Historically, over more than four decade---at UC San Francisco, the NIH, Memorial Sloan Kettering Cancer Center, and now Weill Cornell Medicine---our group has worked on many aspects of retrovirology and cancer biology.
During the past decade, we have devoted special efforts to understand human lung cancer, especially adenocarcinomas driven by mutations in the gene encoding the epidermal growth factor receptor (EGFR). Much of this work was triggered by dramatic remissions observed in some patients with lung adenocarcinomas after treatment with tyrosine kinase inhibitors, leading to a description of lung-specific somatic mutations of EGFR that determine sensitivity and resistance to inhibitors of activated EGFR kinase.
Specific accomplishments include a recapitulation of mutant EGFR-induced and mutant K-Ras-induced lung cancers in mouse models in which the oncogene is controlled by doxycycline-dependent regulatory elements; collaborative studies that demonstrated additional mutations in lung adenocarcinomas from patients and in mouse models; identification of mutations that confer resistance to tyrosine kinase inhibitors; the role of other members of the EGFR family in lung carcinogenesis; studies of drugs that block the growth of lung adenocarcinoma cell lines by mechanisms other than kinase inhibition; description of the phospho-proteome in cells expressing mutant EGFR; and characterization of a mutant splicing factor, U2AF1, by gene editing of cultured cells and engineered mice.
Details about current projects are described on web pages that introduce readers to members of the laboratory and in papers that can be accessed through PubMed.