e-mail- xhuang@med.wayne.edu

Education:
M.D., Medicine, Nanhua University School of Medicine, Hunan, 1987
Ph.D., Immunology, Sun Yat-sen University School of Medicine, Guangzhou, 1994

Training:
1994-1996, Postdoctoral Research Fellow, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan

Professional and Faculty Appointments:
1996-1999, Research Associate, Karmanos Cancer Institute, Detroit, Michigan
1999-2001, Research Scientist, R&D center, Pfizer Pharmaceutical Inc., Ann Arbor, Michigan
2001-2005, Research Scientist, Anatomy & Cell Biology, Wayne State University, Detroit, Michigan
2005-present, Assistant Professor (res. at ocu. inf.), Anatomy & Cell Biology, WSU, Detroit, Michigan

Major Research Interests:
Ocular infection: molecular and immunopathogenic mechanisms; Toll-like receptors (TLRs); Triggering receptors expressed on myeloid cells (TREMs).

Current Research:
Keratitis induced by Pseudomonas aeruginosa (P. aeruginosa) is one of the most common and destructive of bacterial diseases, especially in extended-wear contact lens users. Compelling evidence suggests that innate and adaptive immune responses play a critical role in bacterial keratitis, and both bacterial (e.g., LPS) and host factors released from infiltrating cells during infection contribute to a rapidly progressing liquefactive stromal necrosis. One focus of my interest is the role of Toll-like receptors (TLR) in bacterial keratitis. TLRs are a family of proteins that are involved in the initial phase of host defense against invading pathogens. It act as primary sensors of microbial products and initiate innate immunity through activation of transcription factors leading to induction of strong immune and proinflammatory responses. The goal of the studies proposed in this application is to elucidate the role of TLR/IL-1R in the innate and adaptive immune response to experimental P.aeruginosa corneal infection resulting in corneal perforation (B6) vs. healing (BALB/c). Another focus of my study is the role of Triggering receptors expressed on myeloid cells (TREMs) in ocular infection. TREMs are a novel family of receptors that have recently been implicated as key molecules in the development of the innate and adaptive immune response. Although nothing is known about the role of TREMs in the cornea (or in the eye), our preliminary data provide substantive evidence that TREM-1 and TREM-2 are disparately expressed in the cornea of B6 and BALB/c mice challenged with P. aeruginosa. Studies aimed at understanding the molecular mechanisms, particularly the early events of intracellular signaling and immunopathological processes involved in the immune response to P. aeruginosa keratitis may provide a solution not only for control of bacterial keratitis, but also for other diseases with an excessive inflammation. The goal of this proposal is to elucidate the role of TREM-1 and TREM-2 in the innate and adaptive immune response to P. aeruginosa infection resulting in corneal perforation (susceptibility) vs. healing (resistance). It is expected that our findings will reveal potential targets for early intervention and/or treatment of P. aeruginosa keratitis.

Selected publications:

1.	Huang X, Du W, Barrett RP and Hazlett LD. ST2 is essential for Th2 responsiveness and resistance to Pseudomonas aeruginosa keratitis. Invest Ophthalmol Vis Sci. 48:4626-4633, 2007. Medline
2.	Huang X, Hazlett LD, Du W. and Barrett RP. SIGIRR promotes resistance against Pseudomonas aeruginosa keratitis by down-regulating type-1 immunity and IL-1R1 and TLR4 signaling. J Immunol. 177:548-556, 2006. Medline
3.	Huang X, Du W, McClellan SA, Barrett RP and Hazlett LD. TLR4 is required for host resistance in Pseudomonas aeruginosa keratitis. Invest Ophthalmol Vis Sci. 47:4910-4916, 2006. Medline
4.	Huang X, Barrett RP, McClellan SA and Hazlett LD. Silencing Toll-like receptor-9 in Pseudomonas aeruginosa keratitis. Invest Ophthalmol Vis Sci. 46:4209-4216, 2005. Medline
5.	Lighvani S, Huang X, Trivedi PP, Swanborg RH and Hazlett LD. Substance P regulates natural killer cell interferon-gamma production and resistance to Pseudomonas aeruginosa infection. Eur J Immunol. 35(5):1567-1575, 2005. Medline
6.	McClellan SA, Huang X, Barrett RP, van Rooijen N and Hazlett LD. Microphages restrict Pseudomonas aeruginosa growth, regulate polymorphonuclear neutrophil influx, and balance pro- and anti-inflammatory cytokines in BALB/c mice. J Immunol. 170:5219-5227, 2003. Medline
7.	Huang X and Hazlett LD. Analysis of Pseudomonas aeruginosa corneal infection using an oligonucleotide microarray. Invest Ophthalmol Vis Sci. 44:3409-3416, 2003. Medline
8.	Huang X, McClellan SA, Barrett RP and Hazlett LD. IL-18 contributes to host resistance against infection with Pseudomonas aeruginosa through induction of IFN-gamma production. J Immunol. 168:5756-5763, 2002. Medline
9.	Taub JW, Huang X, Ge Y, Dutcher JA, Stout ML, Mohammad RM, Ravindranath Y and Matherly LH. Cystathionine-beta-synthase cDNA transfection alters the sensitivity and metabolism of 1-beta-D- arabinofuranosylcytosine in CCRF-CEM leukemia cells in vitro and in vivo: a model of leukemia in Down Syndrome. Cancer Res. 60:6421-6426, 2000. Medline
10.	Taub JW, Huang X, Matherly LH, Stout ML, Buck SA, Massey GV, Becton DL, Chang MN, Weinstein HJ and Ravindranath Y. Expression of chromosome 21-localized genes in acute myeloid leukemia: differences between Down Syndrome and non-Down Syndrome blast cells and relationship to in vitro sensitivity to cytosine arabinoside and daunorubicin. Blood 94:1393-1400, 1999. Medline

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