Research Interests
Mechanisms that maintain genome stability during DNA replication and their importance in cancer treatment and aging.

Key words: DNA damage checkpoints, DNA repair, ATR, CHK1, replication fork stability, genome integrity, cancer and aging.

Description of Research

Maintaining the genome integrity delays the onset of cancer and other age-associated diseases. The processes that safeguard the genome are particularly important during DNA replication, when the normally stable DNA duplex structure is rendered susceptible to recombination events and collapse. My laboratory studies how genome integrity is maintained during DNA replication and investigates how defects in these mechanisms impact age-associated diseases, and cancer risk and treatment.

As an essential sensor of problems occurring during DNA replication, the ATR protein kinase regulates a signal transduction cascade that preserves troubled DNA replication forks and prevents their collapse into DNA double strand breaks. The conditions that activate the ATR pathway during DNA replication include oncogenic stress, replisome dysfunction, and encounters with difficult-to-replicate DNA sequences and naturally occurring forms of DNA damage. In aggregate, such problems are relatively common, particularly in cancers. Thus, ATR pathway, performs an essential function in genome maintenance that influences the emergence of cancer, cancer treatment and other age-associated diseases. Using proteomic and genomic approaches systems, we are investigating how the ATR pathway counters replicative stress at the replication fork and throughout the genome. In addition, we are investigating the use of ATR inhibitors as cancer treatments by identifying biomarkers of sensitivity as well as novel targets for combination drug treatments.