Now showing items 1-20 of 22

    • Chemical genetic strategy identifies histone deacetylase 1 (HDAC1) and HDAC2 as therapeutic targets in sickle cell disease 

      Bradner, James Elliott; Mak, Raymond Heungwing; Tanguturi, Shyam Kumar; Mazitschek, Ralph; Haggarty, Stephen John; Ross, Kenneth N; Chang, Cindy Y.; Bosco, Jocelyn; West, Nathan; Morse, Elizabeth; Lin, Katherine; Shen, John Paul; Kwiatkowski, Nicholas Paul; Gheldof, Nele; Dekker, Job; DeAngelo, Daniel J.; Carr, Steven A.; Schreiber, Stuart L.; Golub, Todd Robert; Ebert, Benjamin L. (Proceedings of the National Academy of Sciences, 2010)
      The 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 ...
    • Csnk1a1 inhibition has p53-dependent therapeutic efficacy in acute myeloid leukemia 

      Järås, Marcus; Miller, Peter G.; Chu, Lisa P.; Puram, Rishi V.; Fink, Emma C.; Schneider, Rebekka K.; Al-Shahrour, Fatima; Peña, Pablo; Breyfogle, L. Jordan; Hartwell, Kimberly A.; McConkey, Marie E.; Cowley, Glenn S.; Root, David E.; Kharas, Michael G.; Mullally, Ann; Ebert, Benjamin L. (The Rockefeller University Press, 2014)
      Despite extensive insights into the underlying genetics and biology of acute myeloid leukemia (AML), overall survival remains poor and new therapies are needed. We found that casein kinase 1 α (Csnk1a1), a serine-threonine ...
    • Defining and Targeting Transcriptional Pathways in Leukemia Stem Cells 

      Puram, Rishi Venkata (2014-10-21)
      Acute myeloid leukemia (AML) is a clonal neoplastic disorder organized as a cellular hierarchy, with the self-renewing leukemia stem cell (LSC) at the apex. Recurrent mutations in transcription factors (TF) and epigenetic ...
    • Densely Interconnected Transcriptional Circuits Control Cell States in Human Hematopoiesis 

      Novershtern, Noa; Subramanian, Aravind; Lawton, Lee N.; Mak, Raymond Heungwing; Haining, William Nicholas; McConkey, Marie E.; Habib, Naomi; Yosef, Nir; Chang, Cindy Hsin-Yu; Shay, Tal; Frampton, Garrett M.; Drake, Adam C.B.; Leskov, Ilya; Nilsson, Bjorn; Preffer, Frederic Ira; Dombkowski, David; Evans, John W.; Liefeld, Ted; Smutko, John S.; Chen, Jianzhu; Friedman, Nir; Young, Richard A.; Golub, Todd Robert; Regev, Aviv; Ebert, Benjamin L. (Elsevier BV, 2011)
      While many individual transcription factors are known to regulate hematopoietic differentiation, major aspects of the global architecture of hematopoiesis remain unknown. Here, we profiled gene expression in 38 distinct ...
    • Developmental Maturation within the Hematopoietic System 

      Arora, Natasha (2014-06-06)
      Stem cell biologists creating cells and tissues for therapies, disease modeling, and drug screening have observed that differentiating pluripotent stem cells (PSCs) tend to produce cells at an embryonic stage of development ...
    • Drosophila glucome screening identifies Ck1alpha as a regulator of mammalian glucose metabolism 

      Ugrankar, Rupali; Berglund, Eric; Akdemir, Fatih; Tran, Christopher; Kim, Min Soo; Noh, Jungsik; Schneider, Rebekka; Ebert, Benjamin; Graff, Jonathan M. (Nature Pub. Group, 2015)
      Circulating carbohydrates are an essential energy source, perturbations in which are pathognomonic of various diseases, diabetes being the most prevalent. Yet many of the genes underlying diabetes and its characteristic ...
    • An engineered multicomponent bone marrow niche for the recapitulation of hematopoiesis at ectopic transplantation sites 

      Ventura Ferreira, Mónica S.; Bergmann, Christian; Bodensiek, Isabelle; Peukert, Kristina; Abert, Jessica; Kramann, Rafael; Kachel, Paul; Rath, Björn; Rütten, Stephan; Knuchel, Ruth; Ebert, Benjamin L.; Fischer, Horst; Brümmendorf, Tim H.; Schneider, Rebekka K. (BioMed Central, 2016)
      Background: Bone marrow (BM) niches are often inaccessible for controlled experimentation due to their difficult accessibility, biological complexity, and three-dimensional (3D) geometry. Methods: Here, we report the ...
    • Epigenetics of TET2 Loss in Myelodysplastic Syndromes 

      Lord, Allegra (2015-05-18)
      Myelodysplastic syndromes (MDS) are a class of myeloid malignancy characterized by peripheral blood cytopenias and impaired hematopoietic differentiation. Our understanding of the molecular basis of MDS has improved ...
    • An Erythroid Differentiation Signature Predicts Response to Lenalidomide in Myelodysplastic Syndrome 

      Galili, Naomi; Tamayo, Pablo; Bosco, Jocelyn; Ladd-Acosta, Christine; Raza, Azra; Ebert, Benjamin L.; Mak, Raymond Heungwing; Pretz, Jennifer Lee; Tanguturi, Shyam Kumar; Stone, Richard Maury; Golub, Todd R. (Public Library of Science, 2008)
      Background: Lenalidomide is an effective new agent for the treatment of patients with myelodysplastic syndrome (MDS), an acquired hematopoietic disorder characterized by ineffective blood cell production and a predisposition ...
    • Functional characterization of genetic alterations in cancer 

      Kim, Eejung (2016-05-18)
      The comprehensive identification of genetic alterations is critical to understanding the pathophysiology of cancer. Recent advances in sequencing technology have enabled the detailed description of cancer genomes. However, ...
    • Generation of mouse models of myeloid malignancy with combinatorial genetic lesions using CRISPR-Cas9 genome editing 

      Heckl, Dirk; Kowalczyk, Monika S.; Yudovich, David; Belizaire, Roger; Puram, Rishi V.; McConkey, Marie E.; Thielke, Anne; Aster, Jon C.; Regev, Aviv; Ebert, Benjamin L. (2014)
      Genome sequencing studies have shown that human malignancies often bear mutations in four or more driver genes1, but it is difficult to recapitulate this degree of genetic complexity in mouse models using conventional ...
    • Heterodimeric JAK-STAT Activation as a Mechanism of Persistence to JAK2 Inhibitor Therapy 

      Koppikar, Priya; Bhagwat, Neha; Kilpivaara, Outi; Manshouri, Taghi; Adli, Mazhar; Hricik, Todd; Liu, Fan; Saunders, Lindsay M.; Mullally, Ann; Abdel-Wahab, Omar; Leung, Laura; Weinstein, Abby; Marubayashi, Sachie; Goel, Aviva; Gönen, Mithat; Estrov, Zeev; Ebert, Benjamin L.; Chiosis, Gabriela; Nimer, Stephen D.; Bernstein, Bradley E.; Verstovsek, Srdan; Levine, Ross L. (2012)
      The identification of somatic activating mutations in JAK21–4 and in the thrombopoietin receptor (MPL)5 in the majority of myeloproliferative neoplasm (MPN) patients led to the clinical development of JAK2 kinase inhibitors6,7. ...
    • Identification of RPS14 as a 5q- syndrome gene by RNA interference screen 

      Ebert, Benjamin L.; Pretz, Jennifer; Bosco, Jocelyn; Chang, Cindy Y.; Tamayo, Pablo; Galili, Naomi; Raza, Azra; Root, David E.; Attar, Eyal; Ellis, Steven R.; Golub, Todd R. (2013)
      Somatic chromosomal deletions in cancer are thought to indicate the location of tumor suppressor genes, whereby complete loss of gene function occurs through biallelic deletion, point mutation, or epigenetic silencing, ...
    • Interrogation of the RP-MDM2-P53 Axis in Human Ribosomopathies 

      Raiser, David Michael (2015-05-15)
      Ribosomopathies such as Diamond-Blackfan anemia (DBA) and 5q- syndrome are human diseases characterized by heterozygous loss or mutation of ribosome-associated genes. Hallmarks of these diseases include a macrocytic anemia ...
    • Loss of Function of TET2 Cooperates with Constitutively Active KIT in Murine and Human Models of Mastocytosis 

      De Vita, Serena; Schneider, Rebekka K.; Garcia, Michael; Wood, Jenna; Gavillet, Mathilde; Ebert, Benjamin L.; Gerbaulet, Alexander; Roers, Axel; Levine, Ross L.; Mullally, Ann; Williams, David A. (Public Library of Science, 2014)
      Systemic Mastocytosis (SM) is a clonal disease characterized by abnormal accumulation of mast cells in multiple organs. Clinical presentations of the disease vary widely from indolent to aggressive forms, and to the ...
    • Macrophages support pathological erythropoiesis in Polycythemia Vera and Beta-Thalassemia 

      Ramos, Pedro; Casu, Carla; Gardenghi, Sara; Breda, Laura; Crielaard, Bart J.; Guy, Ella; Marongiu, Maria Franca; Gupta, Ritama; Levine, Ross L.; Abdel-Wahab, Omar; Ebert, Benjamin L.; Van Rooijen, Nico; Ghaffari, Saghi; Grady, Robert W.; Giardina, Patricia J.; Rivella, Stefano (2013)
      Regulation of erythropoiesis is achieved by integration of distinct signals. Among these, macrophages are emerging as erythropoietin-complementary regulators of erythroid development, particularly under stress conditions. ...
    • MicroRNA-Mediated Control of Cell Fate in Megakaryocyte-Erythrocyte Progenitors 

      Lu, Jun; Guo, Shangqin; Ebert, Benjamin L.; Zhang, Hao; Peng, Xiao; Bosco, Jocelyn; Pretz, Jennifer Lee; Schlanger, Rita; Wang, Judy Y.; Mak, Raymond Heungwing; Dombkowski, David M.; Preffer, Frederic Ira; Scadden, David Thomas; Golub, Todd Robert (Elsevier BV, 2008)
      Lineage specification is a critical issue in developmental and regenerative biology. We hypothesized that microRNAs (miRNAs) are important participants in that process and used the poorly-understood regulation of ...
    • Mitochondrial Atpif1 regulates heme synthesis in developing erythroblasts 

      Shah, Dhvanit I; Takahashi-Makise, Naoko; Cooney, Jeffrey D.; Li, Liangtao; Schultz, Iman J.; Pierce, Eric L.; Narla, Anupama; Seguin, Alexandra; Hattangadi, Shilpa M.; Medlock, Amy E.; Langer, Nathaniel B.; Dailey, Tamara A.; Hurst, Slater N.; Faccenda, Danilo; Wiwczar, Jessica M.; Heggers, Spencer K.; Vogin, Guillaume; Chen, Wen; Chen, Caiyong; Campagna, Dean R.; Brugnara, Carlo; Zhou, Yi; Ebert, Benjamin L.; Danial, Nika; Fleming, Mark Daniel; Ward, Diane M.; Campanella, Michelangelo; Dailey, Harry A.; Kaplan, Jerry; Paw, Barry Htin (2012)
      SUMMARY Defects in the availability of heme substrates or the catalytic activity of the terminal enzyme in heme biosynthesis, ferrochelatase (Fech), impair heme synthesis, and thus cause human congenital anemias1,2. The ...
    • Musashi-2 controls cell fate, lineage bias, and TGF-β signaling in HSCs 

      Park, Sun-Mi; Deering, Raquel P.; Lu, Yuheng; Tivnan, Patrick; Lianoglou, Steve; Al-Shahrour, Fatima; Ebert, Benjamin L.; Hacohen, Nir; Leslie, Christina; Daley, George Q.; Lengner, Christopher J.; Kharas, Michael G. (The Rockefeller University Press, 2014)
      Hematopoietic stem cells (HSCs) are maintained through the regulation of symmetric and asymmetric cell division. We report that conditional ablation of the RNA-binding protein Msi2 results in a failure of HSC maintenance ...
    • Mutations in epigenetic regulators including SETD2 are gained during relapse in pediatric acute lymphoblastic leukemia 

      Mar, Brenton G; Bullinger, Lars B; McLean, Kathleen M; Grauman, Peter V; Harris, Marian H; Stevenson, Kristen; Neuberg, Donna S; Sinha, Amit U; Sallan, Stephen E; Silverman, Lewis B; Kung, Andrew L; Nigro, Luca Lo; Ebert, Benjamin L; Armstrong, Scott A (2014)
      Relapsed pediatric acute lymphoblastic leukemia (ALL) has high rates of treatment failure. Epigenetic regulators have been proposed as modulators of chemoresistance, here we sequence genes encoding epigenetic regulators ...