Genomic instability is a major driving force for tumorigenesis. Mammalian cells use several mechanisms to maintain their genome integrity, including high fidelity DNA replication in S-phase, accurate chromosome segregation in M-phase, precise and error-free repair of DNA damage throughout the cell cycle, and a series of highly coordinated cell cycle events. Thus, a dysregulation of any components of the above processes is risk a factor for cancer development. At the same time, many of the genes involved in genome maintenance are pleiotropic and have overlapping functions in essential cellular processes critical for normal development.
My laboratory aims at understanding the complex roles of several essential genes in the BRCA-network and DNA damage response pathways in both tumorigenesis and development. Three current projects are focused on: 1) the fundamental mechanisms by which the genome integrity is maintained by several proteins in the BRCA-network, and how these understandings can be translated into applications of cancer interventions. 2) the confounding roles of an essential protein (BCCIP) and interaction partners in tumorigenesis and development through the genome maintenance and ribosome biogenesis; and 3) the regulation of DNA repair and cell fate determination by methylations of non-histone proteins during DNA damage response. We use a wide range of approaches, including molecular and structural biology, cell biology, mouse models, genomics, and bioinformatics, to achieve our scientific objectives.