Browsing by Author "Ebert, Benjamin"

Now showing items 1-20 of 26

    • The CDK Inhibitor CR8 Acts as a Molecular Glue Degrader That Depletes Cyclin K 

      Słabicki, Mikołaj; Kozicka, Zuzanna; Petzold, Georg; Li, Yen-Der; Manojkumar, Manisha; Bunker, Richard D.; Donovan, Katherine A.; Sievers, Quinlan; Koeppel, Jonas; Suchyta, Dakota; Sperling, Adam S.; Fink, Emma C.; Gasser, Jessica; Wang, Li R.; Corsello, Steven M.; Sellar, Rob S.; Jan, Max; Gillingham, Dennis; Scholl, Claudia; Fröhling, Stefan; Golub, Todd; Fischer, Eric S.; Thomä, Nicolas H.; Ebert, Benjamin (Springer Science and Business Media LLC, 2020-06-03)
      Molecular glue compounds induce protein-protein interactions that, in the context of a ubiquitin ligase, lead to protein degradation. Unlike traditional enzyme inhibitors, such molecular glue degraders act sub-stoichiometrically ...

    • 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 ...

    • Defining the Human C2H2 Zinc Finger Degrome Targeted by Thalidomide Analogs Through CRBN 

      Sievers, Quinlan L.; Petzold, Georg; Bunker, Richard D.; Renneville, Aline; Slabicki, Mikolaj; Liddicoat, Brian J.; Abdulrahman, Wassim; Mikkelsen, Tarjei; Ebert, Benjamin; Thomä, Nicolas H. (American Association for the Advancement of Science (AAAS), 2018-11-02)
      The small molecules thalidomide, lenalidomide, and pomalidomide induce the ubiquitination and proteasomal degradation of the transcription factors Ikaros (IKZF1) and Aiolos (IKZF3) by recruiting a Cys2-His2 (C2H2) zinc ...

    • 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 ...

    • Hematopoietic mosaic chromosomal alterations increase the risk for diverse types of infection 

      Zekavat, Seyedeh M.; Lin, Shu-Hong; Bick, Alexander G.; Liu, Aoxing; Paruchuri, Kaavya; Wang, Chen; Uddin, Md Mesbah; Ye, Yixuan; Yu, Zhaolong; Liu, Xiaoxi; Kamatani, Yoichiro; Bhattacharya, Romit; Pirruccello, James; Pampana, Akhil; Loh, Po-Ru; Kohli, Puja; McCarroll, Steven; Kiryluk, Krzysztof; Neale, Benjamin; Ionita-Laza, Iuliana; Engels, Eric; Brown, Derek W.; Smoller, Jordan; Green, Robert; Karlson, Elizabeth; Lebo, Matthew; Ellinor, Patrick; Weiss, Scott; Daly, Mark; Terao, Chikashi; Zhao, Hongyu; Ebert, Benjamin; Reilly, Muredach; Ganna, Andrea; Machiela, Mitchell; Genovese, Giulio; Natarajan, Pradeep (Springer Science and Business Media LLC, 2021-06)
      The burden of mosaic chromosomal alterations in blood-derived DNA, a type of clonal hematopoiesis, is associated with an increased risk for diverse types of infections, including sepsis and pneumonia. Age is the dominant ...

    • 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, ...

    • Inherited Causes of Clonal Haematopoiesis in 97,691 Whole Genomes 

      Bick, Alexander; Weinstock, Joshua S.; Nandakumar, Satish K.; Fulco, Charles P.; Bao, Erik; Zekavat, Seyedeh M.; Szeto, Mindy D.; Liao, Xiaotian; Leventhal, Matthew J.; Nasser, Joseph; Chang, Kyle; Laurie, Cecelia; Burugula, Bala Bharathi; Gibson, Christopher J.; Niroula, Abhishek; Lin, Amy; Taub, Margaret A.; Aguet, Francois; Ardlie, Kristin; Mitchell, Braxton D.; Barnes, Kathleen C.; Moscati, Arden; Fornage, Myriam; Redline, Susan; Psaty, Bruce M.; Silverman, Edwin; Weiss, Scott; Palmer, Nicholette D.; Vasan, Ramachandran S.; Burchard, Esteban G.; Kardia, Sharon L. R.; He, Jiang; Kaplan, Robert C.; Smith, Nicholas L.; Arnett, Donna K.; Schwartz, David A.; Correa, Adolfo; de Andrade, Mariza; Guo, Xiuqing; Konkle, Barbara A.; Custer, Brian; Peralta, Juan M.; Gui, Hongsheng; Meyers, Deborah A.; McGarvey, Stephen T.; Chen, Ida Yii-Der; Shoemaker, M. Benjamin; Peyser, Patricia A.; Broome, Jai G.; Gogarten, Stephanie M.; Wang, Fei Fei; Wong, Quenna; Montasser, May E.; Daya, Michelle; Kenny, Eimear E.; North, Kari E.; Launer, Lenore J.; Cade, Brian; Bis, Joshua C.; Cho, Michael; Lasky-Su, Jessica; Bowden, Donald W.; Cupples, L. Adrienne; Mak, Angel C. Y.; Becker, Lewis C.; Smith, Jennifer A.; Kelly, Tanika N.; Aslibekyan, Stella; Heckbert, Susan R.; Tiwari, Hemant K.; Yang, Ivana V.; Heit, John A.; Lubitz, Steven; Johnsen, Jill M.; Curran, Joanne E.; Wenzel, Sally E.; Weeks, Daniel E.; Rao, Dabeeru C.; Darbar, Dawood; Moon, Jee-Young; Tracy, Russell P.; Buth, Erin J.; Rafaels, Nicholas; Loos, Ruth J. F.; Durda, Peter; Liu, Yongmei; Hou, Lifang; Lee, Jiwon; Kachroo, Priyadarshini; Freedman, Barry I.; Levy, Daniel; Bielak, Lawrence F.; Hixson, James E.; Floyd, James S.; Whitsel, Eric A.; Ellinor, Patrick; Irvin, Marguerite R.; Fingerlin, Tasha E.; Raffield, Laura M.; Armasu, Sebastian M.; Wheeler, Marsha M.; Sabino, Ester C.; Blangero, John; Williams, L. Keoki; Levy, Bruce; Sheu, Wayne Huey-Herng; Roden, Dan M.; Boerwinkle, Eric; Manson, JoAnn; Mathias, Rasika A.; Desai, Pinkal; Taylor, Kent D.; Johnson, Andrew D.; Auer, Paul L.; Kooperberg, Charles; Laurie, Cathy C.; Blackwell, Thomas W.; Smith, Albert V.; Zhao, Hongyu; Lange, Ethan; Lange, Leslie; Rich, Stephen S.; Rotter, Jerome I.; Wilson, James G.; Scheet, Paul; Kitzman, Jacob O.; Lander, Eric; Engreitz, Jesse; Ebert, Benjamin; Reiner, Alexander P.; Jaiswal, Siddhartha; Abecasis, Gonçalo; Sankaran, Vijay; Kathiresan, Sekar; Natarajan, Pradeep (Springer Science and Business Media LLC, 2020-10-14)
      Age is the dominant risk factor for most chronic human diseases; yet the mechanisms by which aging confers this risk are largely unknown. Recently, the age-related acquisition of somatic mutations in regenerating hematopoietic ...

    • 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. ...