Liwu Li
Associate Professor in Internal Medicine and Associate in Biochemistry

Ph.D., 1996 University of Michigan
Post Doctorate, 1999 University of Michigan

My research focuses on the signaling events controlling the innate immune response. Human monocytes produce inflammatory proteins in response to microbial stimulation. A family of Toll-like receptor proteins recognize a diverse array of microbial secretions and relay the signals through a serious of intracellular signaling components including MyD88, IRAK, and TRAF6 proteins. In particular, we are focusing on the characterization of the novel kinase IRAK. We observed the Interleukin-1 receptor-associated kinase (IRAK), a signal transducer for interleukin-1 (IL-1), also participate in the Toll-like receptor (TLR) mediated innate immune response to bacterial endotoxin lipopolysaccharide (LPS). Using the human promonocytic THP-1 cell line, we demonstrated that the endogenous IRAK is quickly activated in response to bacterial LPS stimulation. LPS also triggers the association of IRAK with MyD88, the adaptor protein linking IRAK to the TLR/IL-1b receptor intracellular domain. Macrophage cells with prolonged LPS treatment become tolerant to additional dose of LPS, and no longer express inflammatory cytokines. We observed that the quantity of IRAK is greatly reduced in LPS tolerant THP-1 cells, and its activity no longer responds to further LPS challenge. Strikingly, the IRAK homologue, IRAK2 protein does not undergo degradation upon prolonged LPS stimulation. Future studies will be focusing on the differential regulation of cellular IRAK and IRAK2 protein level and kinase activity in response to LPS challenge in leukocytes.

Recent Publications (selected):