National Academy of Sciences
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Election Year: 2003
Primary Section: 41, Medical Genetics, Hematology, and Oncology
Secondary Section: 26, Genetics
Membership Type: Member
I have studied the mechanism through which cells sense and respond to DNA damage and regulate the cell cycle. My lab uncovered a signal transduction pathway that is activated when DNA is broken or DNA polymerases are stalled. The generation of ssDNA is sensed and results in activation of a protein kinase cascade that activates gene expression and causes cell cycle arrest. This pathway is important for preventing cancer-causing mutations.
I also study how the cell cycle is regulated and discovered a family of Cdk inhibitors, CKIs, which organisms use to control cell proliferation during development and to prevent cancer. Through investigations of how CKIs are regulated, we discovered a modular pathway called the SCF through which proteins are marked for destruction. The SCF has a replaceable adaptor called an F-box protein that works like a socket wrench. When a particular F-box protein is in the SCF it recognizes one set of proteins to destroy, when another is present a different set is recognized. We have also worked to develop genetic cloning technologies to facilitate scientific progress. I believe that new technology drives science and generally has a much larger impact than individual basic science discoveries.