Research and Clinical Interests
I am a lung cancer specialist with a particular interest in how RNA interference (RNAi) can regulate cancer metastases. Because metastases are responsible for the death of nearly all cancer patients, the ability to control this process is vital. In collaboration with our Carolina Center of Cancer Nanotechnology Excellence, I am studying how nanoparticle-based platforms can be exploited to target the metastatic process. Currently I have three areas of focus centered on this problem:
First, our group helped discover and characterize how the miR-200 family regulates tumor angiogenesis. We found that miR-200 directly targets IL-8 and CXCL1 cytokines secreted from cancer cells, which are important mediators of angiogenesis and metastasis. We demonstrated that miR-200 regulation of angiogenesis is a novel regulatory network across several cancer types; namely lung, ovarian, renal and triple-negative breast adenocarcinomas. Several metastatic models demonstrated that nanoparticle-mediated delivery of miR-200 members could potently silence IL-8 and CXCL1, leading to therapeutic inhibition of angiogenesis and metastases. Current efforts are on further characterizing how this miRNA family regulates cancer progression.
Second, I am studying novel miRNA mediators of lung cancer metastasis. Our group is utilizing the Cancer Genome Atlas dataset to investigate key regulatory networks within lung adeno- and squamous carcinomas. We are establishing new metastases models to study candidate miRNAs of interest. The ultimate goal will be to explore and develop systemically delivered miR-based therapeutics to inhibit metastases in these models.
Finally, since the classic KRAS oncogene is largely considered “non-druggable”, I am investigating how nanoparticle delivery of KRAS siRNAs can be used to therapeutically inhibit KRAS-driven cancers. Using metastatic models of lung and colorectal cancers, we have found that systemically delivered KRAS siRNAs can potently inhibit metastases formation. We are interested in further developing this approach as a novel therapeutic to enter early-phase clinical trials.