Targeting transcriptional and epigenetic reprogramming in stromal cells in fibrosis and cancer

Nasun Hah, Mara H. Sherman, Ruth T. Yu, Michael Downes, Ronald M. Evans

Research output: Chapter in Book/Report/Conference proceedingConference contribution

7 Scopus citations

Abstract

The basis of many human diseases arises from both genetic and epigenetic regulation. Recent advances in the understanding of the mechanisms underlying transcriptional and epigenetic regulation and their prevalence as contributors to a diverse range of human diseases have led us to focus on transcription and epigenetic changes in a variety of human disease conditions. Specifically, our recent studies in liver fibrosis and pancreatic cancer have demonstrated that the epigenetic regulation in hepatic stellate cells (HSCs) and pancreatic stellate cells (PSCs) significantly contributes to the progress in such diseases and presents great therapeutic potential. We show that the vitamin D receptor (VDR) acts as a master genomic suppressor in both HSC and PSC activation. The studies also have demonstrated that the VDR ligand reduces fibrosis and inflammation in a murine liver fibrosis and pancreatitis model. Although our current studies focus on characterizing the roles of VDR and regulatory regions within gene promoters and regulatory enhancers, we have expanded our effort to epigenetic mechanisms as major determinants of gene activation and repression in order to develop potential therapeutics to modulate stroma-associated pathologies including inflammation, fibrosis, and cancer.

Original languageEnglish (US)
Title of host publication21st Century Genetics Genes at Work, 2015
EditorsTerri Grodzicker, Bruce Stillman, David Stewart
PublisherCold Spring Harbor Laboratory Press
Pages249-255
Number of pages7
ISBN (Print)9781621821472
DOIs
StatePublished - 2016
Event21st Century Genetics Genes at Work, 2015 - Huntington, United States
Duration: May 26 2015May 31 2015

Publication series

NameCold Spring Harbor Symposia on Quantitative Biology
Volume80
ISSN (Print)0091-7451
ISSN (Electronic)1943-4456

Other

Other21st Century Genetics Genes at Work, 2015
CountryUnited States
CityHuntington
Period5/26/155/31/15

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

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  • Cite this

    Hah, N., Sherman, M. H., Yu, R. T., Downes, M., & Evans, R. M. (2016). Targeting transcriptional and epigenetic reprogramming in stromal cells in fibrosis and cancer. In T. Grodzicker, B. Stillman, & D. Stewart (Eds.), 21st Century Genetics Genes at Work, 2015 (pp. 249-255). (Cold Spring Harbor Symposia on Quantitative Biology; Vol. 80). Cold Spring Harbor Laboratory Press. https://doi.org/10.1101/sqb.2015.80.027185