Stuart H Orkin

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. Perry J, Kiezun A, Tonzi P, Van Allen E, Carter S, Baca S, et al. Complementary genomic approaches highlight the PI3K/mTOR pathway as a common vulnerability in osteosarcoma. Proc Natl Acad Sci U S A. 2014;111:E5564-73 pubmed publisher
    ..Osteosarcoma cell lines are responsive to pharmacologic and genetic inhibition of the PI3K/mTOR pathway both in vitro and in vivo. ..
  2. Lessard S, Francioli L, Alföldi J, Tardif J, Ellinor P, MacArthur D, et al. Human genetic variation alters CRISPR-Cas9 on- and off-targeting specificity at therapeutically implicated loci. Proc Natl Acad Sci U S A. 2017;114:E11257-E11266 pubmed publisher
  3. Orkin S, Zon L. Hematopoiesis: an evolving paradigm for stem cell biology. Cell. 2008;132:631-44 pubmed publisher
  4. Barros Silva J, Linn D, Steiner I, Guo G, Ali A, Pakula H, et al. Single-Cell Analysis Identifies LY6D as a Marker Linking Castration-Resistant Prostate Luminal Cells to Prostate Progenitors and Cancer. Cell Rep. 2018;25:3504-3518.e6 pubmed publisher
    ..Our studies thus identify a subpopulation of luminal progenitors characterized by LY6D expression and intrinsic castration resistance. LY6D may serve as a prognostic maker for advanced prostate cancer. ..
  5. Bauer D, Canver M, Orkin S. Generation of genomic deletions in mammalian cell lines via CRISPR/Cas9. J Vis Exp. 2015;:e52118 pubmed publisher
    ..This approach can be used for efficient loss-of-function studies of genes and genetic elements in mammalian cell lines. ..
  6. Das P, Hendrix D, Apostolou E, Buchner A, Canver M, Beyaz S, et al. 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;12:1456-70 pubmed publisher
    ..Our observations are consistent with a mechanism through which PRC2 counteracts the action of Dnmt3 methyltransferases at an imprinted locus required for full pluripotency. ..
  7. Bauer D, Orkin S. Hemoglobin switching's surprise: the versatile transcription factor BCL11A is a master repressor of fetal hemoglobin. Curr Opin Genet Dev. 2015;33:62-70 pubmed publisher
    ..These discoveries have suggested novel rational approaches for the β-hemoglobin disorders including therapeutic genome editing. ..
  8. SMITH E, Orkin S. Hemoglobin genetics: recent contributions of GWAS and gene editing. Hum Mol Genet. 2016;25:R99-R105 pubmed
    ..In addition, we discuss other factors that may be involved in ?-globin gene silencing and their potential manipulation for therapeutic benefit in treating the ?-hemoglobinopathies. ..
  9. Maclean G, McEldoon J, Huang J, Allred J, Canver M, Orkin S. Downregulation of Endothelin Receptor B Contributes to Defective B Cell Lymphopoiesis in Trisomy 21 Pluripotent Stem Cells. Sci Rep. 2018;8:8001 pubmed publisher
    ..Furthermore, a novel role for endothelin signaling in regulation of B cell development has been identified. ..

More Information

Publications19

  1. Liu N, Hargreaves V, Zhu Q, Kurland J, Hong J, Kim W, et al. Direct Promoter Repression by BCL11A Controls the Fetal to Adult Hemoglobin Switch. Cell. 2018;173:430-442.e17 pubmed publisher
    ..Our findings reveal that direct γ-globin gene promoter repression by BCL11A underlies hemoglobin switching. ..
  2. Guo G, Pinello L, Han X, Lai S, Shen L, Lin T, et al. Serum-Based Culture Conditions Provoke Gene Expression Variability in Mouse Embryonic Stem Cells as Revealed by Single-Cell Analysis. Cell Rep. 2016;14:956-965 pubmed publisher
    ..Finally, we provide evidence that a large proportion of intracellular network variability is due to the extracellular culture environment. Serum-free culture reduces cellular heterogeneity and transcriptome variation in ESCs. ..
  3. Canver M, Bauer D, Orkin S. Functional interrogation of non-coding DNA through CRISPR genome editing. Methods. 2017;121-122:118-129 pubmed publisher
    ..Here we review CRISPR-based loss- and gain-of-function techniques for the interrogation of non-coding DNA. ..
  4. Canver M, Bauer D, Dass A, Yien Y, Chung J, Masuda T, et al. Characterization of genomic deletion efficiency mediated by clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 nuclease system in mammalian cells. J Biol Chem. 2014;289:21312-24 pubmed publisher
    ..We demonstrate an inverse relationship between deletion frequency and deletion size. This work suggests that CRISPR/Cas9 is a robust system to produce a spectrum of genomic deletions to allow investigation of genes and genetic elements. ..
  5. Orkin S, Hochedlinger K. Chromatin connections to pluripotency and cellular reprogramming. Cell. 2011;145:835-50 pubmed publisher
    ..Manipulation of cell state through the process of transdifferentiation suggests that environmental cues may direct transcriptional programs as cells enter a transiently "plastic" state during reprogramming. ..
  6. Balbach S, Orkin S. An Achilles' Heel for MLL-Rearranged Leukemias: Writers and Readers of H3 Lysine 36 Dimethylation. Cancer Discov. 2016;6:700-2 pubmed publisher
    ..Cancer Discov; 6(7); 700-2. ©2016 AACR.See related article by Zhu and colleagues, p. 770. ..
  7. Xie H, Peng C, Huang J, Li B, Kim W, SMITH E, et al. Chronic Myelogenous Leukemia- Initiating Cells Require Polycomb Group Protein EZH2. Cancer Discov. 2016;6:1237-1247 pubmed
    ..Cancer Discov; 6(11); 1237-47. ©2016 AACR.See related article by Scott et al., p. 1248This article is highlighted in the In This Issue feature, p. 1197. ..
  8. Luc S, Huang J, McEldoon J, Somuncular E, Li D, Rhodes C, et al. Bcl11a Deficiency Leads to Hematopoietic Stem Cell Defects with an Aging-like Phenotype. Cell Rep. 2016;16:3181-3194 pubmed publisher
    ..Our studies define a mechanism for BCL11A in regulation of HSC function and have important implications for the design of therapeutic approaches to targeting BCL11A. ..
  9. Hsu J, Hubbell Engler B, Adelmant G, Huang J, Joyce C, Vazquez F, et al. PRMT1-Mediated Translation Regulation Is a Crucial Vulnerability of Cancer. Cancer Res. 2017;77:4613-4625 pubmed publisher
    ..i>Cancer Res; 77(17); 4613-25. ©2017 AACR. ..
  10. Xie H, Xu J, Hsu J, Nguyen M, Fujiwara Y, Peng C, et al. Polycomb repressive complex 2 regulates normal hematopoietic stem cell function in a developmental-stage-specific manner. Cell Stem Cell. 2014;14:68-80 pubmed publisher
    ..Taken together, our findings define developmental-stage-specific requirements for canonical PRC2 complexes in normal HSC function. ..