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Research Directions: next
ONCOGENOMICS:
Since 2003, we have started the oncogenomic program and the purpose is to identify new genes with oncogenic or tumor suppressor potential in high-grade ovarian carcinoma, the most common and lethal gynecological neoplastic disease, through genome wide analysis including digital karyotyping and SNP array.
• Characterization of a new amplified gene, Rsf-1/HBXAP (a chromatin remodeling gene), in ovarian cancer by demonstrating its oncogenic potential and validating Rsf-1 gene amplification as a genetic marker to predict aggressive clinical behavior in ovarian serous carcinoma patients in multi-institutional studies. Current efforts involve the study of molecular mechanisms underlying its oncogenic potential and the setup of a clinical trial to evaluate its clinical potential as a prognostic marker in a large scale study. References: 19, 20
• Characterization of another amplified genes, Notch-3, in ovarian cancer and demonstrated its essential role in tumor growth and survival. Inducible transgenic models (cre-loxp) will be used to overexpress Notch-3 on mouse ovaries in the future. This orthotopic animal model (in the background of p53 +/+ and p53-/-) will help to define the role of Notch-3 amplification/overexpression + p53 mutations in the development of ovarian cancer. Currently, we are identifying the downstream targets controlled by the Notch-3 pathway. Gamma secretase inhibitors and novel natural compounds that inactivate Notch-3 signaling will be tested to determine the potential therapeutic applications in a mouse model in the future. Reference: 21
• Characterization of a homozygous deleted gene, MKK4, in ovarian and colorectal cancer. Somatic knock out cells (MKK4 -/-) DLD1 and HCT116 cell lines have been established by us and will be used to study how MKK4 signaling contributes to the invasive phenotype in cancer cells with MKK4 deletion or downregulation. Reference: 22
• Mutational analysis in low-grade and high-grade ovarian serous carcinoma. Future study will continue sequencing kinase family, phosphatase family and candidate chromosomal instability genes in purified ovarian tumor cells from the Ovarian Cancer Tumor Bank we established. References: 3, 23.
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