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 (i) discover and validate oncogenes and tumor suppressor genes, (ii) elucidate the mechanisms driving cancer-associated chromosomal instability with an emphasis on telomeres and DNA damage checkpoint pathways, (iii) define the role of stem cells and cancer stem cells and related developmental pathways in origins and maintenance of tumors, (iv) the development and characterization of mouse models of human cancer particularly pancreas, colon, brain, breast and lymphoid systems, and (v) the discovery and development of novel cancer therapies directed against newly discovered and rigorously validated oncogenes.
Some of our ongoing efforts have centered on how mouse genetics and genomics can be used to dissect the molecular mechanisms and biological processes governing the genesis and maintenance of tumorigenesis. We have elucidated the genetic and biochemical relationship between Rb, p53 and PI3K pathways, particularly p16INK4a, p19ARF and FoxOs, and have delineated an intimate link between pathways that control cellular senescence and those that regulate cell cycle entry or cell survival as well as stem cell homeostasis
In our multi-disciplinary programs in glioblastoma (GBM) and Pancreas Cancer (PDAC), two of the most lethal human cancers, we are addressing a number of questions central to pathogenesis including (i) the tumor's cell of origin and how the state of cellular differentiation influences the oncogenic actions of prominent glioma-relevant mutations, (ii) how such mutations contribute to specific biological and clinical characteristics of the disease, and (iii) whether these are required for both the genesis and maintenance of these cancers and whether such knowledge can inform drug development.
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. Finally, our construction of inducible cancer models has permitted an in vivo analysis of the complex symbiotic host-tumor cell interactions central to tumor maintenance and progression of diverse types of cancers.
- Mouse models of cancer
- Glioblastoma multiforme (GBM)
- Multiple myeloma