Functional Genomics and High Throughput Screening to Identify New Targets for Cancer Therapy.
My laboratory focuses on exploiting the weaknesses of cancer cells to identify targeted, less toxic cancer therapies. Mutation in oncogenes and tumor suppressor genes, while essential for driving cancer cell growth also create weaknesses. Our laboratory utilizes functional genomics to elucidate these conditional survival pathways. RNA interference (RNAi) combined with high throughput technology enables us to interrogate the human genome for genes that are essential for the viability of cancer cells, thus allowing the unbiased identification of these "Achilles’ heels". These synthetic lethal genes constitute potential drug targets.
- Using this approach, we have identified new druggable targets and we are currently testing inhibitors in pre-clinical studies. Thus far we have focused on identifying synthetic lethal pathways with the MYC oncogene. Aberrant expression of Myc is common to many human cancers and our laboratory currently focuses on neuroblastoma, ovarian, and breast cancer.
- We are also currently optimizing high throughput screens of patient-derived cultures with the objective of creating a database of cancers based on functional genomic assays. This approach, integrated with other “omics” data, will enable us to select gene candidates for drug development as well as develop a personalized diagnostic tool to select targeted treatments for a given patient.
- As of 2013, our laboratory, together with four other groups here at the Center, received a $4 million grant from the NCI’s Office of Cancer Genomics Cancer Drug Target Discovery and Development Program (CTD2), to lead discovery of novel drug targets for cancer.