The University of Texas MD Anderson Cancer Center
Departments of Surgical Oncology and Cancer Biology
Our laboratory is interested in the identification and characterization of molecular events associated with melanoma progression in order to identify new prognostic factors and targets for anti-tumor and anti-metastasis therapy. In collaboration with Menashe Bar-Eli, Ph.D., we have demonstrated that the transition of melanoma to the metastatic phenotype is associated with the loss of expression of the transcription factor AP-2; AP-2 has also been shown to regulate several genes involved in the progression of human melanoma. To further investigate the role of AP-2 in the progression of human melanoma, we inactivated AP-2 in melanoma cell lines by using the dominant-negative AP-2, or AP-2B gene, and have recently shown that inactivation of AP-2 contributes to the progression of melanoma at least partially by a deregulation of the MMP-2 gene. We are also investigating additional potential downstream targets by gene expression profiling.
Using a comprehensive clinicopathologic melanoma database that contains well-characterized patient data as well as associated tissue, we have also begun to explore new potential prognostic markers in melanoma. Using gene expression profiling, our goal is to identify gene expression profiles associated with a favorable or unfavorable prognosis, by correlating particular gene expression profiles with clinical outcomes, to develop more individualized treatment approaches and better prognostic models. We have initiated gene expression profiling studies for human primary melanoma as well as metastatic melanoma in an effort to identify new target genes as well. More recent investigations have led to an effort to explore the molecular basis for lymphatic metastases in melanoma patients (a clinically relevant problem for this disease). We have recently begun to explore the role of various genes involved in the process of lymphangiogenesis including VEGF-C, VEGF-D and their common receptor, VEGFR-3.
A tutorial performed in my laboratory would afford the interested student the opportunity to participate in any of these projects or related themes. A variety of molecular biologic and cell biologic techniques are utilized to investigate metastases-related gene expression in melanoma. These methods include PCR, Northern and Western blot analysis, transfection studies, immunohistochemical staining and in situ hybridization of human specimens, promoter construct assays, animal studies, and microarray techniques.
Education & Training
M.D. - Cornell University Medical College - 1990