Eric J. Brown

faculty photo
Associate Professor of Cancer Biology
Member, Abramson Cancer Center
Fellow, Institute on Aging, University of Pennsylvania SOM
Member, Institute for Translational Medicine and Therapeutics, University of Pennsylvania SOM
Member, Penn Skin Disease Research Center
Member, Penn Institute for Regenerative Medicine
Associate Investigator, Abramson Family Cancer Research Institute
Director of Education, Abramson Family Cancer Research Institute
Department: Cancer Biology

Contact information
Abramson Family Cancer Research Institute
Department of Cancer Biology
Perelman School of Medicine
University of Pennsylvania
421 Curie Boulevard
Philadelphia, PA 19104-6160
Office: 215-746-2805
Fax: 215-573-2486
B.A. (Genetics)
University of California at Berkeley, 1989.
Ph.D. (Immunology)
Harvard University, 1996.
Post-Graduate Training
Research Assistant, Laboratory of Stephen Rosenthal, University of California at San Francisco, 1989-1991.
Postdoctoral Research Fellowship, Laboratory of David Baltimore, California Institute of Technology and Massachusetts Institute of Technology , 1996-2003.
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Description of Research Expertise

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.

Rotation Projects
Please contact Dr. Brown for information on potential rotation projects.

Lab personnel
Muzaffer Kassab, Research Associate
Rahul Mandal, Postdoctoral Researcher
Jasmine Peake, Postdoctoral Researcher
Konstantinos Tsingas, Research Assistant
Praveen Rodrigo, Research Assistant

Heather Birmingham, Administrative Assistant,

Selected Publications

Shastri N, Tsai Y-C, Hile S, Jordan D, Powell B, Chen J, Maloney D, Dose M, Lo Y, Anastassiadis T, Rivera O, Kim T, Shah S, Borole P, Asija K, Wang X, Smith KD, Finn D, Schug J, Casellas R, Yatsunyk LA, Eckert KA and Brown EJ : Genome-wide identification of structure-forming repeats as principal sites of fork collapse upon ATR inhibition. Molecular Cell 72: 222-238, 2018.

Kim H, George E, Ragland R, Rafial S, Zhang R, Krepler C, Morgan M, Drapkin R, Brown EJ and Simpkins F: Targeting ATR/CHK1 is more effective than PARPi alone in BRCA mutant models. Clinical Cancer Research 23: 3097-3108, 2017.

Anastassiadis T, Brown EJ: Wild-type RAS: Keeping mutant RAS in CHK. Cancer Cell 25(2): 137-8, 2014.

Ragland RL, Patel S, Rivard RS, Smith K, Peters AA, Bielinsky AK, Brown EJ: RNF4 and PLK1 are required for replication fork collapse in ATR-deficient cells. Genes & Development 27(20): 2259-73, 2013.

Schoppy DW, Ragland RL, Gilad O, Shastri N, Peters AA, Murga M, Fernandez-Capetillo O, Diehl JA, Brown EJ: Oncogenic stress sensitizes murine cancers to hypomorphic suppression of ATR. Journal of Clinical Investigation 122(1): 241-252, 2012.

Gilad, O., Nabet, B.L., Ragland, R.L., Schoppy, D.W., Smith, K.D., Durham, A.C., Brown, E.J: Combining ATR suppression with oncogenic Ras synergystically increases genomic instability, causing synthetic lethality or tumorigenesis in a dosage-dependent manner. Cancer Research 70(23): 9693-9702, 2010.

Ruzankina, Y., Schoppy, D.W., Asare, A., Clark, C.E., Vonderheide, R.H., Brown, E.J.: Tissue regenerative delays and synthetic lethality in adult mice upon combined deletion of ATR and p53. Nature Genetics 41(10): 1144-1149, 2009.

Chanoux, R.A., Yin, B., Urtishak, K.A., Bassing, C.H., Brown, E.J.: ATR and H2AX cooperate in maintaining genome stability under replication stress. The Journal of Biological Chemistry 284(9): 5994-6003, 2009.

Smith, K.D., Fu, M.A., Brown, E.J.: Tim-Tipin dysfunction creates an indispensible reliance on the ATR-Chk1 pathway for continued DNA synthesis. The Journal of Cell Biology 187(1): 15-23, 2009.

Ruzankina, Y., Pinzon-Guzman, C., Asare, A., Ong, T., Pontano, L., Cotsarelis, G., Zediak, V.P., Velez, M., Bhandoola, A., Brown, E.J.: 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.

Urtishak KA, Smith KD, Chanoux RA, Greenberg RA, Johnson FB, Brown EJ: Timeless maintains genomic stability and suppresses sister chromatid exchange during unperturbed DNA replication. The Journal of Biological Chemistry 284(13): 8777–85, 2009.

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Last updated: 10/16/2023
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