My laboratory is interested in the molecular mechanisms of metastasis in lung cancer. Metastasis is a poorly characterized process in cancer and focus on dissecting the mechanism of invasion from the primary tumor to distant sites is key to prevent the onset of this event. We focus on reverse-engineering differentially expressed genes obtained from genomic sequencing data of matched normal-primary tumor and brain metastasis patients in 3D lung models. We have identified a gene signature for metastasis, which are currently being tested using live cell and small animal imaging. The eventual goal is to reverse the onset of metastasis. Furthermore, our efforts focus on identifying immune genes that are altered in primary lung-brain tumor metastasis. Towards this effort, we adopt RNA and DNA sequencing of tumors, live cell fluorescent imaging and bioinformatics in the lab.
We are also interested to understand the functional significance of bromodomain containing proteins (BRD2, BRD3 and BRD4) across all cancers. Towards this effort, we have perturbed, using small molecule inhibitors, various cancers and identified key genes that regulate tumorigenesis in Myc dependent and independent manner. We are currently building small molecule variants towards bromodomains in collaboration with Dana-Farber Institute and testing them in tumor mice models. In this project, we use chemical conjugation strategies, genomic sequencing and small animal PET imaging to understand the overall mechanism of bromodomain targeting of tumors.