title: Targeting Transcriptional and Epigenetic Reprogramming in Stromal Cells in Fibrosis and Cancer.
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.
authors.affiliation: Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037.
authors.forename: Nasun
authors.initials: N
authors.lastname: Hah
authors.affiliation: Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037.
authors.forename: Mara H
authors.initials: MH
authors.lastname: Sherman
authors.affiliation: Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037.
authors.forename: Ruth T
authors.initials: RT
authors.lastname: Yu
authors.affiliation: Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037.
authors.forename: Michael
authors.initials: M
authors.lastname: Downes
authors.affiliation: Gene Expression Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037 Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, California 92037.
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Evans
mesh_terms: D000818:Animals; D065150:Cellular Reprogramming / Q000235:genetics*; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic; D005355:Fibrosis; D005786:Gene Expression Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D055166:Hepatic Stellate Cells / Q000378:metabolism*; D006801:Humans; D008103:Liver Cirrhosis / Q000235:genetics*; D051379:Mice; D009369:Neoplasms; D010190:Pancreatic Neoplasms / Q000235:genetics*; D058954:Pancreatic Stellate Cells / Q000378:metabolism*; D010195:Pancreatitis / Q000235:genetics; D018167:Receptors, Calcitriol / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism*
chemical_list: D018167:Receptors, Calcitriol