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dc.contributor.authorBradner, James Elliott
dc.contributor.authorMak, Raymond Heungwing
dc.contributor.authorTanguturi, Shyam Kumar
dc.contributor.authorMazitschek, Ralph
dc.contributor.authorHaggarty, Stephen John
dc.contributor.authorRoss, Kenneth N
dc.contributor.authorChang, Cindy Y.
dc.contributor.authorBosco, Jocelyn
dc.contributor.authorWest, Nathan
dc.contributor.authorMorse, Elizabeth
dc.contributor.authorLin, Katherine
dc.contributor.authorShen, John Paul
dc.contributor.authorKwiatkowski, Nicholas Paul
dc.contributor.authorGheldof, Nele
dc.contributor.authorDekker, Job
dc.contributor.authorDeAngelo, Daniel J.
dc.contributor.authorCarr, Steven A.
dc.contributor.authorSchreiber, Stuart L.
dc.contributor.authorGolub, Todd Robert
dc.contributor.authorEbert, Benjamin L.
dc.date.accessioned2016-11-16T20:54:08Z
dc.date.issued2010
dc.identifier.citationBradner, James E., Raymond Mak, Shyam K. Tanguturi, Ralph Mazitschek, Stephen J. Haggarty, Kenneth Ross, Cindy Y. Chang, et al. 2010. “Chemical Genetic Strategy Identifies Histone Deacetylase 1 (HDAC1) and HDAC2 as Therapeutic Targets in Sickle Cell Disease.” Proceedings of the National Academy of Sciences 107 (28) (June 28): 12617–12622. doi:10.1073/pnas.1006774107.en_US
dc.identifier.issn0027-8424en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:29400932
dc.description.abstractThe worldwide burden of sickle cell disease is enormous, with over 200,000 infants born with the disease each year in Africa alone. Induction of fetal hemoglobin is a validated strategy to improve symptoms and complications of this disease. The development of targeted therapies has been limited by the absence of discrete druggable targets. We developed a unique bead-based strategy for the identification of inducers of fetal hemoglobin transcripts in primary human erythroid cells. A small-molecule screen of bioactive compounds identified remarkable class-associated activity among histone deacetylase (HDAC) inhibitors. Using a chemical genetic strategy combining focused libraries of biased chemical probes and reverse genetics by RNA interference, we have identified HDAC1 and HDAC2 as molecular targets mediating fetal hemoglobin induction. Our findings suggest the potential of isoform-selective inhibitors of HDAC1 and HDAC2 for the treatment of sickle cell disease.en_US
dc.language.isoen_USen_US
dc.publisherProceedings of the National Academy of Sciencesen_US
dc.relation.isversionofdoi:10.1073/pnas.1006774107en_US
dc.relation.hasversionhttps://www.ncbi.nlm.nih.gov/pubmed/20616024en_US
dash.licenseLAA
dc.subjectHistoneen_US
dc.subjectAcetylationen_US
dc.subjectHomoglobinopathiesen_US
dc.subjectChromatinen_US
dc.titleChemical genetic strategy identifies histone deacetylase 1 (HDAC1) and HDAC2 as therapeutic targets in sickle cell diseaseen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalProceedings of the National Academy of Sciencesen_US
dash.depositing.authorMak, Raymond Heungwing
dc.date.available2016-11-16T20:54:08Z
dc.identifier.doi10.1073/pnas.1006774107*
dash.authorsorderedfalse
dash.contributor.affiliatedRoss, Kenneth
dash.contributor.affiliatedMazitschek, Ralph
dash.contributor.affiliatedSchreiber, Stuart
dash.contributor.affiliatedHaggarty, Stephen
dash.contributor.affiliatedKwiatkowski, Nicholas
dash.contributor.affiliatedTanguturi, Shyam
dash.contributor.affiliatedMak, Raymond
dash.contributor.affiliatedGolub, Todd
dash.contributor.affiliatedDeAngelo, Daniel
dash.contributor.affiliatedEbert, Benjamin
dash.contributor.affiliatedBradner, James E


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