User:Kirsten3rd/Eric Jason Brown, Ph.D.

This is the bio page for Eric J. Brown, Ph.D.

California Institute of Technology: Postdoctoral research with David Baltimore Disrupted the ATR kinase in mice and studied the role of ATR in cell cycle checkpoints, genome stability, embryonic development and tumorigenesis. Harvard University: Ph.D. in Immunology with Stuart L. Schreiber (1996) Purified, cloned and performed structure/function analysis of mTOR University of California at Berkeley: B.A. in Genetics (1989)

Research Interests Maintenance of genome integrity plays a critical role in the prevention of cancer and other age-associated diseases. My laboratory studies the mechanisms utilized to safeguard the genome and investigates how failures in these processes impact tissue homoeostasis, cancer risk, and, potentially, cancer treatments. We are particularly interested in processes that maintain genome stability during DNA replication. 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. Thus, ATR pathway, as a component of a multilayered network of DNA replication and repair factors, performs an essential function in genome maintenance, acting to suppress both cancer and other age-associated diseases.

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

Lab personnel Yaroslava Ruzankina, Postdoctoral fellow Oren Gilad, Postdoctoral fellow Ryan Ragland, Postdoctoral fellow Kevin Smith, CAMB Graduate Student David Schoppy, CAMB Graduate Student Ashley Peters, Research Specialist PUBLICATIONS Y. Ruzankina, D. W. Schoppy, A. Asare, C. E. Clark, R. H. Vonderheide and E. J. Brown : Tissue regenerative delays and synthetic lethality in adult mice upon combined deletion of ATR and p53. Nat Genet 41: 1144-1149, 2009.

K. D. Smith, M. A. Fu and E. J. Brown : Tim-Tipin dysfunction creates an indispensible reliance on the ATR-Chk1 pathway for continued DNA synthesis. J Cell Biol 187: 15-23, 2009.

R. A. Chanoux, B. Yin, K. A. Urtishak, C. H. Bassing and E. J. Brown : ATR and H2AX cooperate in maintaining genome stability under replication stress. J Biol Chem 284: 5994-6003, 2009.

K. A. Urtishak, K. D. Smith, R. A. Chanoux, R. A. Greenberg, F. B. Johnson and E. J. Brown : Timeless maintains genomic stability in S phase and suppresses sister chromatid exchange. J Biol Chem 284: 8777–8785, 2009.

Y. Ruzankina, A. Asare and E. J. Brown : Replicative stress, stem cells and aging. Mech Ageing Dev 129: 460-466, 2008.

Y. Ruzankina, C. Pinzon-Guzman, A. Asare, T. Ong, L. Pontano, G. Cotsarelis, V. P. Zediak, M. Velez, A. Bhandoola and E. J. Brown: Deletion of the Developmentally Essential Gene ATR in Adult Mice Leads to Premature Aging Phenotypes and Stem Cell Loss. Cell Stem Cell 1: 113-126, 2007.

Y. Ruzankina and E. J. Brown : Relationships between stem cell exhaustion, tumour suppression and ageing. Br J Cancer 97: 1189-1193, 2007.

X. Guo, Y. Deng, Y. Lin, W. Cosme-Blanco , S. Chan , H. He, G. Yuan , E. J. Brown and S. Chang: Dysfunctional telomeres activate an ATM-ATR-dependent DNA damage response to suppress tumorigenesis. Embo J. 26: 4709-4719, 2007.

Gasser, S., Orsulic, S., Brown, EJ., Raulet, DH. : The DNA damage pathway regulates innate immune system ligands of the NKG2D receptor. Nature 436: 1186-1190, Aug 2005.

Brown, EJ., Baltimore, D.: Essential and dispensable roles of ATR in cell cycle arrest and genome maintenance. Genes Dev 17: 615-628, 2003.