Robin Sebastian, PhD

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Assistant Professor

Research Program

Visualizing DNA damage (green) and DNA replication (purple)
Visualizing DNA damage (green) and DNA replication (purple)
Markers of genome instability: aneuploidy and lagging chromosome visualized during mitosis using chromosome painting
Markers of genome instability: aneuploidy and lagging chromosome visualized during mitosis using chromosome painting
Sequencing approaches to pinpoint damaged chromatin (𝛾H2AX ChIP-seq) and assess its effect on DNA replication (BrdU-seq)
Sequencing approaches to pinpoint damaged chromatin (𝛾H2AX ChIP-seq) and assess its effect on DNA replication (BrdU-seq)

Educational Background

  • PhD, Biochemistry, Indian Institute of Science, Bengaluru, India
  • MS, Biological Sciences, Indian Institute of Science, Bengaluru, India

Honors & Awards

  • Fellows Award for Research Excellence, NIH
  • National Cancer Institute Director’s Intramural Innovation Award
  • International Travel Award, Department of Biotechnology, Government of India

Research Interests

  • Cellular responses to DNA double-strand breaks during replication.
  • Roles of chromatin structure, nuclear architecture and protein modifications in response to replication stress and DNA damage.
  • Determinants of modular nature of mammalian DNA replication.

Lab Overview

The Sebastian lab is broadly focused on genome stability, with a particular emphasis on the cellular response to DNA replication stress and DNA double-strand breaks. We are interested in understanding how chromatin structure, nuclear architecture, protein modifications and epigenetic changes influence the replication and repair of the genome. Our work integrates functional genomics, advanced imaging, proteomics and classic biochemistry to uncover mechanisms that maintain genome integrity in cancer with the goal of targeting them for therapy. Current and future directions include exploring and characterizing novel mechanisms in genome maintenance and developing screens to identify and target new genome-protective factors in cancers with high replication stress.

Selected Publications

PubMed

Sebastian R, Sun EG, Fedkenheuer M, Fu H, Jung S, Thakur BL, Redon CE, Pegoraro G, Tran AD, Gross JM, Mosavarpour S, Kusi NA, Ray A, Dhall A, Pongor LS, Casellas R, Aladjem MI. Mechanism for local attenuation of DNA replication at double-strand breaks. Nature. 2025 Mar;639(8056):1084-1092. doi: 10.1038/s41586-024-08557-9. Epub 2025 Feb 19. PubMed PMID: 39972127.

Sebastian R, Aladjem MI, Oberdoerffer P. Encounters in Three Dimensions: How Nuclear Topology Shapes Genome Integrity. Front Genet.2021;12:746380. doi: 10.3389/fgene.2021.746380. eCollection 2021. Review. PubMed PMID: 34745220; PubMed Central PMCID: PMC8566435.

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. Mol Cell. 2020 Sep 3;79(5):836-845.e7. doi: 10.1016/j.molcel.2020.06.028. Epub 2020 Jul 9. PubMed PMID: 32649884; PubMed Central PMCID: PMC7483679.