XinmingCaiXinming Cai, PhD
(Co-Mentor: Henry Haiser, PhD)

Chemical Biology & Therapeutics
Cambridge, Massachusetts, United States

Our innate immune system detects the gut microbiota by recognition of microbial-associated molecular patterns, which play a critical role in gut homeostasis and immunosurveillance. The dysregulation of gut innate immune signaling may lead to a number of inflammatory/metabolic diseases, such as inflammatory bowel disease and non-alcoholic steatohepatitis. Therefore it is critical to understand the interplay between gut microbiota and the host intestinal immune system. While the molecular mechanisms of pathogen-initiated innate immune signaling in classical immune cells such as blood-derived macrophages and dendritic cells are well established, the signaling mechanisms between the gut commensal bacteria and intestinal-associated professional and non-professional innate immune cells remain to be elucidated.

We are currently addressing these outstanding questions in intestinal innate immune signaling: 1) What are the small molecule metabolites derived from commensal bacteria that modulate the innate immune pathway and control intestinal homeostasis? 2) What intestinal innate immune sensors play critical roles in the recognition of gut bacteria? To address these questions, we use cutting-edge cell biology, immunology, and microbiology techniques in combination with state-of-the-art genetic and chemical high-throughput screening platforms. We believe these studies will expand our knowledge of intestinal innate immune regulation and potentially lead to new therapies for gut dysbiosis-associated diseases.

Selected Publications

PIKfyve, a class III lipid kinase, is required for TLR-induced type I IFN production via modulation of ATF3. 
Cai X, Xu Y, Kim YM, Loureiro J, Huang Q.
J Immunol. 2014 Apr 1;192(7):3383-9.

PIKfyve, a class III PI kinase, is the target of the small molecular IL-12/IL-23 inhibitor apilimod and a player in Toll-like receptor signaling.
Cai X, Xu Y, Cheung AK, Tomlinson RC, Alcázar-Román A, Murphy L, Billich A, Zhang B, Feng Y, Klumpp M, Rondeau JM, Fazal AN, Wilson CJ, Myer V, Joberty G, Bouwmeester T, Labow MA, Finan PM, Porter JA, Ploegh HL, Baird D, De Camilli P, Tallarico JA, Huang Q.
Chem Biol. 2013 Jul 25;20(7):912-21.

Structural basis for the autoinhibition of focal adhesion kinase. 
Lietha D, Cai X, Ceccarelli DF, Li Y, Schaller MD, Eck MJ.
Cell. 2007 Jun 15;129(6):1177-87.

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