2014 Ann Schreiber Mentored Investigator Award – Maria Giuseppina Baratta, PhD
Maria Giuseppina Baratta, PhD
Dana-Farber Cancer Institute
Novel therapeutic targets for High-Grade Serous Ovarian Carcinoma
Ovarian cancer is the leading cause of death from gynecologic malignancy in the U.S. Although response rates to initial surgery and platinum-based therapy can be 70-80%, the disease recurs in most patients and becomes increasingly platinum-resistant. Subsequent treatment with traditional single-agent chemotherapy results in response rates of approximately 20% at best, with a median time-to-progression of 2 to 3 months. New treatments are thus greatly needed, and the arena of targeted therapy is of great interest.
Recent data from the The Cancer Genome Atlas have revealed that high-grade serous ovarian cancers have limited point mutations aside from TP53, and significant alterations to multiple genes due to genomic amplifications or deletions. Despite how many genetic alterations have been described, very few targeted therapy have entered clinical trials. The main purpose of a targeted therapy is to impair the function of a gene that is essential for the survival of the cancer cell. In order to find these essential genes, I designed an experimental strategy aimed to test the role of a gene on the survival of a human ovarian cancer cell while growing into a tumor in a mouse. Indeed, I reasoned that cancer cell’s ability to survive had to be tested in an environment as close as possible to the physiological one. The approach I set up allowed me to screen the function of about 200 genes simultaneously in a single mouse-bearing tumor. I screened a total of 800 genes, including all human kinases and 300 putative human oncoprotein and found ~40 potential new druggable candidate genes. I now propose to test the function of these candidate target genes in Primary Ovarian Cancer cells and in tumors deriving from these cells. In addition, I propose to identify clinical characteristic that would predict sensitivity to a certain gene in order to identify a suitable population of patients that could benefit from a certain targeted therapy.
Dr. Maria Giuseppina Baratta is currently a postdoctoral research fellow at the Dana Farber Cancer Institute. Dr. Baratta received her M.Sc. degree in Biological Sciences from the University Federico II of Naples in 2004. She completed her Ph.D. in molecular medicine at the European School of Molecular Medicine (SEMM) of Naples in 2009, where she studied the role of ras oncogenes in thyroid cancers. In 2009 she joined Dr.David Livingston’s laboratory at the Dana Farber Cancer Institute to gain more experience in translational research. There she became very interested in ovarian cancer (OvCa) given the dearth of effective treatments available. Dr. Baratta’s research is now focused on the identification of novel therapeutic targets in OvCa. The rationale of her research is that assessing genes’ function in tumors rather than cultured cells, might reveal genes critical for OvCa cell viability that would be otherwise missed in a less pathophysiologically relevant setting. Following this idea she performed an shRNA-based negative selection screen in a human OvCa tumor xenograft model and she iscurrently selecting candidate target genes to test in primary-derived murine xenografts.