Stuart H Orkin
Affiliation: Harvard University
- 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....
- 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. ..
- 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. ..
- 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 ?-globin gene promoter repression by BCL11A underlies hemoglobin switching. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..