Our research is focused on understanding of cancer pathogenesis with a particular attention to expression of phenotypical traits in the context of cell lineage development and cellular interactions with microenvironment. Success of such studies greatly depends on the availability of comprehensively characterized immunocompetent mouse models that accurately mimic human cancers. Therefore, we have established a series of genetically defined mouse models of cancers associated with alterations of p53 and Rb tumor suppressors and their pathways. The rationale for choosing these genes is two-fold: (1) alterations in p53 and Rb and/or their pathways occur in over 80% of all human cancers and (2) multiple functions of p53 and Rb have been extensively described and characterized at the molecular and cellular levels providing an appropriate starting point for our studies. Conventional knock out of the Rb gene leads to embryonic lethality, while mice with a single copy of wild-type Rb or complete lack of p53 succumb to rapidly progressing neoplasms with a limited relevance to major human cancers associated with deficiency of these genes. Thus, mouse models allowing cell type-restricted spontaneous or conditional inactivation of p53 and/or Rb have been either generated by our lab or received from other investigators.

Our main areas of interest include understanding the role of stem cell compartment in carcinogenesis, studies of epithelial ovarian cancer pathogenesis and modeling metastasis. We are also interested in pursuing technology-oriented research based on cross-disciplinary collaborations are described below.