Therapeutic targeting of breast cancer metastasis: CDCP1 (CD318) and lipid metabolism.
CUB Domain Containing Protein 1 (CDCP1) is a transmembrane glycoprotein that is upregulated in many carcinomas and is correlated with poor prognosis in cancer patients. Our lab and others have shown that CDCP1 is necessary for migration of cancer cells in vitro and metastasis in mouse models of cancer. We are currently investigating the mechanism of CDCP1 activation at the plasma membrane so that we can target it therapeutically to inhibit CDCP1-mediated metastasis. Our recent findings highlighted its role in regulating lipid metabolism, opening the new line of investigation linking lipid metabolism and metastasis in breast cancer.
Synthetic lethality concept in cancer therapeutics.
We are investigating chemical synthetic lethal interactions in clear cell Renal Cell Carcinoma (ccRCC) deficient in the tumor suppressor von Hippel Lindau (VHL). Loss of VHL occurs in over 90% of patients and is a main driver of ccRCC tumor pathogenesis. Our lab has conducted a chemical library screen to identify novel drugs that specifically kill VHL-deficient ccRCC while sparing cells expressing VHL. We are currently validating the best hits from the screen and characterizing their mechanism of action. One of the lab’s research direction is to study the synthetic lethal interaction of VHL and CDK9, a transcriptional cyclin dependent kinases, and certain Rho GTPases that are active in the Rho/ROCK pathway.
Novel projects:
Lineage tracing of breast cancer stem cells (in collaboration with Chang Liu).
Therapeutically relevant 3D in vitro models of ccRCC for screening of therapeutics.