Research in my lab focuses on the signaling events controlling the innate immunity, infection, and inflammation. Alteration in innate immunity has been recognized to contribute to various human diseases including cancer and atherosclerosis. A family of Toll-like receptor proteins recognize a diverse array of microbial as well as other cues and relay the signals through a serious of intracellular signaling components including the interleukin-1 receptor-associated kinase (IRAK) family proteins (1, 2, M, and 4). Each IRAK member has unique regulation and role in mediating innate immune response. In contrast to IRAK4 which plays a critical role in the canonical NFkB activation pathway, we have demonstrated that IRAK1 is critically involved in Stat activation. IRAK1 undergoes stimulus-dependent sumoylation and nuclear translocation. IRAK-M, on the other hand, negatively regulates NFkB activation.
We are also interested in the examination of other signaling molecules involved in innate immunity such as Tollip. We have found that Tollip can specifically bind with phosphatidylinositol-3-phosphate, and such binding may be essential for its cellular function.
Future studies include detailed biochemical, molecular as well as functional studies of IRAK family kinases and other signaling molecules involved in innate immunity. In particular, we plan to determine the nature of IRAK1 modification and nuclear localization as well as identifying other gene targets of IRAK1. The involvement of IRAK proteins in the pathogenesis of atherosclerosis as well as cancer will be examined using animal models.
Selected Publications:
For recent publications since 2002 click here.
Gan L, Li L. (2006) Regulations and Roles of the Interleukin-1 Receptor Associated Kinases (IRAKs) In Innate and Adaptive Immunity. Immunologic Research. 2006;35(3):295-302.
Fasciano S, Li L. (2006) Intervention of Toll-like receptor-mediated human innate immunity and inflammation by synthetic compounds and naturally occurring products. Curr Med Chem. 13(12):1389-95.
Paulsen MT, Starks AM, Derheimer FA, Hanasoge S, Li L, Dixon JE, Ljungman M. (2006) The p53-targeting human phosphatase hCdc14A interacts with the Cdk1/cyclin B complex and is differentially expressed in human cancers. Mol Cancer. 2006 Jun 19;5:25.
Sun J, et. al. (2006) Interactions of sequence variants in interleukin-1 receptor-associated kinase4 and the toll-like receptor 6-1-10 gene cluster increase prostate cancer risk. Cancer Epidemiol Biomarkers Prev. 15(3):480-5.
Li T, Hu J, Thomas J, and Li L. (2005) Differential regulation of apoptosis by LPS and taxol in THP-1 cells. Molecular Immunology. 42: 1049-1055.
Sun J, Zheng S, Chang B, Li L, Li G, Liu W, Turner AR, Meyers DA, Isaacs EB, Xu J, Grönberg H. (2005) Sequence variants in Toll-like receptor gene cluster (TLR6-TLR1-TLR10) are associated with prostate cancer risk. Journal of the National Cancer Institute. 97: 525-532.
Chan C, Li L, McCall CE, Yoza B. (2005) Endotoxin Tolerance Disrupts Chromatin Remodeling and NF-
B Transactivation at the IL-1
Promoter. Journal of Immunology . 175: 461-468.
Huang YS, Li T, Sane D, Li L. (2004) IRAK1 serves a novel regulator essential for IL-10 gene expression. J Biol Chem . 279:51697-51703.
Li T, Hu J, and Li L. (2004) Regulation of Tollip by lipopolysaccharide in THP-1 cells. Molecular Immunology. 41 (1):85-92.
Li L . (2004) Regulation of innate immunity signaling and its connection with human diseases. Current Drug targets-Inflammation & Allergy. 3: 81-86 .
Jacinto R, Hu J, Hartung T, McCall CE, Li L. (2002) LPS and LTA-induced tolerance and cross-tolerance: Distinct alterations in IRAK. Journal of Immunology. 168: 6136-6141.
Moors M, Li L, Mizel S. (2001) Bacterial FliC protein activates macrophages via TLR-IRAK mediated pathway. Infection and Immunity. 69, 4424-4429.
Learn C, Boger S, Li L, McCall CE. (2001) Phosphortidyl-inositol-3-phosphate kinase selectively controls IL-1 RA protein production in tolerant cells. J Biol Chem. 276, 20234-9.
Liwu Li , Jack Dixon. (2000) Form, function, and regulation of protein tyrosine phosphatases and their involvement in human diseases. Seminars in Immunology. 12 (1), 75-84.
Liwu Li , Sue Coursat, Jean Hu, Charles McCall. (2000) Characterization of Interleukin-1 receptor associated kinase in normal and tolerant cells. Journal of Biological Chemistry.275, 23340-45.