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Patrice Jean-Luc Morin, Ph.D., Senior Investigator Chief, Cancer Genomics and Signaling Section Laboratory of Cellular and Molecular Biology E-mail: morinp@grc.nia.nih.gov Bibliography |
| Biography: Dr. Morin received his Ph.D. from Boston University in 1995. He then completed postdoctoral training at the Johns Hopkins Oncology Center before accepting his current position at the National Institute on Aging in Baltimore. Dr. Morin also holds an Assistant Professor position at the Johns Hopkins School of Medicine, Department of Pathology. |
| Research Overview: Our laboratory's interest is twofold: molecular genetics of ovarian cancer and the role of the APC/b-catenin pathway in human cancer. |
| SAGE Analysis of Normal Ovary and Ovarian Cancer: It is well documented that, in the process of going from normal to malignant, cells reprogram their gene expression. However, consistent changes that could be useful for diagnosis and/or therapy have remained elusive for most tumor types, including ovarian cancer. SAGE, one of the more powerful techniques currently available for the quantitative study of gene expression, is being used in our laboratory to analyze normal ovarian tissue, primary ovarian tumors and ovarian cancer cell lines. We have identified hundreds of transcripts differentially expressed during ovarian tumorigenesis. Interestingly, several of these genes represent novel genes. We are currently characterizing many of the differentially expressed transcripts using a variety of techniques including immunohistochemistry, quantitative (real-time) RT-PCR and functional assays. Some of these genes may become targets of novel strategies for early detection and/or mechanism-based therapy of ovarian cancer. |
| Search for Genetic Alterations in Ovarian Cancer: Surprisingly little is known about the molecular alterations in ovarian cancer. We have established a panel of matched normal tissue and primary ovarian cancer specimens and are using this panel, in conjunction with ovarian cancer cell lines, to identify genes important in ovarian tumorigenesis. Techniques used include representational difference analysis (RDA) and LOH studies. Of particular interest are chromosomal regions on Xq, 11p and 6q which are frequently lost in ovarian cancers, suggesting the presence of tumor suppressor genes important in ovarian tumorigenesis. We have recently suggested that the GPC3, a gene located at Xq26 and previously implicated in an overgrowth syndrome, may be silenced during ovarian tumorigenesis. |
| The APC/b-catenin Pathway in Human Cancers: The APC/b-catenin pathway has recently been shown to be involved in human cancer. APC, a gene mutated in 80% of all colon cancers, is crucial for downregulation of b-catenin and TCF-mediated transcription. Moreover, colon tumors containing wild-type APC, frequently contain activating mutations in b-catenin, emphasizing the importance of this pathway for colon cancer progression. In addition, b-catenin has now been found to be mutated in many tumors types such as ovarian, prostate and skin cancers. We are studying the regulation of this pathway in normal and in cancer cells using a number of approaches, including the construction of stable cell lines expressing inducible versions of the b-catenin protein. One such line exhibits a highly inducible b-catenin protein and has been used to generate SAGE libraries. These experiments should help us identify genes that are transcriptionally induced by the b-catenin/TCF transcription complex and that may be relevant to a wide variety of human cancers. |
| Address for Correspondence: |
| Cancer Molecular Genetics Unit Laboratory of Cellular and Molecular Biology Gerontology Research Center National Institute on Aging 5600 Nathan Shock Drive Baltimore, MD 21224-6825 Phone: 410-558-8506 Fax: 410-558-8386 |
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