Associate Professor
Radiation Oncology & Molecular Radiation Sciences Department, School of Medicine
RESEARCH OVERVIEW
My laboratory investigates the fundamental impact of epigenomic context on genome maintenance and its contribution to malignant transformation and overall cell function. Using a combination of molecular biology, imaging, genomics, cell-based approaches, and mouse models, we have uncovered a critical role for the splicing-regulated macroH2A1 histone variant in DSB repair pathway choice, fragile site integrity and telomere maintenance. Our ongoing research aims to 1) dissect the implications of macroH2A1 splice variant imbalance – and chromatin context more generally – for genome integrity, malignant transformation and tumor cell sensitivity to genotoxic agents; and 2) examine the contribution of a newly emerging aspect of chromatin structure, the modification of nuclear RNAs, to DNA repair and genome instability.
Cancer Biology | Cell Biology | Cellular Stress and Cell Signaling | Genetics, Genomics and Gene Regulation
Selected Publications:
Oberdoerffer P, Miller KM. Histone H2A variants: Diversifying chromatin to ensure genome integrity. Seminars in Cell & Developmental Biology, 2023.
Sebastian R, Hosogane EK, Sun EG, Tran AD, Reinhold WC, Burkett S, Sturgill DM, Gudla PR, Pommier Y, Aladjem MI, Oberdoerffer P. Epigenetic Regulation of DNA Repair Pathway Choice by MacroH2A1 Splice Variants Ensures Genome Stability. Molecular Cell, 2020.
Kim J, Sun C, Tran AD, Chin PJ, Ruiz PD, Wang K, Gibbons RJ, Gamble MJ, Liu Y*, Oberdoerffer P*. The macroH2A1.2 histone variant links ATRX loss to alternative telomere lengthening. Nature Structural and Molecular Biology, 2019. * Corresponding authors
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. Replication Stress Shapes a Protective Chromatin Environment across Fragile Genomic Regions. Molecular Cell, 2018.
Sebastian R, Oberdoerffer P. Transcription-associated events affecting genomic integrity. Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 2017.