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Stuart H. Orkin, MD


Pediatric Hematology/Oncology

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Physician

  • Professor of Pediatrics, Harvard Medical School

Clinical Interests

  • Pediatric hematology/oncology

Contact Information

  • Office Phone Number617-355-7910
  • Fax617-632-4367

Bio

Dr. Orkin received his MD in 1972 from Harvard Medical School, followed by postdoctoral research at the National Institutes of Health and clinical training in pediatrics and hematology-oncology at Children's Hospital Boston and DFCI, where he joined the faculty in 1978. Dr. Orkin is a Howard Hughes Medical Institute Investigator and was elected to the 2019-2020 Council of the National Academy of Medicine. Over the past decade, his laboratory has defined critical nuclear regulators of hematopoiesis.

Fellowship:

  • Boston Children's Hospital, Pediatric Hematology/Oncology

Residency:

  • Boston Children's Hospital, Pediatrics

Medical School:

  • Harvard Medical School

Recent Awards:

  • Gruber Genetics Prize, Yale, 2021
  • Tobias Lecture Award, ISSCR, 2021
  • Harrington Prize for Innovation in Medicine, Harrington Discovery Institute and The American Society for Clinical Investigation, 2020
  • King Faisal Prize for Medicine, 2020
  • AAMC Award for Distinguished Research in Medical Sciences, 2005
  • Warren Alpert Foundation Prize, 1993
  • Member, Institute of Medicine, 1992
  • Member, American Academy of Arts and Sciences, 1992
  • Member, National Academy of Sciences, 1991
  • Dameshek Award, American Society of Hematology, 1986

Research

Molecular Genetics of Blood Cell Development and Stem Cells

All blood cells arise from committed progenitors, which are descendants of pluripotent hematopoietic stem cells. The goal of our laboratory is to understand how commitment to specific blood lineages is programmed and how cell-specific patterns of gene expression are established. Since gene expression is controlled by nuclear regulatory factors (transcription factors), efforts have centered on identifying those crucial for the development of stem cells or individual lineages. Research encompasses conventional molecular biology and contemporary mouse genetics.Lineage specification and hematopoietic differentiationRed blood cells and megakaryocytes (which produce platelets) share a common precursor cell. We discovered a transcription factor, GATA1, that participates in the regulation of virtually all red cell (erythroid) and megakaryocyte-specific expressed genes. Expression of GATA1 in progenitors drives cells toward erythroid and megakaryocytic fates. Disruption of the Gata1 gene in mice leads to a failure of maturation of both lineages. In addition to controlling end-stage markers of these lineages, GATA1 influences proliferation and cell death decisions of precursor cells. Using this mouse model to dissect mechanisms of cell differentiation, we have sought to understand how GATA1 functions in transcription. This line of investigation led us to hypothesize and then discover a cofactor required for GATA1's function in these lineages. This novel cofactor, FOG (for friend of GATA1), is also essential for normal red blood cell and megakaryocyte development. Current research focuses on how FOG modulates the function of GATA1 and related factors during hematopoietic and nonhematopoietic cell development.Hematopoiesis-leukemia interfaceRemarkably, many genes essential for normal hematopoietic development are involved in chromosomal translocations in human leukemias. This finding reflects perturbation of normal homeostasis by expression of an altered protein or excessive production of an otherwise normal factor. We are studying several transcription factors (e.g., SCL/tal-1, TEL) affected by genetic events in leukemias. Our work is directed toward understanding the normal roles of these transcription factors in hematopoiesis and vascular development. In addition, efforts are ongoing to recreate in mice the common form of childhood leukemia, acute lymphoblastic leukemia, associated with fusion of the TEL and AML1 genes. This animal model will permit improved understanding of the pathogenesis of acute lymphoblastic leukemia and provide a system for testing new therapies.

Indispensable epigenetic control of thymic epithelial cell development and function by polycomb repressive complex 2. Nat Commun. 2021 06 24; 12(1):3933.
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Author Correction: Transcription factor competition at the ?-globin promoters controls hemoglobin switching. Nat Genet. 2021 Apr; 53(4):586.
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Transcription factor competition at the ?-globin promoters controls hemoglobin switching. Nat Genet. 2021 04; 53(4):511-520.
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MOLECULAR MEDICINE: Found in Translation. Med (N Y). 2021 Feb 12; 2(2):122-136.
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ARID4B is critical for mouse embryonic stem cell differentiation towards mesoderm and endoderm, linking epigenetics to pluripotency exit. J Biol Chem. 2020 12 18; 295(51):17738-17751.
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Arid4b is critical for mouse embryonic stem cell differentiation towards mesoderm and endoderm, linking epigenetics to pluripotency exit. J Biol Chem. 2020 Oct 15.
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A saturating mutagenesis CRISPR-Cas9-mediated functional genomic screen identifies cis- and trans-regulatory elements of Oct4 in murine ESCs. J Biol Chem. 2020 11 20; 295(47):15797-15809.
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Enhancer dependence of cell-type-specific gene expression increases with developmental age. Proc Natl Acad Sci U S A. 2020 09 01; 117(35):21450-21458.
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An Engineered CRISPR-Cas9 Mouse Line for Simultaneous Readout of Lineage Histories and Gene Expression Profiles in Single Cells. Cell. 2020 Jun 25; 181(7):1693-1694.
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An Engineered CRISPR-Cas9 Mouse Line for Simultaneous Readout of Lineage Histories and Gene Expression Profiles in Single Cells. Cell. 2020 06 11; 181(6):1410-1422.e27.
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Multiplexed capture of spatial configuration and temporal dynamics of locus-specific 3D chromatin by biotinylated dCas9. Genome Biol. 2020 03 05; 21(1):59.
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Live-animal imaging of native haematopoietic stem and progenitor cells. Nature. 2020 02; 578(7794):278-283.
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Control of human hemoglobin switching by LIN28B-mediated regulation of BCL11A translation. Nat Genet. 2020 02; 52(2):138-145.
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CUT&RUNTools: a flexible pipeline for CUT&RUN processing and footprint analysis. Genome Biol. 2019 09 09; 20(1):192.
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BORIS promotes chromatin regulatory interactions in treatment-resistant cancer cells. Nature. 2019 08; 572(7771):676-680.
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Rational targeting of a NuRD subcomplex guided by comprehensive in situ mutagenesis. Nat Genet. 2019 07; 51(7):1149-1159.
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TAF5L and TAF6L Maintain Self-Renewal of Embryonic Stem Cells via the MYC Regulatory Network. Mol Cell. 2019 06 20; 74(6):1148-1163.e7.
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Extensive Recovery of Embryonic Enhancer and Gene Memory Stored in Hypomethylated Enhancer DNA. Mol Cell. 2019 05 02; 74(3):542-554.e5.
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Yap1 safeguards mouse embryonic stem cells from excessive apoptosis during differentiation. Elife. 2018 12 18; 7.
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Single-Cell Analysis Identifies LY6D as a Marker Linking Castration-Resistant Prostate Luminal Cells to Prostate Progenitors and Cancer. Cell Rep. 2018 12 18; 25(12):3504-3518.e6.
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CRISPR-SURF: discovering regulatory elements by deconvolution of CRISPR tiling screen data. Nat Methods. 2018 12; 15(12):992-993.
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PRC2 loss induces chemoresistance by repressing apoptosis in T cell acute lymphoblastic leukemia. J Exp Med. 2018 12 03; 215(12):3094-3114.
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FAM210B is an erythropoietin target and regulates erythroid heme synthesis by controlling mitochondrial iron import and ferrochelatase activity. J Biol Chem. 2018 12 21; 293(51):19797-19811.
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Emerging Genetic Therapy for Sickle Cell Disease. Annu Rev Med. 2019 01 27; 70:257-271.
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Polycomb Repressive Complex 2 is essential for development and maintenance of a functional TEC compartment. Sci Rep. 2018 09 25; 8(1):14335.
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Canonical PRC2 function is essential for mammary gland development and affects chromatin compaction in mammary organoids. PLoS Biol. 2018 08; 16(8):e2004986.
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Author Correction: High-fat diet enhances stemness and tumorigenicity of intestinal progenitors. Nature. 2018 08; 560(7717):E26.
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Downregulation of Endothelin Receptor B Contributes to Defective B Cell Lymphopoiesis in Trisomy 21 Pluripotent Stem Cells. Sci Rep. 2018 05 22; 8(1):8001.
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Mapping the Mouse Cell Atlas by Microwell-Seq. Cell. 2018 05 17; 173(5):1307.
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The Polycomb-Dependent Epigenome Controls ß Cell Dysfunction, Dedifferentiation, and Diabetes. Cell Metab. 2018 Jun 05; 27(6):1294-1308.e7.
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14q32 and let-7 microRNAs regulate transcriptional networks in fetal and adult human erythroblasts. Hum Mol Genet. 2018 04 15; 27(8):1411-1420.
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Integrated design, execution, and analysis of arrayed and pooled CRISPR genome-editing experiments. Nat Protoc. 2018 05; 13(5):946-986.
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Direct Promoter Repression by BCL11A Controls the Fetal to Adult Hemoglobin Switch. Cell. 2018 04 05; 173(2):430-442.e17.
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Dissecting super-enhancer hierarchy based on chromatin interactions. Nat Commun. 2018 03 05; 9(1):943.
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Mapping the Mouse Cell Atlas by Microwell-Seq. Cell. 2018 02 22; 172(5):1091-1107.e17.
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Genome-wide CRISPR-Cas9 Screen Identifies Leukemia-Specific Dependence on a Pre-mRNA Metabolic Pathway Regulated by DCPS. Cancer Cell. 2018 03 12; 33(3):386-400.e5.
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Regulation of embryonic haematopoietic multipotency by EZH1. Nature. 2018 01 25; 553(7689):506-510.
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Human genetic variation alters CRISPR-Cas9 on- and off-targeting specificity at therapeutically implicated loci. Proc Natl Acad Sci U S A. 2017 12 26; 114(52):E11257-E11266.
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Recent progress in understanding and manipulating haemoglobin switching for the haemoglobinopathies. Br J Haematol. 2018 03; 180(5):630-643.
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First critical repressive H3K27me3 marks in embryonic stem cells identified using designed protein inhibitor. Proc Natl Acad Sci U S A. 2017 09 19; 114(38):10125-10130.
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PRMT1-Mediated Translation Regulation Is a Crucial Vulnerability of Cancer. Cancer Res. 2017 09 01; 77(17):4613-4625.
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Gene correction of HAX1 reversed Kostmann disease phenotype in patient-specific induced pluripotent stem cells. Blood Adv. 2017 Jun 13; 1(14):903-914.
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A molecular roadmap for induced multi-lineage trans-differentiation of fibroblasts by chemical combinations. Cell Res. 2017 06; 27(6):843.
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A molecular roadmap for induced multi-lineage trans-differentiation of fibroblasts by chemical combinations. Cell Res. 2017 06; 27(6):842.
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The 2017 ASPHO distinguished career award goes to Holcombe E. Grier, MD. Pediatr Blood Cancer. 2017 06; 64 Suppl 1.
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Erythropoietin signaling regulates heme biosynthesis. Elife. 2017 05 29; 6.
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Challenges and emerging directions in single-cell analysis. Genome Biol. 2017 05 08; 18(1):84.
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Reduced Erg Dosage Impairs Survival of Hematopoietic Stem and Progenitor Cells. Stem Cells. 2017 07; 35(7):1773-1785.
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EED orchestration of heart maturation through interaction with HDACs is H3K27me3-independent. Elife. 2017 04 10; 6.
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Functional interrogation of non-coding DNA through CRISPR genome editing. Methods. 2017 05 15; 121-122:118-129.
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Transcription control by the ENL YEATS domain in acute leukaemia. Nature. 2017 03 09; 543(7644):270-274.
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Variant-aware saturating mutagenesis using multiple Cas9 nucleases identifies regulatory elements at trait-associated loci. Nat Genet. 2017 Apr; 49(4):625-634.
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Characterization of genomic deletion efficiency mediated by clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 nuclease system in mammalian cells. J Biol Chem. 2017 02 10; 292(6):2556.
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A molecular roadmap for induced multi-lineage trans-differentiation of fibroblasts by chemical combinations. Cell Res. 2017 03; 27(3):386-401.
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The histone demethylase UTX regulates the lineage-specific epigenetic program of invariant natural killer T cells. Nat Immunol. 2017 02; 18(2):184-195.
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Strict in vivo specificity of the Bcl11a erythroid enhancer. Blood. 2016 11 10; 128(19):2338-2342.
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CellMapper: rapid and accurate inference of gene expression in difficult-to-isolate cell types. Genome Biol. 2016 09 29; 17(1):201.
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Bcl11a Deficiency Leads to Hematopoietic Stem Cell Defects with an Aging-like Phenotype. Cell Rep. 2016 09 20; 16(12):3181-3194.
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Chronic Myelogenous Leukemia- Initiating Cells Require Polycomb Group Protein EZH2. Cancer Discov. 2016 11; 6(11):1237-1247.
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Lineage-specific BCL11A knockdown circumvents toxicities and reverses sickle phenotype. J Clin Invest. 2016 10 03; 126(10):3868-3878.
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Single-Cell Transcript Profiles Reveal Multilineage Priming in Early Progenitors Derived from Lgr5(+) Intestinal Stem Cells. Cell Rep. 2016 08 23; 16(8):2053-2060.
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Mathematical modeling of erythrocyte chimerism informs genetic intervention strategies for sickle cell disease. Am J Hematol. 2016 09; 91(9):931-7.
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Analyzing CRISPR genome-editing experiments with CRISPResso. Nat Biotechnol. 2016 07 12; 34(7):695-7.
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The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice. Cancer Cell. 2016 07 11; 30(1):183.
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Loss of Ezh2 synergizes with JAK2-V617F in initiating myeloproliferative neoplasms and promoting myelofibrosis. J Exp Med. 2016 07 25; 213(8):1479-96.
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Adenosine-to-inosine RNA editing by ADAR1 is essential for normal murine erythropoiesis. Exp Hematol. 2016 10; 44(10):947-63.
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An Achilles' Heel for MLL-Rearranged Leukemias: Writers and Readers of H3 Lysine 36 Dimethylation. Cancer Discov. 2016 07; 6(7):700-2.
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Hemoglobin genetics: recent contributions of GWAS and gene editing. Hum Mol Genet. 2016 10 01; 25(R2):R99-R105.
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Polycomb repressive complex 2 regulates skeletal growth by suppressing Wnt and TGF-ß signalling. Nat Commun. 2016 06 22; 7:12047.
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MEDICINE. Paying for future success in gene therapy. Science. 2016 May 27; 352(6289):1059-61.
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Acquired Tissue-Specific Promoter Bivalency Is a Basis for PRC2 Necessity in Adult Cells. Cell. 2016 Jun 02; 165(6):1389-1400.
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Corrigendum: LSD1 is essential for oocyte meiotic progression by regulating CDC25B expression in mice. Nat Commun. 2016 Apr 20; 7:11467.
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Interferon-a signaling promotes embryonic HSC maturation. Blood. 2016 07 14; 128(2):204-16.
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The Public Repository of Xenografts Enables Discovery and Randomized Phase II-like Trials in Mice. Cancer Cell. 2016 04 11; 29(4):574-586.
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Customizing the genome as therapy for the ß-hemoglobinopathies. Blood. 2016 05 26; 127(21):2536-45.
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High-fat diet enhances stemness and tumorigenicity of intestinal progenitors. Nature. 2016 Mar 03; 531(7592):53-8.
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Ezh2 Controls an Early Hematopoietic Program and Growth and Survival Signaling in Early T Cell Precursor Acute Lymphoblastic Leukemia. Cell Rep. 2016 Mar 01; 14(8):1953-65.
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Recent advances in globin research using genome-wide association studies and gene editing. Ann N Y Acad Sci. 2016 03; 1368(1):5-10.
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Serum-Based Culture Conditions Provoke Gene Expression Variability in Mouse Embryonic Stem Cells as Revealed by Single-Cell Analysis. Cell Rep. 2016 Feb 02; 14(4):956-965.
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Transcription factors LRF and BCL11A independently repress expression of fetal hemoglobin. Science. 2016 Jan 15; 351(6270):285-9.
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Genetic treatment of a molecular disorder: gene therapy approaches to sickle cell disease. Blood. 2016 Feb 18; 127(7):839-48.
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Polycomb Repressive Complex 2 Is a Barrier to KRAS-Driven Inflammation and Epithelial-Mesenchymal Transition in Non-Small-Cell Lung Cancer. Cancer Cell. 2016 Jan 11; 29(1):17-31.
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Dynamic Control of Enhancer Repertoires Drives Lineage and Stage-Specific Transcription during Hematopoiesis. Dev Cell. 2016 Jan 11; 36(1):9-23.
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Corrigendum: Failure to replicate the STAP cell phenomenon. Nature. 2016 Mar 17; 531(7594):400.
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Ezh2 regulates differentiation and function of natural killer cells through histone methyltransferase activity. Proc Natl Acad Sci U S A. 2015 Dec 29; 112(52):15988-93.
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LSD1 is essential for oocyte meiotic progression by regulating CDC25B expression in mice. Nat Commun. 2015 Dec 02; 6:10116.
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SWI/SNF-mutant cancers depend on catalytic and non-catalytic activity of EZH2. Nat Med. 2015 Dec; 21(12):1491-6.
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The LSD1 Family of Histone Demethylases and the Pumilio Posttranscriptional Repressor Function in a Complex Regulatory Feedback Loop. Mol Cell Biol. 2015 Dec; 35(24):4199-211.
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Failure to replicate the STAP cell phenomenon. Nature. 2015 Sep 24; 525(7570):E6-9.
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Hematopoietic stem cells develop in the absence of endothelial cadherin 5 expression. Blood. 2015 Dec 24; 126(26):2811-20.
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BCL11A enhancer dissection by Cas9-mediated in situ saturating mutagenesis. Nature. 2015 Nov 12; 527(7577):192-7.
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Hemoglobin switching's surprise: the versatile transcription factor BCL11A is a master repressor of fetal hemoglobin. Curr Opin Genet Dev. 2015 Aug; 33:62-70.
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Functional footprinting of regulatory DNA. Nat Methods. 2015 Oct; 12(10):927-30.
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EHMT1 and EHMT2 inhibition induces fetal hemoglobin expression. Blood. 2015 Oct 15; 126(16):1930-9.
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PRC2 Is Required to Maintain Expression of the Maternal Gtl2-Rian-Mirg Locus by Preventing De Novo DNA Methylation in Mouse Embryonic Stem Cells. Cell Rep. 2015 Sep 01; 12(9):1456-70.
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Inactivation of Eed impedes MLL-AF9-mediated leukemogenesis through Cdkn2a-dependent and Cdkn2a-independent mechanisms in a murine model. Exp Hematol. 2015 Nov; 43(11):930-935.e6.
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miRNA-embedded shRNAs for Lineage-specific BCL11A Knockdown and Hemoglobin F Induction. Mol Ther. 2015 Sep; 23(9):1465-74.
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Regulation of Peripheral Nerve Myelin Maintenance by Gene Repression through Polycomb Repressive Complex 2. J Neurosci. 2015 Jun 03; 35(22):8640-52.
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Embryonic stem cells as sources of donor-independent platelets. J Clin Invest. 2015 Jun; 125(6):2261-3.
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BCL11A deletions result in fetal hemoglobin persistence and neurodevelopmental alterations. J Clin Invest. 2015 Jun; 125(6):2363-8.
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Opposing Roles for the lncRNA Haunt and Its Genomic Locus in Regulating HOXA Gene Activation during Embryonic Stem Cell Differentiation. Cell Stem Cell. 2015 May 07; 16(5):504-16.
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The mTORC1/4E-BP pathway coordinates hemoglobin production with L-leucine availability. Sci Signal. 2015 Apr 14; 8(372):ra34.
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Flow-induced protein kinase A-CREB pathway acts via BMP signaling to promote HSC emergence. J Exp Med. 2015 May 04; 212(5):633-48.
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2014 William Allan Award: A hematologist's pursuit of hemoglobin genetics. Am J Hum Genet. 2015 Mar 05; 96(3):354-60.
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Angiopoietin-like proteins stimulate HSPC development through interaction with notch receptor signaling. Elife. 2015 Feb 25; 4.
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Functional Proteomic Analysis of Repressive Histone Methyltransferase Complexes Reveals ZNF518B as a G9A Regulator. Mol Cell Proteomics. 2015 Jun; 14(6):1435-46.
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Developmental control of polycomb subunit composition by GATA factors mediates a switch to non-canonical functions. Mol Cell. 2015 Jan 22; 57(2):304-316.
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Scl binds to primed enhancers in mesoderm to regulate hematopoietic and cardiac fate divergence. EMBO J. 2015 Mar 12; 34(6):759-77.
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Generation of genomic deletions in mammalian cell lines via CRISPR/Cas9. J Vis Exp. 2015 Jan 03; (95):e52118.
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Complementary genomic approaches highlight the PI3K/mTOR pathway as a common vulnerability in osteosarcoma. Proc Natl Acad Sci U S A. 2014 Dec 23; 111(51):E5564-73.
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Characterizing heterogeneity in leukemic cells using single-cell gene expression analysis. Genome Biol. 2014 Dec 03; 15(12):525.
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Mouse regulatory DNA landscapes reveal global principles of cis-regulatory evolution. Science. 2014 Nov 21; 346(6212):1007-12.
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A comparative encyclopedia of DNA elements in the mouse genome. Nature. 2014 Nov 20; 515(7527):355-64.
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Inflammatory signaling regulates embryonic hematopoietic stem and progenitor cell production. Genes Dev. 2014 Dec 01; 28(23):2597-612.
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Myeloproliferative neoplasms can be initiated from a single hematopoietic stem cell expressing JAK2-V617F. J Exp Med. 2014 Oct 20; 211(11):2213-30.
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TMEM14C is required for erythroid mitochondrial heme metabolism. J Clin Invest. 2014 Oct; 124(10):4294-304.
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Characterization of genomic deletion efficiency mediated by clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 nuclease system in mammalian cells. J Biol Chem. 2014 08 01; 289(31):21312-24.
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Reprogramming committed murine blood cells to induced hematopoietic stem cells with defined factors. Cell. 2014 Apr 24; 157(3):549-64.
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Distinct, strict requirements for Gfi-1b in adult bone marrow red cell and platelet generation. J Exp Med. 2014 May 05; 211(5):909-27.
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Corepressor Rcor1 is essential for murine erythropoiesis. Blood. 2014 May 15; 123(20):3175-84.
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Analysis of chromatin-state plasticity identifies cell-type-specific regulators of H3K27me3 patterns. Proc Natl Acad Sci U S A. 2014 Jan 21; 111(3):E344-53.
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Calpain 2 activation of P-TEFb drives megakaryocyte morphogenesis and is disrupted by leukemogenic GATA1 mutation. Dev Cell. 2013 Dec 23; 27(6):607-20.
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Distinct and combinatorial functions of Jmjd2b/Kdm4b and Jmjd2c/Kdm4c in mouse embryonic stem cell identity. Mol Cell. 2014 01 09; 53(1):32-48.
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GATA1s induces hyperproliferation of eosinophil precursors in Down syndrome transient leukemia. Leukemia. 2014 Jun; 28(6):1259-70.
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Polycomb repressive complex 2 regulates normal hematopoietic stem cell function in a developmental-stage-specific manner. Cell Stem Cell. 2014 Jan 02; 14(1):68-80.
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An erythroid enhancer of BCL11A subject to genetic variation determines fetal hemoglobin level. Science. 2013 Oct 11; 342(6155):253-7.
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Histone deacetylase inhibitors induce apoptosis in myeloid leukemia by suppressing autophagy. Leukemia. 2014 Mar; 28(3):577-88.
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Mapping cellular hierarchy by single-cell analysis of the cell surface repertoire. Cell Stem Cell. 2013 Oct 03; 13(4):492-505.
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Targeted disruption of the EZH2-EED complex inhibits EZH2-dependent cancer. Nat Chem Biol. 2013 Oct; 9(10):643-50.
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Delineating the mixed lineage leukemia gene expression network in hematopoietic stem cells. Proc Natl Acad Sci U S A. 2013 Jul 16; 110(29):11670-1.
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Histone demethylase Lsd1 represses hematopoietic stem and progenitor cell signatures during blood cell maturation. Elife. 2013 Jun 18; 2:e00633.
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Corepressor-dependent silencing of fetal hemoglobin expression by BCL11A. Proc Natl Acad Sci U S A. 2013 Apr 16; 110(16):6518-23.
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ETV1 directs androgen metabolism and confers aggressive prostate cancer in targeted mice and patients. Genes Dev. 2013 Mar 15; 27(6):683-98.
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Genome-wide association studies of hematologic phenotypes: a window into human hematopoiesis. Curr Opin Genet Dev. 2013 Jun; 23(3):339-44.
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Sustained PU.1 levels balance cell-cycle regulators to prevent exhaustion of adult hematopoietic stem cells. Mol Cell. 2013 Mar 07; 49(5):934-46.
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The switch from fetal to adult hemoglobin. Cold Spring Harb Perspect Med. 2013 Jan 01; 3(1):a011643.
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TiF1-gamma plays an essential role in murine hematopoiesis and regulates transcriptional elongation of erythroid genes. Dev Biol. 2013 Jan 15; 373(2):422-30.
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Altered hematopoiesis in trisomy 21 as revealed through in vitro differentiation of isogenic human pluripotent cells. Proc Natl Acad Sci U S A. 2012 Oct 23; 109(43):17567-72.
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Combinatorial assembly of developmental stage-specific enhancers controls gene expression programs during human erythropoiesis. Dev Cell. 2012 Oct 16; 23(4):796-811.
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Cyclin D3 coordinates the cell cycle during differentiation to regulate erythrocyte size and number. Genes Dev. 2012 Sep 15; 26(18):2075-87.
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Reawakening fetal hemoglobin: prospects for new therapies for the ß-globin disorders. Blood. 2012 Oct 11; 120(15):2945-53.
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Scl represses cardiomyogenesis in prospective hemogenic endothelium and endocardium. Cell. 2012 Aug 03; 150(3):590-605.
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The CACCC-binding protein KLF3/BKLF represses a subset of KLF1/EKLF target genes and is required for proper erythroid maturation in vivo. Mol Cell Biol. 2012 Aug; 32(16):3281-92.
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Exome sequencing identifies GATA1 mutations resulting in Diamond-Blackfan anemia. J Clin Invest. 2012 Jul; 122(7):2439-43.
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MAnorm: a robust model for quantitative comparison of ChIP-Seq data sets. Genome Biol. 2012 Mar 16; 13(3):R16.
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Polycomb repressive complex 2 is required for MLL-AF9 leukemia. Proc Natl Acad Sci U S A. 2012 Mar 27; 109(13):5028-33.
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MicroRNA-21 integrates pathogenic signaling to control pulmonary hypertension: results of a network bioinformatics approach. Circulation. 2012 Mar 27; 125(12):1520-32.
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A human stem cell model of early Alzheimer's disease pathology in Down syndrome. Sci Transl Med. 2012 Mar 07; 4(124):124ra29.
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Haploinsufficiency of Dnmt1 impairs leukemia stem cell function through derepression of bivalent chromatin domains. Genes Dev. 2012 Feb 15; 26(4):344-9.
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MicroRNA-21 promotes fibrosis of the kidney by silencing metabolic pathways. Sci Transl Med. 2012 Feb 15; 4(121):121ra18.
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Generation of a genomic reporter assay system for analysis of ?- and ß-globin gene regulation. FASEB J. 2012 Apr; 26(4):1736-44.
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PRC2 directly methylates GATA4 and represses its transcriptional activity. Genes Dev. 2012 Jan 01; 26(1):37-42.
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Dnmt3a silences hematopoietic stem cell self-renewal. Nat Genet. 2011 Dec 27; 44(1):13-4.
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Polycomb repressive complex 2 regulates normal development of the mouse heart. Circ Res. 2012 Feb 03; 110(3):406-15.
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Embryonic stem cell-specific signatures in cancer: insights into genomic regulatory networks and implications for medicine. Genome Med. 2011 Nov 29; 3(11):75.
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Zfp281 functions as a transcriptional repressor for pluripotency of mouse embryonic stem cells. Stem Cells. 2011 Nov; 29(11):1705-16.
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Correction of sickle cell disease in adult mice by interference with fetal hemoglobin silencing. Science. 2011 Nov 18; 334(6058):993-6.
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Sox2 maintains self renewal of tumor-initiating cells in osteosarcomas. Oncogene. 2012 May 03; 31(18):2270-82.
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A functional element necessary for fetal hemoglobin silencing. N Engl J Med. 2011 Sep 01; 365(9):807-14.
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MicroRNA-21 limits in vivo immune response-mediated activation of the IL-12/IFN-gamma pathway, Th1 polarization, and the severity of delayed-type hypersensitivity. J Immunol. 2011 Sep 15; 187(6):3362-73.
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Loss of the retinoblastoma binding protein 2 (RBP2) histone demethylase suppresses tumorigenesis in mice lacking Rb1 or Men1. Proc Natl Acad Sci U S A. 2011 Aug 16; 108(33):13379-86.
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Chromatin connections to pluripotency and cellular reprogramming. Cell. 2011 Jun 10; 145(6):835-50.
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Genome Medicine: stem cells, genomics and translational research. Genome Med. 2011 Jun 07; 3(6):34.
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The erythroid/myeloid lineage fate paradigm takes a new player. EMBO J. 2011 Mar 16; 30(6):983-5.
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Early pre-B cells from normal and X-linked agammaglobulinaemia produce C mu without an attached VH region. Nature. 1983 Jul 28-Aug 3; 304(5924):355-8.
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Molecular heterogeneity of inherited antithrombin III deficiency. N Engl J Med. 1983 Jun 30; 308(26):1549-52.
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The molecular basis for the clinical diversity of beta thalassaemia in Cypriots. Lancet. 1983 Jun 04; 1(8336):1235-7.
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Direct detection of the common Mediterranean beta-thalassemia gene with synthetic DNA probes. An alternative approach for prenatal diagnosis. J Clin Invest. 1983 Mar; 71(3):775-9.
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Controlling the fetal globin switch in man. Nature. 1983 Jan 13; 301(5896):108-9.
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Isolation and DNA sequence of a full-length cDNA clone for human X chromosome-encoded phosphoglycerate kinase. Proc Natl Acad Sci U S A. 1983 Jan; 80(2):472-6.
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Abnormal RNA processing due to the exon mutation of beta E-globin gene. Nature. 1982 Dec 23; 300(5894):768-9.
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