Our laboratory is a molecular biology and immunology lab which studies innate immune sensors and receptors and their roles in infection, cancer and inflammation. Our group first described the human NLR gene family to include a few known and sixteen new genes. We have shown that these proteins play important regulatory roles during viral and bacterial infection. Among these, there are several new genes including NLRC3, NLRX1 and NLRP12 studied in this grant application. We studied the divergent roles of this family and have uncovered their roles in transcriptional activation, cytokine processing, cell death and autophagy. We were one of the first groups to show the unexpected finding that NLRP3, ASC and caspase 1/11 protected against an AOM-DSS model of colitis-associated colon cancer. We also showed that these same players can active an inflammatory response to a high fat diet, specifically in response to saturated fatty acid. In addition to the inflammasome NLRs, we have published numerous papers documenting that several NLRs regulate gene expression including class I and II MHC genes. Furthermore, a group of NLRs referred to as “regulatory NLRs” or “inhibitory NLRs”, serve as negative regulators of cell signaling pathways such as NFkB, MAPK and STAT. Interestingly these proteins play a tumor suppressor role by keeping in check a signaling threshold, thus preventing pro-survival and proliferative signals associated with cancer transformation. With translational and clinical relevance in mind, we have published several papers indicating that while expression of the inflammasome NLRs is enhanced in human colorectal colon cancer samples, the expression of regulatory NLRs are decreased in these same samples which is consistent with their negative regulatory functions. I have extensive training experience, having trained over 60 postdoctoral fellows, physician scientists and 35 pre-doctoral students.