolic profile of human T cells, and to discover biomarkers of T1D onset or progression. These studies are also aimed at confirming findings from murine studies and at the identification and modulation of metabolic pathways to favor regulatory T cell development.
Lastly, I am working to characterize the surface phenotypes of the immune cells from individuals with T1D and other autoimmune disorders. Using six staining panels that are consistent with the Human Immunology Consortium (Nat Rev Immunol. Feb 17, 2012; 12(3): 191–200), I have optimized a workflow to facilitate the accurate and precise assessment of over 70 immunophenotypic parameters. In conjunction with data from a comprehensive genotyping array we will determine which immunophenotypes may have clinical and genetic associations, thereby qualifying as potential biomarkers. Furthermore, this work is also expected to yield novel insights relevant to basic immunology.