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Indiana University Bloomington

Heather O'HaganHeather O'Hagan

Assistant Professor, Medical and Molecular Genetics

Office: Jordan Hall 108

Phone: 812/ 855-3035

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Lab Website

Education

B.S., College of William and Mary, 1998
Ph.D., University of Michigan, 2004
Postdoctoral Fellow, Johns Hopkins University

Research

Inflammation and the associated increase in reactive oxygen species (ROS) play a key role in the initiation and progression of a majority of human epithelial cancers. Recent work by many groups has demonstrated that inflammation causes alterations in DNA methylation, microRNA expression, and, on a global level, histone marks. Since by definition these epigenetic changes are mitotically heritable and affect gene expression, they likely play a role in establishing disease phenotypes. During carcinogenesis, aberrant gains in promoter DNA methylation transcriptionally silence tumor suppressor genes, linking DNA methylation changes directly to tumorigenesis. However, it is unknown what the mechanisms of targeting and initiation are for these stable cancer-specific epigenetic marks. To begin to understand the mechanism of initiation of epigenetic changes, we used both in vitro and in vivo models to link oxidative DNA damage and inflammation to acute changes in the interaction of epigenetic silencing proteins with each other and the chromatin, suggesting that one role of oxidative damage in disease may be to initiate epigenetic changes. Current research in my lab further examines the relationship between oxidative damage, DNA repair, and epigenetic changes. We are using chromatin isolation, chromatin immunoprecipitation, and protein interaction experiments in the setting of knock down of the involved proteins to establish the connection between repair of oxidative damage and the recruitment of epigenetic silencing proteins to chromatin. As all the implicated epigenetic proteins can post-translationally modify other proteins, the lab is also interested in determining if protein modifications play a role in the interaction and/or function of these proteins at sites of DNA damage.

Representative Publications

Jeschke J, O'Hagan HM, Zhang W, Vatapalli R, Calmon MF, Danilova L, Nelkenbrecher C,
Van Neste L, Bijsmans IT, Van Engeland M, Gabrielson E, Schuebel KE, Winterpacht A, Baylin
SB, Herman JG, Ahuja N. Frequent inactivation of cysteine dioxygenase type 1 contributes to
survival of breast cancer cells and resistance to anthracyclines. Clin Cancer Res. 2013; 19(12):
3201-11.

O’Hagan HM*, Wang W*, Sen S, Shields CD, Lee SS, Zhang Y, Clements EG, Cai Y, Van
Neste L, Easwaran H, Casero RA, Sears CL, Baylin SB. (2011). Oxidative Damage Targets
Complexes Containing DNA Methyltransferases, SIRT1 and Polycomb Members to Promoter
CpG Islands. Cancer Cell. 20(5):606-19. *equal authorship

Mohammad HP, Cai Y, McGarvey KM, Easwaran H, Van Neste L, Ohm JE, O'Hagan HM,
Baylin SB. (2009). Polycomb CBX7 promotes initiation of heritable repression of genes
frequently silenced with cancer-specific DNA hypermethylation. Cancer Research. 69(15):6322-
30.

O'Hagan HM, Mohammad HP, Baylin SB. (2008). Double strand breaks can initiate gene
silencing and SIRT1-dependent onset of DNA methylation in an exogenous promoter CpG island.
PLoS Genetics. 4(8):e1000155.

Derheimer FA*, O’Hagan HM*, Krueger HM, Hanasoge S, Paulsen MT, Ljungman M.
(2007). RPA and ATR link transcriptional stress to p53. Proc Natl Acad Sci. 104(31):12778-83.
*equal authorship

O'Hagan HM and Ljungman M. (2004). Efficient NES-dependent protein nuclear export
requires ongoing synthesis and export of mRNAs. Experimental Cell Research. 297(2):548-59.

O'Hagan HM and Ljungman M. (2004). Nuclear accumulation of p53 following inhibition of
transcription is not due to diminished levels of MDM2. Oncogene. 23(32):5505-12.

Galigniana MD, Harrell JM, O'Hagan HM, Ljungman M, Pratt WB. (2004). Hsp90-binding
immunophilins link p53 to dynein during p53 transport to the nucleus. J Biol Chem. 279(21):
22483-9.

O'Hagan HM and Ljungman M. (2004). Phosphorylation and nuclear accumulation are
distinct events contributing to the activation of p53. Mutation Research. 546(1-2):7-15.
Heather M. O’Hagan, Ph.D. - CV Page 3

Ljungman M, O’Hagan HM, and TenBroeke MT. (2001). Induction of ser15 and lys382
modification of p53 blockage of transcription elongation. Oncogene. 20(42): 5964-71.

Kilbanov SA, O’Hagan HM, and Ljungman M. (2001). Accumulation of soluble and
nucleolar-associated p53 proteins following cellular stress. J. Cell Sci. 114:1867-1873.