Michael B. Kastan, M.D., Ph.D.

Michael B. Kastan, M.D., Ph.D. Executive Director, Duke Cancer Institute
Professor of Pharmacology and Cancer Biology
Professor of Pediatrics

Duke University School of Medicine
422 Seeley Mudd Building
Box 3813
Durham, NC 27710

Phone: 919-684-3052
E-mail:

Research Interests

Cellular responses to DNA damage and other stresses are important determinants of cell viability and mutagenesis and impact the development of a wide range of human diseases. The ability to modulate cellular responses to DNA damage and other stresses can impact cancer development, tumor responses to therapy, the organ toxicities of cancer treatments or accidental exposure to radiation or other DNA damaging agents, the development of cardiovascular disease, outcome (extent of organ damage) following heart attack or stroke, and the rate of progression of certain neurodegenerative disorders. The focus of the Kastan lab has long been related to elucidating molecular mechanisms involved in cellular responses to DNA damage and other stresses. This began with studies of changes in DNA methylation and chromatin structure/modification during the process of DNA excision repair (Cell, 1982) and continued with a series of major discoveries demonstrating that the p53 protein, the most commonly mutated gene in human cancer, plays a critical role in enabling mammalian cells to cope with DNA damage, in particular by controlling progression of cells from the G1 phase of the cell cycle into S-phase (Cancer Research, 1991; PNAS, 1992; Cell, 1992) and regulating apoptosis. In the subsequent 20 years since the discovery of this role for p53, the lab has continued efforts to elucidate molecular mechanisms involved in DNA damage, including cell cycle control, programmed cell death signaling, DNA repair mechanisms, DNA damage-induced signal transduction pathways, and more recently interfaces between cellular metabolism and stress signaling. This has included generating many seminal insights into the roles and mechanisms of action of the ATM protein kinase, including its role in signaling to p53 (Cell, 1992; Genes and Development, 1997; Science, 1998), identifying other ATM substrates involved in DNA damage signaling (Nature, 2000; Genes and Development, 2002, 2004), and elucidating the mechanism of ATM activation (Nature, 2003). In the past several years, the lab has identified a novel and unexpected mechanism involved in the stress-induction of p53, namely a stimulation of the translation of p53 mRNA and recent insights have been gained into the molecular controls of this translational increase (Cell, 2005; Molecular Cell, 2008; Genes and Development, 2010) that are leading to development of small molecules that have the potential to modulate p53 induction after stress and protect normal tissues from radiation, chemotherapy, or hypoxia-reperfusion injury. Recent ATM studies in the lab have focused on molecular controls of DNA double strand break repair (Nature Cell Biology, 2007), its role in insulin signaling, metabolic syndrome, and mitochondrial function (Nature Cell Biology, 2000; Cell Metabolism, 2006; unpublished studies), and the development of small molecule inhibitors to be used as clinical tumor radiosensitizers (Cancer Research, 2008; unpublished studies).

Representative Publications

Kastan MB, Onyekewere O, Sidransky D, Vogelstein B, and Craig RW. Participation of P53 protein in the cellular response to DNA damage. Cancer Res 51:6304-6311, 1991.

Kastan MB, Zhan Q, El-Deiry WS, Carrier F, Jacks T, Walsh WV, Plunkett BS, Vogelstein B, and Fornace AJ. Jr. A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia telangiectasia. Cell 71:587-597, 1992.

Hartwell LH and Kastan MB. Cell cycle control and cancer. Science 266:1821-1828, 1994.

Canman CE, Lim D-S, Cimprich KA, Taya Y, Tamai K, Sakaguchi K, Appella E, Kastan MB, and Siliciano JD. Activation of the ATM kinase by ionizing radiation and phosphorylation of p53. Science 281:1677-1679, 1998.

Lim D-S, Kim S-T, Xu B, Maser RS, Lin J, Petrini JHJ, and Kastan MB. ATM phosphorylates p95/nbs1 in an S-phase checkpoint pathway. Nature 404:613-617, 2000.

Bakkenist CJ and Kastan MB. DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature 421:499-506, 2003.

Kitagawa R, Bakkenist CJ, McKinnon PJ, and Kastan MB. Phosphorylation of SMC1 is a Critical Downstream Event in the ATM-NBS1-BRCA1 Pathway. Genes and Development 18:1423-1438, 2004.

Takagi M, Abasalon M, McLure KG, Kastan MB. Regulation of p53 Translation and Induction after DNA Damage by Ribosomal Protein L26 and Nucleolin. Cell 123: 49-63, 2005.

Berkovich E, Monnat R, Kastan MB. Roles of ATM and NBS1 in chromatin structure modulation and double strand break repair. Nature Cell Biology 9: 683-690, 2007.

Chen, J and Kastan, MB. 5' - 3' UTR Interactions Regulate p53 mRNA Translation and Provide a Target for Modulating p53 Induction After DNA Damage. Genes and Development 24: 2146-2156, 2010.


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