Autoimmunity; Cell growth, differentiation and development; Gene Expression; Immunology; Molecular and Cellular Biology; Molecular genetics; Signal Transduction; Transcription and Translation; Transgenic organisms
As a faculty member at the University of Buffalo, I have studied the signaling pathways and transcriptional networks that regulate the differentiation of immune cells such as B and T lymphocytes and how they are impaired in autoimmune diseases. These studies have been funded both by the NIH and by private foundations including the Lupus Research Institute, the Alliance for Lupus Research, the International Myeloma Foundation and the American Cancer Society. I have been particularly interested in identifying the roles of the transcription factor Ets1 in B cell differentiation and B cell tolerance to self-antigens. Mice lacking Ets1 develop an autoimmune disease with similarities to human lupus and the human Ets1 gene has been identified as a susceptibility locus for a number of different human autoimmune diseases. To mechanistically understand how Ets1 regulates immune cell function and prevents development of autoimmune disease, my lab has extensively investigated the phenotypes of mice lacking Ets1 either globally or in B cells to identify pathways and target genes that are important in the autoimmune phenotype. My lab has also been interested in signaling pathways that regulate the expression and activity of immune cells, including the BCR signaling pathway, Toll-like receptor pathways, the CD22/SHP1 inhibitory pathway and the Notch pathway. Recently, we've developed an interest in the B cell co-receptor signaling pathway involving CD19/CD21 binding to C3d deposited on the surface of pathogens. We also have an interest in understanding how Ets1 cooperates with IL17RA signaling to regulate skin immune responses to bacterial infection.