Autoimmune diseases are complex disorders, with both environmental and genetic components. Recent genome wide association studies have identified a large number of genetic variants that contribute susceptibility to autoimmunity. The vast majority of these variants fall in genes that function in the immune system, underscoring the importance of immune dysfunction in disease initiation and progression. Research is now focused on determining the functional consequences of autoimmune genetic variants.
We are interested in elucidating the impact of autoimmune genetic variants in T and B cell signaling pathways on the breakdown in immune tolerance in autoimmunity. Our research utilizes cellular and molecular assays of immune cells isolated from genotyped healthy controls and autoimmune research participants to identify the mechanism of action of genetic variants and the cellular consequences. Current work is focused on genetic variants in the PTPN2, IL2RA, BANK1, BLK, STAT3, JAK2, TYK2, IL6R, IFIH1, and SH2B3 genes in several autoimmune disorders.
The lab is also analyzing the T cell receptor repertoire in peripheral T cells in people with type 1 diabetes using next generation sequencing, with the goal of identifying T cell receptor ‘signatures’ that may be useful biomarkers for disease initiation and progression.
This work will provide insight into the genetic mechanisms underlying autoimmunity and has the potential to identify new biomarkers of disease and therapeutic targets for intervention.