Pathology & Laboratory Medicine

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Laboratory of Epigenetics and Immunity

Steven Z. Josefowicz, PhD, Principal Investigator

Signals are transmitted to chromatin to facilitate rapid, robust, and selective gene expression within the three billion base-pair genome in response to environmental cues, such as pathogen sensing. The goal of our ongoing research is to reveal mechanisms allowing for this scope and selectivity, and to understand them in the context of dynamic and fluid chromatin and all of its constituents (as a multi-molecular assembly or “biomolecular condensate”). Our recent studies of pathways that transmit extracellular signals to selectively induce gene expression establish the cooperative function of epigenetic mechanisms (histone modifications) and transcription factor activation and their coordinated regulation by chromatin-associated kinases. We are finding that these signaling-to-chromatin pathways are potent in regulation of enhancer activation and higher order chromatin architecture, both during the inflammatory process and in cancer. In ongoing and future work we extend these studies to understand how epigenetic processes provide an “evolutionary toolbox” for adaptations driven by spatiotemporal changes in gene expression. These studies have potential to synthesize an understanding of the extensive cooption of immune genes for non-immune processes (ex. thermogenesis, neuronal development), reveal novel mechanisms of adaptation, and explain inflammation- and age-associated pathologies.

Active Projects

  • Signaling to chromatin for dynamic regulation of chromatin architecture and transcription
  • Function of chromatin associated kinases in inflammation and cancer 
  • Epigenetic "scars" of chronic inflammation and accelerated aging in chronic HIV infection

Active Grants

  • Pathway to Independence Award: "Regulation of Chromatin by Histone Phosphorylation"
    PI: Steven Z. Josefowicz, Ph.D.
    National Institutes of Health (NIH)


Visit the Josefowicz Lab Webpage


Selected Publications

Chromatin Kinases Act on Transcription Factors and Histone Tails in Regulation of Inducible Transcription

Steven Josefowicz, PhD

Chromatin Kinases Act on Transcription Factors and Histone Tails in Regulation of Inducible Transcription

Mol Cell. 2016 Oct 20;64(2):347-361. 

Josefowicz SZ*, Shimada M*, Armache A, Li CH, Miller RM, Lin S, Yang A, Dill BD, Molina H, Park HS, Garcia BA, Taunton J, Roeder RG, Allis CD.

PMID: 27768872; PMCID: PMC5081221.

*equal contribution

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Greater Than the Sum of Parts: Complexity of the Dynamic Epigenome

Steven Josefowicz, PhD

Greater Than the Sum of Parts: Complexity of the Dynamic Epigenome

Mol Cell. 2016 Jun 2;62(5):681-94. 

Soshnev AA, Josefowicz SZ, Allis CD.

PMID: 27259201; PMCID: PMC4898265

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Mouse regulatory DNA landscapes reveal global principles of cis-regulatory evolution

Steven Josefowicz, PhD

Mouse regulatory DNA landscapes reveal global principles of cis-regulatory evolution

Science. 2014 Nov 21;346(6212):1007-12.

Vierstra J et al.*

PMID: 25411453; PMCID: PMC4337786

*Josefowicz SZ, as an ENCODE Consortium member

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Regulators of chromatin state and transcription in CD4 T-cell polarization

Steven Josefowicz, PhD

Regulators of chromatin state and transcription in CD4 T-cell polarization

Immunology. 2013 Jul;139(3):299-308. 

Josefowicz SZ.

PMID: 23590627; PMCID: PMC3701176

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Extrathymic generation of regulatory T cells in placental mammals mitigates maternal-fetal conflict

Steven Josefowicz, PhD

Extrathymic generation of regulatory T cells in placental mammals mitigates maternal-fetal conflict

Cell. 2012 Jul 6;150(1):29-38.

Samstein RM, Josefowicz SZ, Arvey A, Treuting PM, Rudensky AY. 

PMID: 22770213; PMCID: PMC3422629

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Weill Cornell Medicine Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464 Fax: (212) 746-8192