Wei Li Professor Dermatology Keck School of Medicine

Education:
BS 1982 Biology - Xinjiang University, People's Republic of China
MS 1988 Molecular Biology & Development - Albert Einstein College of Medicine
PhD 1991 Molecular Biology & Development - Albert Einstein College of Medicine, New York

Postdoctoral Research Fellowship:
1991-1993 New York University Medical Center

Started at USC: 1999

Research Topics: Signal Transduction

Research Description

The goal of Dr. Li’s research is to find new therapeutic targets to heal chronic human skin wounds faster with less scaring and to stop melanoma (a deadly skin cancer) cell migration at its early epidermal stage. The focus is on understanding the signal transduction for cell motility, which is a rate-limiting step for both skin wound healing and melanoma progression. The working theme is how the motility signal initiates at the cell surface by growth factors, propagates in the cytosol by signaling networks and executes by newly expressed intra/extra cellular secreted gene products.

A schematic four-step model for cell migration is shown in Figure 1 (see below) .

Cell migration is the 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 mainly triggered by two extracellular microenvironmental cues, extracellular matrices (ECMs) and soluble growth factors (GFs), which act synergistically to stimulate optimal cell migration. In vivo, ECMs are substratum-immobilized molecules. In contrast, GFs are mostly soluble polypeptides. Cell migration towards a substratum-bound ECM gradient in the absence of growth factors is referred to as "haptotaxis". Cell migration toward a gradient of soluble GFs is known as "chemotaxis". Our missions are to reveal the nature of the GFs involved in human skin wound healing and their acting codes.

Recent major findings from Dr. Li's Lab:

1) Human serum, but not human plasma, promotes keratinocyte migration (LANCET, 2003 PubMed).

2) PDGF-BB is the major factor in human blood that controls dermal fibroblasts’ motility (Mol. Biol. Cell, 2004 PubMed).

3) TGF-alpha is the major factor in human blood that controls epidermal keratonocytes’ motility (J. Inv. Derm, 2006 PubMed).

4) The naturally occurring "plasma-to-serum-to-plasma transition" serves as a "traffic control" for the dermal and epidermal cell motility during wound healing (J. Cell. Biol. 2006 PubMed). This work was selected as an "Editor’s Choice" by Science (Science, 2006).

5) Heat shock protein 90 (hsp90) is secreted to outside of skin cells to promote dermal and epidermal cell motility in vitro and wound healing in vivo (EMBO J, 2007 PubMed)

6) The SH2/SH3 Nck adapter links tyrosine kinase receptors to actin cytoskeleton by controlling paxillin stability (MCB, 2007 PubMed )

Current research projects: *

1) The mechanism by which hsp90 promotes skin cell migration in vitro and wound healing in vivo (see the working model). The goal is to gain sufficient evidence for taking hsp90 to clinical trials.

2) The anti-motility signaling by TGF-beta. Impact of this study is high and broad, due to the critical role of the TGF-beta family cytokines not only in wound healing, but also in development, cancer metastasis, heart disease, just mention a few.

3) To identify the physiological factor in skin epidermis that helps melanoma cells "travel" and penetrate to the dermis. Such a factor will have strong therapeutic potentials for preventing melanoma.

* These projects are particularly focused so that a steady-state production of high-impact publications is anticipated for those motivated graduate students who want to make a difference and do it quicker.

Selected Publications

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 ] Apr 30; . 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 ] Mar 6; . 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(17):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(3):628-35 . PubMed

Li Y, Fan J, Chen M, Li W, Woodley DT. - Transforming growth factor-alpha: a major human serum factor that promotes human keratinocyte migration. - J Invest Dermatol [ 2006 ] Sep;126(9):2096-105 . 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(6):1233-43 . PubMed

Li W, Dasgeb B, Phillips T, Li Y, Chen M, Garner W, Woodley DT. - Wound-healing perspectives. - Dermatol Clin [ 2005 ] Apr;23(2):181-92 . PubMed