Research in the laboratory is focused on genetic, molecular and functional studies on altered genes with a specific focus on ovarian and breast cancer. Several known and novel down regulated genes that play important roles in early stages of ovarian carcinogenesis were identified utilizing high throughput screening techniques such as Differential-Display PCR, cDNA microarray analysis and suppression subtraction cDNA libraries (1-3). Current studies are aimed at determining the functional consequences of loss of these potential tumor suppressor genes in terms of apoptosis, angiogenesis, metastasis and chemoresponse in ovarian and breast cancer. Specific Projects are as follows:

Epigenetic Silencing of Novel Candidate Tumor Suppressor Genes in Ovarian Cancer: Studies are focused on the mechanisims of down regulation such as loss of heterozygosity, mutational analysis by DHPLC and methylation analysis by Methylation Specific PCR (MS-PCR). We have shown that the loss of expression of a novel gene MCJ (DNAJD1) is due to loss of an allele by deletion and methylation of the other (1). Current studies are focused on the functional characterization of DNAJD1.

Ongoing studies on another novel down regulated gene on the X chromosome (TCEAL7) (6) revealed that the loss of expression of TCEAL7 is due to methylation of the active expressed allele on the X chromosome. Functional consequence of loss of TCEAL7 is under way.

Role of HSulf-1 in ovarian and breast cancer apoptosis, angiogenesis and drug resistance: We recently identified HSulf-1 that modulates heparin-binding growth factor signaling in ovarian and breast cancer (5). Current studies are focused on defining the role of HSulf-1 in angiogenesis, apoptosis and drug resistance in both ovarian and breast cancer.

Functional consequences of loss of HtrA1 in cancer We recently identified the pro-apoptotic serine protease HtrA1 as a down-regulated gene in a majority of ovarian cancer cell lines as well as primary ovarian tumors (4). HtrA1 confers cisplatin and taxol sensitivity by targeting microtubules for degradation. Current studies are focused on the role of HtrA1 in apoptosis, metastasis and chemoresponse.