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MD, PhD, Biochemistry and Biophysics, UNC-Chapel Hill, Cancer Genetics

Sarah Graham Kenan Distinguished Professor, Biochemistry and Biophysics
UNC-Chapel Hill
Cancer Genetics

Area of Interest

DNA Repair

We are studying the molecular mechanism of nucleotide excision repair in humans. This is a general DNA repair system that repairs all base lesions including the carcinogenic lesions induced by the main environmental carcinogens sunlight and cigarette smoke. Our lab was the first to reconstitute the excision nuclease in a defined system. Our current work on excision repair aims to understand the structural and kinetic factors that enable the human excision nuclease to remove virtually infinite types of base lesions and to define the interconnections between DNA excision repair, the DNA damage checkpoints, and the circadian clock.

DNA Damage Checkpoints

DNA damage checkpoints are biochemical pathways that transiently block cell cycle progression while the DNA contains damage. Checkpoints prevent genomic instability, cancer, and death in multicellular organisms. The DNA damage checkpoints, like other signal transduction pathways, have four components: damage sensors, mediators, signal transducers and effectors. The goal of our research is to purify the human checkpoint proteins, characterize these proteins biochemically, and reconstitute the DNA damage checkpoint in vitro. We have already established an in vitro system that recapitulates some of the key features of the human DNA damage checkpoint response to base damage. Abnormal checkpoint response to DNA damage is a universal feature of cancers, and biochemical characterization of the checkpoint response should aid in developing new approaches to cancer chemotherapy.

Cryptochrome and Regulation of the Biological Clock

Circadian rhythm is the oscillation in physiology and behavior of organisms with approximately 24-hour periodicity. The circadian clock is synchronized to the daily solar cycle by light. We have discovered that a flavoprotein called cryptochrome, closely related to the light-dependent DNA repair enzyme photolyase, regulates the mammalian circadian clock by light-independent and light-dependent mechanisms. Currently, we are investigating the action mechanism of cryptochrome using biophysical methods including femtochemistry and biochemical methods. In addition, we are investigating the connection between the circadian cycle and DNA repair and how disruption of the circadian cycle might affect the susceptibility of mice and humans to cancers.

Awards and Honors

  • 2019 Hyman L. Battle Distinguished Cancer Research Award
  • 2016 North Carolina Award – the highest civilian honor given by the state
  • 2016 Carnegie Corporation’s Immigrant of the Year
  • 2016 Norma Berryhill Distinguished Lecturer
  • 2016 Jupiter Award for Outstanding Contributions to Science Education – Morehead Planetarium and Science Center
  • 2016 O. Max Gardner Award
  • 2016 ASBMB American Society for Biochemistry & Molecular Biology – Bert and Natalie Vallee Award
  • 2016 TACCI Turkish American Chamber of Commerce – Distinguished Service Award
  • 2016 TWESCO International Turkish Academy – Gold Medal at UN
  • 2016 Ugur Mumcu Memorial – Science Award
  • 2016 Lifetime Achievement Health Care Heroes – Triangle Business Journal
  • 2015 Nobel Prize in Chemistry
  • 2014 Distinguished Visiting Professor – Academia Sinica
  • 2009 Distinguished Alumni Award-University of Texas at Dallas
  • 2007 Koc Prize-Turkey
  • 2007 Honorary Coach of UNC Women’s Basketball Team
  • 2006 Honorary Doctorate, Bilkent University, Turkey
  • 2006 Member of the National Academy of Sciences, Turkey
  • 2005 Member of The National Academy of Sciences, USA
  • 2004 Fellow of The American Academy of Arts and Sciences

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Find publications on Pubmed