The DePinho laboratory studies the molecular and biological processes governing the development of cancer, the basis for aging and degenerative diseases, and the maintenance of normal and cancer stem cells.
The laboratory takes an integrated genomics and biological systems approach to (1) discover and validate oncogenes and tumor suppressor genes, (2) elucidate the mechanisms driving cancer-associated chromosomal instability with an emphasis on telomeres and DNA damage checkpoint pathways, (3) define the role of stem cells and cancer stem cells and related developmental pathways in origins and maintenance of tumors, (4) develop and characterize mouse models of human cancers, particularly pancreas, colon, brain, and prostate, and (5) discover and rigorously validate new oncogenes to enable development of novel cancer therapies. Our mission is to convert basic knowledge into clinical endpoints that will impact on patient outcomes in meaningful ways.
- We have taken advantage of the large human cancer genome profiles to develop strategies to identify new cancer-specific vulnerabilities. These efforts have led to two new concepts -- collateral lethality and synthetic essentiality. We are using these concepts to help identify new cancer-specific therapeutic targets.
- In our multi-disciplinary Pancreatic Ductal Adenocarcinoma (PDAC) program – one of the most lethal human cancers – we are addressing a number of questions central to pathogenesis including metabolic dependencies, the role of lysosome scavenging, and the functional contribution of tumor immunity in PDAC.
- A major program in the lab has studied the role of telomerase in cancer, development and aging, and how telomere dynamics inter-relate to DNA damage and recombination pathways. Using a telomerase knockout mouse, we have pioneered cross-species comparative oncogenomics to enable the efficient identification of new oncogenes for drug discovery and new biomarkers for prognostication.
- Finally, our construction of inducible cancer models has permitted in vivo analyses of the complex symbiotic host-tumor cell interactions central to tumor maintenance and progression of diverse types of cancers.