Radiation Oncology & Molecular Radiation Sciences
Johns Hopkins University School of Medicine
Philipp Oberdoerffer, Ph. D.
Research Interests
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, their modifications and secondary structures.
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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, telomere maintenance and topological stress resposnes. 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.
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Adapted from Kustatscher et al., NSMB 2005
In addition to histones and chromatin modulators, non-coding RNAs, their modifications as well as RNA:DNA hybrid structures are emerging as an integral component of the epigenome. We hypothesize that these components provide temporal and spatial control of repair factor function and/or expression. We have completed several CRISPR/Cas9 screening efforts to identify novel RNA-based modulators of cancer cell sensitivity to DNA damaging agents and in-depth investigations of validated candidates are ongoing.
m6A RNA-modification accumulates at DSBs and on nuclear RNAs after DNA damage
