Philipp Oberdoerffer, PhD

Associate Professor of Radiation Oncology and Molecular Radiation Sciences
Department of Radiation Oncology
Division of Molecular Radiation Sciences
Radiation Oncology at Sibley Memorial Hospital

The Johns Hopkins University School of Medicine
1550 Orleans St
Baltimore, MD 21287
Tel:  410-614-9223
Fax:  410-502-2821
E-mail:  PO@jhmi.edu
Lab Website:  https://oberdoerfferp.wixsite.com/po-lab

TaeHee Lee

Postdoctoral fellow

Tongyu Wu

Masters Student, JHSPH

Xianzhen Zhou

Masters Student, JHSPH

Colina Qiao

Masters Student, JHSPH

Our lab investigates how epigenetic context affects genome maintenance pathways, and how this feature may be exploited to modulate cell function and malignant growth. We currently focus on:
(i) the crosstalk between chromatin composition and DNA repair outcome.
(ii) the modulation of DNA repair via chromatin-associated RNAs and their modifications.
​ The lab combines expertise in mouse genetics and molecular biology with imaging and epigenomics approaches to determine how DNA damage alters chromatin, gene expression and genome integrity in cell-based systems and mouse models. We have recently uncovered a prominent role for the splicing-regulated macro-histone variants macroH2A1.1 and macroH2A1.2 as effectors of DNA repair pathway choice, replication stress and telomere maintenance. Implications of macroH2A1 splice variant choice for replication integrity, malignant transformation and tumor cell sensitivity to genotoxic agents will be a major focus of our future research, particularly in the context of Homologous Recombination (HR) deficient cancers.

In addition to histones and chromatin modulators, non-coding RNAs and RNA:DNA hybrid structures are emerging as an integral component of the epigenome. We are interested in the mechanisms by which RNA modulates the DNA repair process. Our preliminary data suggest a link between nucleosome composition, replication stress and RNA:DNA hybrid formation, which we are eager to pursue. Moreover, we and others recently identified a role N6-methyladenosine (m6A)-modified RNA methyltransferase in HR and hypothesize that m6A-modified RNA may provide temporal and spatial control of repair factor function and/or expression, thereby contributing to genome maintenance and malignant transformation.

m6A RNA-modification accumulates at DSBs and on nuclear RNAs after DNA damage

Complete List of Published Work in MyBibliography
https://www.ncbi.nlm.nih.gov/myncbi/philipp.oberdoerffer.2/bibliography/public/

Histone H2A variants: Diversifying chromatin to ensure genome integrity. Oberdoerffer P, Miller KM.Semin Cell Dev Biol. 2022 Mar 21:S1084-9521(22)00078-7. doi: 10.1016/j.semcdb.2022.03.011. Online ahead of print.PMID: 35331626 Review.

Encounters in Three Dimensions: How Nuclear Topology Shapes Genome Integrity. Sebastian R, Aladjem MI, Oberdoerffer P.Front Genet. 2021 Oct 21;12:746380. doi: 10.3389/fgene.2021.746380. eCollection 2021.PMID: 34745220 Free PMC article. Review.

RNA: a double-edged sword in genome maintenance. Zong D, Oberdoerffer P, Batista PJ, Nussenzweig A.Nat Rev Genet. 2020 Nov;21(11):651-670. doi: 10.1038/s41576-020-0263-7. Epub 2020 Aug 6.PMID: 32764716 Review.

Epigenetic Regulation of DNA Repair Pathway Choice by MacroH2A1 Splice Variants Ensures Genome Stability. Sebastian R, Hosogane EK, Sun EG, Tran AD, Reinhold WC, Burkett S, Sturgill DM, Gudla PR, Pommier Y, Aladjem MI, Oberdoerffer P.Mol Cell. 2020 Sep 3;79(5):836-845.e7. doi: 10.1016/j.molcel.2020.06.028. Epub 2020 Jul 9.

The macroH2A1.2 histone variant links ATRX loss to alternative telomere lengthening. Kim J, Sun C, Tran AD, Chin PJ, Ruiz PD, Wang K, Gibbons RJ, Gamble MJ, Liu Y, Oberdoerffer P.Nat Struct Mol Biol. 2019 Mar;26(3):213-219. doi: 10.1038/s41594-019-0192-3. Epub 2019 Mar 4.PMID: 30833786 Free PMC article.