CANCER GENOMICS AND SIGNALING SECTION

Research Overview: We are interested in elucidating the molecular mechanisms of ovarian tumorigenesis in the hope that a better understanding of the pathways leading to ovarian cancer may provide new avenues for detection, diagnosis and therapy of this deadly disease.

1. Characterization of the roles and mechanisms of expression of claudin proteins in ovarian cancer: Our gene expression profiling of ovarian cancer previously revealed a large number of genes differentially expressed in ovarian cancer. Among the genes overexpressed in this disease, several members of the claudin family of proteins (claudin-3, -4, and -7) were found elevated in all grades and subtypes of ovarian cancer. This project focuses on the elucidation of the mechanisms of regulation of claudin proteins in ovarian cancer (transcriptional and post-transcriptional), as well as the roles of these proteins in the development of this disease. The elucidation of the roles of claudin proteins in ovarian cancer may have a significant impact on the detection, diagnosis, and treatment of this disease.

2. Analysis of gene expression associated with drug resistance: Resistance to chemotherapy is a major problem in the treatment of ovarian cancer, as half of the patients present with drug-resistant tumors. In addition, many ovarian tumors that are initially responsive to treatment often become refractory to chemotherapy. In order to study this problem, we have created a series ovarian cancer cell lines that are individually resistant to various chemotherapeutic drugs and are using microarrays to identify genes whose expression is altered in drug-resistant cells. The genes identified will be tested functionally for their roles in drug resistance.

3. Study microRNA expression in ovarian cancer: MicroRNAs (miRNAs) represent a class of small non-coding RNAs that control gene expression by targeting mRNAs and triggering either translation repression or RNA degradation. Emerging evidence suggests the potential involvement of altered regulation of miRNA in the pathogenesis of human cancer. Several miRNAs that are differentially expressed in ovarian cancer have been identified. These miRNAs are being validated in patients by RT-PCR and the potential targets of these miRNAs are being identified, validated, and tested for their roles in ovarian tumorigenesis.