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Lei Xu

Lei
Xu
Ph.D.
Assistant Professor
University of Rochester Medical Center
lei_xu@urmc.rochester.edu

We are interested in identifying cancer stem cell markers in malignant melanoma. Cancer stem cells are defined as the tumor initiation cells in cancer progression and have been postulated to be the chemoresistant population after systemic treatment of cancer. Understanding the biological properties of these cells will facilitate greatly the process of cancer control. Metastasis is a process whereby cancer cells migrate to a distant organ and proliferate there to form a tumor mass, therefore metastatic cancer cells are assumed cancer stem cells. A population of cells that produce more metastases thus must contain more cancer stem cells than a population of cells that produce fewer metastases. Based on this rationale, we propose to identify more cancer stem cell markers in malignant melanoma, which is highly resistant to current therapies, using cell lines with increased metastatic abilities. We previously generated melanoma cell lines with increased metastatic abilities using an experimental metastasis model. Using DNA microarray analyses, we compared the gene expression profiles between the samples from the derived cells and those from the parental line and identified the differentially expressed genes. These genes were found to correlate with the aggressiveness of human melanoma metastases and a poor survival in melanoma metastases-carrying patients, suggesting strongly their relevance to human melanoma progression. We hypothesize that they might be melanoma stem cell markers and will test this in xenograft animal models.

Select Publications: 

Li S, Jin Z, Koirala S, Bu L, Xu L, Hynes RO, Walsh CA, Corfas G, Piao X. GPR56 regulates pial basement membrane integrity and cortical lamination. J Neurosci. 2008 May 28;28(22):5817-26.

Xu L, Shen SS, Hoshida Y, Subramanian A, Ross K, Brunet JP, Wagner SN, Ramaswamy S, Mesirov JP, Hynes RO. Gene expression changes in an animal melanoma model correlate with aggressiveness of human melanoma metastases. Mol Cancer Res. 2008 May;6(5):760-9.

Xu L, Hynes RO. GPR56 and TG2: possible roles in suppression of tumor growth by the microenvironment. Cell Cycle. 2007 Jan 15;6(2):160-5.

Xu L, Begum S, Hearn JD, Hynes RO. GPR56, an atypical G protein-coupled receptor, binds tissue transglutaminase, TG2, and inhibits melanoma tumor growth and metastasis. Proc Natl Acad Sci U S A. 2006 Jun 13;103(24):9023-8.

Xu L, Strome S. Depletion of a novel SET-domain protein enhances the sterility of mes-3 and mes-4 mutants of Caenorhabditis elegans. Genetics. 2001 Nov;159(3):1019-29.

Xu L, Paulsen J, Yoo Y, Goodwin EB, Strome S. Caenorhabditis elegans MES-3 is a target of GLD-1 and functions epigenetically in germline development. Genetics. 2001 Nov;159(3):1007-17.

Xu L, Fong Y, Strome S. The Caenorhabditis elegans maternal-effect sterile proteins, MES-2, MES-3, and MES-6, are associated in a complex in embryos. Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5061-6.

Williams C, Xu L, Blumenthal T. SL1 trans splicing and 3'-end formation in a novel class of Caenorhabditis elegans operon. Mol Cell Biol. 1999 Jan;19(1):376-83.