Philipp Oberdoerffer, Ph.D.

Philipp  Oberdoerffer, Ph.D.
Head, Epigenetics of DNA Repair and Aging Section

Our lab is interested in elucidating the crosstalk between DNA damage, chromatin and nuclear (dys)function. Extensive structural reorganization of DNA damage-proximal chromatin is critical to facilitate and control repair factor access. DNA damage has further been linked to epigenetic deregulation beyond the sites of damage. Together, these changes are thought to contribute to organismal decline and malignant transformation. Using molecular biology, animal models and genomics approaches, we seek to understand both (i) the role of chromatin (modifiers) in DNA repair and (ii) the functional consequences of damage-induced chromatin reorganization in vivo.

Areas of Expertise

1) chromatin, 2) DNA repair, 3) DNA double-strand breaks, 4) nuclear integrity, 5) sirtuins,
6) aging

Contact Info

Philipp Oberdoerffer, Ph.D.
Center for Cancer Research
National Cancer Institute
Building 41, Room B907
Bethesda, MD 20892
Ph: 240-760-6681

In the Epigenetics of DNA Repair and Aging Section (EDRA), we use a combination of mouse models and cell-based approaches to address fundamental questions related to the complex crosstalk between chromatin, DNA repair and cellular dysfunction, We are particularly interested in DNA double-strand break (DSB) repair via homologous recombination (HR), which plays a central role in the cellular response to replication stress – a major source of endogenous DNA damage that is tightly linked to both cellular senescence and cancer susceptibility.

Our lab has made significant advances in understanding the epigenetic consequences of DNA damage in vivo. Using a mouse model that allows for temporally and spatially defined DSB induction, we recently uncovered an unexpected capacity of primary cells to maintain transcriptome integrity in response to acute DSB exposure. By combining ChIP-Seq, transcriptome profiling and chromatin interactome data, we now aim to dissect the epigenetic impact of chronic DSB induction with unprecedented, three-dimensional resolution.

In an orthogonal approach, we have identified novel, chromatin-related mediators of DNA repair by HR using a focused RNA interference (RNAi). In so doing we found that the repressive macro-histone variant macroH2A1.2 can regulate HR by modulating DSB-proximal chromatin to promote BRCA1-dependent genome maintenance. Our ongoing studies suggest that macroH2A1.2 is also a critical, protective component of the replication stress response, with direct implications for cellular senescence and tumor growth. Of note, macroH2A1.2 represents one of two alternative splice variants of the macroH2A1 (H2AFY) gene, which have seemingly opposing roles during DNA repair and cell growth and are differentially expressed in a variety of human tumors. Analyses of unique macroH2A1 splice variant interactomes and features are ongoing.

NIH Scientific Focus Areas:
Cancer Biology, Cell Biology, Chromosome Biology, Genetics and Genomics, Molecular Biology and Biochemistry
View Dr. Oberdoerffer's PubMed Summary.

Selected Recent Publications

  1. Kim J, Sturgill D, Sebastian R, Khurana S, Tran AD, Edwards GB, Kruswick A, Burkett S, Hosogane EK, Hannon WW, Weyemi U, Bonner WM, Luger K, Oberdoerffer P.
    Mol Cell. 69(1): 36-47, 2017. [ Journal Article ]
  2. Kim J, Sturgill D, Tran AD, Sinclair DA, Oberdoerffer P.
    Nucleic Acids Res.. 44(7): e64, 2016. [ Journal Article ]
  3. Kim J, Sun C, Tran AD, Chin PJ, Ruiz PD, Wang K, Gibbons RJ, Gamble MJ, Liu Y, Oberdoerffer P.
    Nat Struct Mol Biol.. 26(3): 213-219, 2019. [ Journal Article ]
  4. Khurana S, Kruhlak MJ, Kim J, Tran AD, Liu J, Nyswaner K, Shi L, Jailwala P, Sung MH, Hakim O, Oberdoerffer P.
    Cell Rep.. 8(4): 1049-1062, 2014. [ Journal Article ]
  5. Liu J, Kruswick A, Dang H, Tran AD, Kwon SM, Wang XW, Oberdoerffer P.
    Nat Commun.. 8(1): 137, 2017. [ Journal Article ]

In 2004, Dr. Oberdoerffer obtained his Ph.D. in Genetics and Immunology under the supervision of Dr. Klaus Rajewsky at the University of Cologne, Germany. He then joined Dr. David Sinclair's group at Harvard Medical School, first as a National Space Biomedical Research Institute (NSBRI) Investigator, and later as a Leukemia and Lymphoma Society Special Fellow. In 2009, he joined the Mouse Cancer Genetics Program at the Center for Cancer Research, NCI where he studies the molecular link between DNA damage, chromatin and aging. In 2013, Dr. Oberdoerffer joined the Laboratory for Receptor Biology and Gene Expression at NCI.

Name Position
Robin Sebastian Ph.D. Postdoctoral Fellow (Visiting)
David M. Sturgill, Ph.D. Staff Scientist
Andy Tran Ph.D. Research Biologist