The study of microbial communities that reside on and within the human body (the microbiome) is considered one of the hottest areas of science today. It is now well appreciated that the microbiome has remarkable influence on diverse aspects of human health and disease. To understand how the microbiome exerts such influence, our lab seeks to define the mechanisms by which cells of the immune system interact with microbes that reside in the intestine. To the immune system, co-existence with microbes is a remarkable paradox: while immune cells are skilled operatives fixated on eliminating microbial invaders, these same cells are somehow restrained from attacking microbial commensals. This restraint is critical to prevent inflammatory bowel disease (IBD).
Our research seeks to understand the pathogenesis of inflammatory bowel disease, and understand interactions between host and the microbiome. In particular, we study the roles of dendritic cells. Dendritic cells are exquisitely sensitive to microbes, and after engaging microbes or microbial products, dendritic cells are reprogrammed into inflammatory cells with potent ability to activate other immune cells. Because of their potent influence over the immune system, dendritic cells are in a prime position to relay signals from the microbiome, and we have found that dendritic cells are key players in pathogenesis of inflammatory bowel disease. To prevent IBD, dendritic cells require the NF-kB suppressor, A20. A20 suppresses multiple disease-associated signaling pathways, including TNF, NOD2 and Toll-like receptors. Using biochemistry and in vivo analyses, we are interrogating the roles of these receptors and signaling pathways in regulating the responses of dendritic cells to the intestinal microbiome. Additionally, we seek to identify new signaling pathways by which DCs interact with microbial communities of the intestine.
Education and Training
- University of California at Berkeley, Ph.D. 2006
Selected Grants and Awards
- Role of osteopontin in innate immunity during infections and inflammation
- Duke Training Grant in Digestive Diseases and Nutrition
- Identification of anti-commensal T cells, their pathological function, and their commensal antigen specificities in inflammatory bowel disease using a novel in vivo reporter system
- Role of Dendritic Cell-mediated T Cell Activation in Salt-sensitive Hypertension
- Dendritic cells in colorectal cancer
- IL-27 in skin host defense and regeneration
- Basic Immunology Training Program
- Microbiota induced upregulation of PDL1 on intestinal dendritic cells in intestinal tumorig
- The role of dendritic cell-mediated T cell activation in hypertension
- Dendritic cell orchestration of colitogenic T cells in inflammatory bowel disease