| Send E-mail to: wli@usc.edu | |
| Telephone: 323-865-0618 | Fax: 323 865-0105 |
| Office: NOR 6320 | Mail Code: 9176 HSC |
Education:
BS 1982 Biology - Xinjiang University, Urumqi, China
English Certificate 1984 The CUSBEA (China-US joint) Program - Zhongshan University / UCLA
MS 1988 Molecular Biology & Development - Albert Einstein College of Medicine, New York, NY
PhD 1991 Molecular Biology & Development - Albert Einstein College of Medicine, New York, NY
Postdoctoral Research Fellowship:
1991 - 1993 New York University Medical Center, New York, NY
Started at USC: 1999
Research Topics: Growth Factors and Receptors, Protein Phosphorylation and Signal Transduction, Cell Proliferation and Migration, Identification of New Drug Targets in Wound Healing and Cancer Progression
Research Description
A. Significance and Focus
Our research targets two clinical problems: wound repair and cancer, which are higly related. The focus is on the mechanism of migration of the cells involved, i.e. how these cells "walk and run". Without migration, wounds willl not heal and cancer cells cannot form cancer (through invasion and metastasis in human tissues). We want to figure out the signal transduction pathway that controls cell migration. Then, we want to identify the therapeutic targets along this signaling pathway to promote cell migration in non-healing wounds and to block cell migration in cancer.
B. Known and Unknown
a) What we know: cell migration is result of repeated cycles of cytoskeletal-mediated protrusion, polarization, formation of adhesive contacts, cell contraction, and retraction at the trailing edge. Initiation of these sequential processes is triggered by two extracellular microenvironmental cues, extracellular matrices (ECMs) and soluble growth factors (GFs). In our bodies, ECMs are substratum-immobilized molecules, whereas GFs are soluble and circulating polypeptides.
b) What we do not know and want to know: the key regulators of cell migration during wound healing and during cancer progression.
C. Selected Achievements of the Past 5 Years
1) Human serum, but not plasma, promotes keratinocyte migration (LANCET, 2003, IF, 27, PubMed).
2) PDGF-BB is the major factor in human blood that stimulates dermal fibroblast motility (Mol. Biol. Cell, 2004, IF: 7.1 PubMed).
3) TGF-beta3 in human serum serves as a "traffic controller" for the order of dermal and epidermal cell motility during wound healing (J. Cell. Biol. 2006, IF: 10.2, PubMed).*
* This publication was selected as "Editor’s Choice" by Science.
4) Heat shock protein 90 (hsp90) is secreted by human skin cells during wound healing to promote dermal and epidermal cell motility in vitro and wound healing in vivo (EMBO J, 2007, IF: 10.3 PubMed)
5) The SH2/SH3 Nck adapter links tyrosine kinase receptors to actin cytoskeleton by controlling paxillin stability (Mol. Cell. Biol, 2007, IF: 7.9, PubMed )
6) The wound-healing function of Heat shock protein 90 (hsp90) resides in the middle domain of hsp90--no need for its ATPase or co-factor binding domains (Mol. Cell. Biol, 2008, IF: 7.9, PubMed )
7) Discovery of "hypoxia > secretion of hsp90 > LRP1 > cell motility" autocrine loop and its implications in cancer progression (J. Cell Sci, 2009, IF: 6.5)
D. Ongoing Research Projects
1) How secreted heat shock protein-90 (hsp90) promotes cell migration in vitro and wound healing in animal models. The goal is to prove that extracellular hsp90 is a novel and effective drug for wound healing.
2) The importance for the "hypoxia > secretion of hsp90 > LRP1 receptor > cell motility" autocrine signaling in breast cancer invasion and metastasis.
3) The anti-motility signaling by TGF-beta.
E. Drug-related R&D
"Topical application of Hsp90 to enhance wound healing" (US patent pending)
10 Selected Publications:
Click here to view all the publications for this faculty
Woodley DT,Fan J,Cheng CF,Li Y,Chen M,Bu G,Li W - Participation of the lipoprotein receptor LRP1 in hypoxia-HSP90alpha autocrine signaling to promote keratinocyte migration. - J Cell Sci [2009] May 15;122(Pt 10):1495-8 PubMed
Guan S,Fan J,Han A,Chen M,Woodley DT,Li W - Non-Compensating Roles between Nckalpha and Nckbeta in PDGF-BB Signaling to Promote Human Dermal Fibroblast Migration. - J Invest Dermatol [2009] Feb 26;(): PubMed
Woodley DT,Hou Y,Martin S,Li W,Chen M - Characterization of molecular mechanisms underlying mutations in dystrophic epidermolysis bullosa using site-directed mutagenesis. - J Biol Chem [2008] Jun 27;283(26):17838-45 PubMed
Cheng CF,Fan J,Fedesco M,Guan S,Li Y,Bandyopadhyay B,Bright AM,Yerushalmi D,Liang M,Chen M,Han YP,Woodley DT,Li W - Transforming growth factor alpha (TGFalpha)-stimulated secretion of HSP90alpha: using the receptor LRP-1/CD91 to promote human skin cell migration against a TGFbeta-rich environment during wound healing. - Mol Cell Biol [2008] May;28(10):3344-58 PubMed
Cheng CF,Fan J,Bandyopahdhay B,Mock D,Guan S,Chen M,Woodley DT,Li W - Profiling motility signal-specific genes in primary human keratinocytes. - J Invest Dermatol [2008] Aug;128(8):1981-90 PubMed
Guan S,Chen M,Woodley D,Li W - Nckbeta adapter controls neuritogenesis by maintaining the cellular paxillin level. - Mol Cell Biol [2007] Sep;27():6001-11 PubMed
Li W,Li Y,Guan S,Fan J,Cheng CF,Bright AM,Chinn C,Chen M,Woodley DT - Extracellular heat shock protein-90alpha: linking hypoxia to skin cell motility and wound healing. - EMBO J [2007] Mar 7;26(5):1221-33 PubMed
Woodley DT,Remington J,Huang Y,Hou Y,Li W,Keene DR,Chen M - Intravenously injected human fibroblasts home to skin wounds, deliver type VII collagen, and promote wound healing. - Mol Ther [2007] Mar;15():628-35 PubMed
Bandyopadhyay B,Fan J,Guan S,Li Y,Chen M,Woodley DT,Li W - A "traffic control" role for TGFbeta3: orchestrating dermal and epidermal cell motility during wound healing. - J Cell Biol [2006] Mar 27;172(7):1093-105 PubMed
Fan J,Guan S,Cheng CF,Cho M,Fields JW,Chen M,Denning MF,Woodley DT,Li W - PKCdelta clustering at the leading edge and mediating growth factor-enhanced, but not ecm-initiated, dermal fibroblast migration. - J Invest Dermatol [2006] Jun;126():1233-43 PubMed
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