Our laboratory studies cell signaling in normal development and disease. We have a particular emphasis on members of the protein-tyrosine phosphatase (PTP) superfamily (especially SHP2 and PTP1B), and on the regulation and role of the RAS/ERK pathway in RASopathies (a family of germ line disorders caused by RAS/ERK pathway mutations) and cancer. We also have a substantial program in breast cancer functional genomics and in the biology and modeling of high grade serous ovarian carcinoma (HGSOC). We employ a wide range of cell biological, biochemical and mouse and human (hESC/iPSC) genetic approaches to study these questions.
Current work is aimed at identifying the mechanism by which SHP2 regulates RAS, the effect of SHP2 inhibitors alone and in combination with other agents on tumor cells and their microenvironment, mechanisms of resistance to SHP2 inhibitors, and the role of SHP2 in senescence and the DNA damage response. Other projects includes the role of PTP1B in RNF213 regulation and hypoxia sensitivity the role of ERK isoforms on myeloproliferative disease and other malignancies and the utility of high dose vitamin C alone and in combination with other agents in the treament of leukemia, identifying novel targets for breast cancer using lentiviral shRNA dropout screening and large scale integrative genomic analysis, and the cell-of-origin and novel organoid and transplant models of high grade serous ovarian cancer.