Jacob Stewart-Ornstein, Ph.D.

  • Assistant Professor
  • Department of Computational and Systems Biology

Education & Training

  • BAS, Biochemistry, McMaster University, Hamilton, Ontario, Canada-2007
  • Ph.D.,Biochemistry and Molecular Biology, University of California, San Francisco-2012
  • Postdoc,Cancer Biology and Systems Biology, Harvard Medical School, Boston, MA-2013-2018

Research Interest Summary

Experimental and computational approaches to study non-genetic control of DNA damage signaling.

Research Categories

Research Interests

Tissues in our body show a range of radiosensitivities. Analogously some cancers are extremely sensitive to DNA damage from chemotherapy or radiation and others are not. The DNA damage transcription factor p53 plays a role in specifying these differential sensitivities. We use models of different tissues to explore how DNA damage signaling varies. We study both signaling dynamics and differential DNA binding by transcription factors.  We also have a long-term interest in comparative DNA damage signaling between species.

Experimentally we focus on extending our understanding of p53 and DNA damage signaling with a rich set of measures of signaling dynamics and genomic aspects of DNA damage signaling.  We use RNA-, ATAC- and ChIP-seq to probe the global genomic landscape of DNA damage signaling across multiple cancer types.  We also continued to develop microscopy approaches for live and fixed multiplex single cell imaging to understand the full cellular state.  By interpreting this complex data through a rigorous model-based framework we aim to pinpoint the pathways and timepoints where drugging the system might be most effective.

Representative Publications

Stewart-Ornstein J, Weissman JS†, El-Samad H†. (2012) Cellular Noise Regulons Underlie Fluctuations in Saccharomyces cerevisiae. Molecular Cell 45:483-93.

Brandman O, Stewart-Ornstein J, Wong D, Larson A, Williams CC, Li GW, Zhou S, King D, Shen PS, Weibezahn J, Dunn JG, Rouskin S, Inada T, Frost A, Weissman JS. (2012) A ribosome-bound quality control complex triggers degradation of nascent peptides and signals translation stress.  Cell. 2012 151(5):1042-54.

Stewart-Ornstein J, Nelson C, DeRisi J, Weissman JS, and El-Samad H(2013). Msn2 coordinates a stoichiometric gene expression program..  Current Biol. 23(23):2336-45.

Lande-Diner L, Stewart-Ornstein J, Weitz CJ and Lahav G (2015). Single cell analysis of circadian dynamics in tissue explants. Mol. Bio. Of the Cell, 26(22):3940-5.

Stewart-Ornstein J, Lahav G (2016). Dynamics of CDKN1A in Single Cells Defined by an Endogenous Fluorescent Tagging Toolkit.  Cell Reports, 14(7):1800-11.

Stewart-Ornstein J, Chen S, Bhatnagar R, Weissman JS, El-Samad H (2017).  Model Guided Optogenetic Study of PKA Signaling In Budding Yeast.  Mol. Bio. Of the Cell, 28(1):221-227.

Stewart-Ornstein J, Lahav G (2017). p53 dynamics in response to DNA damage vary across cell lines and are shaped by efficiency of DNA repair and activity of the kinase ATM. Science Signaling 10(476).

Hafner A, Stewart-Ornstein J, Purvis J, Forester B, Lahav G† (2017). p53 pulses lead to distinct patterns of gene expression albeit similar DNA binding.  Nat. Struct. Mol. Biol. 24(10):840-847.

Stewart-Ornstein  J, Cheng J, and Lahav G(2017).  Conservation and Divergence of p53 Oscillation Dynamics across Species.  Cell Systems 5(4):410-417.

Hafner A, Kublo L, Lahav G, Stewart-Ornstein J (2019). Identification of universal and cell type specific p53 DNA binding.  Submitted; biorxiv doi: https://doi.org/10.1101/177667

Full List of Publications