Jon C Aster

Summary

Affiliation: Massachusetts General Hospital
Country: USA

Publications

  1. ncbi request reprint F3/contactin acts as a functional ligand for Notch during oligodendrocyte maturation
    Qi Dong Hu
    Department of Clinical Research, Singapore General Hospital, 169608, Singapore, Singapore
    Cell 115:163-75. 2003
  2. ncbi request reprint Notch signaling in leukemia
    Jon C Aster
    Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Annu Rev Pathol 3:587-613. 2008
  3. pmc A mutation in separase causes genome instability and increased susceptibility to epithelial cancer
    Jennifer L Shepard
    Children s Hospital, Boston, Massachusetts 02115, USA
    Genes Dev 21:55-9. 2007
  4. ncbi request reprint FAS death domain deletions and cellular FADD-like interleukin 1beta converting enzyme inhibitory protein (long) overexpression: alternative mechanisms for deregulating the extrinsic apoptotic pathway in diffuse large B-cell lymphoma subtypes
    Hidenobu Takahashi
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Clin Cancer Res 12:3265-71. 2006
  5. ncbi request reprint Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia
    Andrew P Weng
    Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Science 306:269-71. 2004
  6. ncbi request reprint NFkappaB activity, function, and target-gene signatures in primary mediastinal large B-cell lymphoma and diffuse large B-cell lymphoma subtypes
    Friedrich Feuerhake
    Department of Medical Oncology, Dana Farber Cancer Institute, 44 Binney St, Boston, MA 02115, USA
    Blood 106:1392-9. 2005
  7. pmc Notch ankyrin repeat domain variation influences leukemogenesis and Myc transactivation
    Jon C Aster
    Department of Pathology, Brigham and Women s Hospital, Boston, Massachusetts, United States of America
    PLoS ONE 6:e25645. 2011
  8. pmc Infection and persistence of rhesus monkey rhadinovirus in immortalized B-cell lines
    John P Bilello
    New England Primate Research Center, Harvard Medical School, One Pine Hill Drive, Southborough, MA 01772 9102, USA
    J Virol 80:3644-9. 2006
  9. pmc Cooperative assembly of higher-order Notch complexes functions as a switch to induce transcription
    Yunsun Nam
    Department of Pathology, Brigham and Women s Hospital, and Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 104:2103-8. 2007
  10. ncbi request reprint Structural requirements for assembly of the CSL.intracellular Notch1.Mastermind-like 1 transcriptional activation complex
    Yunsun Nam
    Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 278:21232-9. 2003

Detail Information

Publications89

  1. ncbi request reprint F3/contactin acts as a functional ligand for Notch during oligodendrocyte maturation
    Qi Dong Hu
    Department of Clinical Research, Singapore General Hospital, 169608, Singapore, Singapore
    Cell 115:163-75. 2003
    ..Expression of constitutively active Notch1 or Notch2 does not upregulate MAG. Thus, F3/contactin specifically initiates a Notch/Deltex1 signaling pathway that promotes oligodendrocyte maturation and myelination...
  2. ncbi request reprint Notch signaling in leukemia
    Jon C Aster
    Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Annu Rev Pathol 3:587-613. 2008
    ..This review discusses what these mutations have taught us about normal and pathophysiologic Notch1 signaling, and how these insights may lead to new targeted therapies for patients with this aggressive form of cancer...
  3. pmc A mutation in separase causes genome instability and increased susceptibility to epithelial cancer
    Jennifer L Shepard
    Children s Hospital, Boston, Massachusetts 02115, USA
    Genes Dev 21:55-9. 2007
    ..These data strongly support a conserved cross-species role for mitotic checkpoint genes in genetic stability and epithelial carcinogenesis...
  4. ncbi request reprint FAS death domain deletions and cellular FADD-like interleukin 1beta converting enzyme inhibitory protein (long) overexpression: alternative mechanisms for deregulating the extrinsic apoptotic pathway in diffuse large B-cell lymphoma subtypes
    Hidenobu Takahashi
    Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Clin Cancer Res 12:3265-71. 2006
    ....
  5. ncbi request reprint Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia
    Andrew P Weng
    Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Science 306:269-71. 2004
    ..These findings greatly expand the role of activated NOTCH1 in the molecular pathogenesis of human T-ALL and provide a strong rationale for targeted therapies that interfere with NOTCH signaling...
  6. ncbi request reprint NFkappaB activity, function, and target-gene signatures in primary mediastinal large B-cell lymphoma and diffuse large B-cell lymphoma subtypes
    Friedrich Feuerhake
    Department of Medical Oncology, Dana Farber Cancer Institute, 44 Binney St, Boston, MA 02115, USA
    Blood 106:1392-9. 2005
    ..In this large series of primary MLBCLs and DLBCLs, NFkappaB activation was not associated with amplification of the cREL locus, suggesting alternative pathogenetic mechanisms...
  7. pmc Notch ankyrin repeat domain variation influences leukemogenesis and Myc transactivation
    Jon C Aster
    Department of Pathology, Brigham and Women s Hospital, Boston, Massachusetts, United States of America
    PLoS ONE 6:e25645. 2011
    ....
  8. pmc Infection and persistence of rhesus monkey rhadinovirus in immortalized B-cell lines
    John P Bilello
    New England Primate Research Center, Harvard Medical School, One Pine Hill Drive, Southborough, MA 01772 9102, USA
    J Virol 80:3644-9. 2006
    ..These results establish a naturalistic cell culture system for the study of infection and persistence by RRV in rhesus monkey B cells...
  9. pmc Cooperative assembly of higher-order Notch complexes functions as a switch to induce transcription
    Yunsun Nam
    Department of Pathology, Brigham and Women s Hospital, and Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 104:2103-8. 2007
    ....
  10. ncbi request reprint Structural requirements for assembly of the CSL.intracellular Notch1.Mastermind-like 1 transcriptional activation complex
    Yunsun Nam
    Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 278:21232-9. 2003
    ..ICN.CSL.DNA complex suggests that a primary function of ICN is to render CSL competent for MAML loading. On the basis of our results, we present a working structural model for the organization of the MAML1.ICN.CSL.DNA complex...
  11. pmc Notch subunit heterodimerization and prevention of ligand-independent proteolytic activation depend, respectively, on a novel domain and the LNR repeats
    Cheryll Sanchez-Irizarry
    Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, 77 Ave Louis Pasteur, Boston, MA 02115, USA
    Mol Cell Biol 24:9265-73. 2004
    ..Together, these two contiguous regions of N(EC) impose crucial restraints that prevent premature Notch receptor activation...
  12. pmc Effects of S1 cleavage on the structure, surface export, and signaling activity of human Notch1 and Notch2
    Wendy R Gordon
    Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS ONE 4:e6613. 2009
    ....
  13. pmc Mutational and energetic studies of Notch 1 transcription complexes
    Cristina Del Bianco
    Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    J Mol Biol 376:131-40. 2008
    ....
  14. ncbi request reprint Structural basis for cooperativity in recruitment of MAML coactivators to Notch transcription complexes
    Yunsun Nam
    Biological and Biomedical Sciences Graduate Program in the Division of Medical Sciences, Harvard Medical School, Boston, MA 02115, USA
    Cell 124:973-83. 2006
    ..The composite binding surface likely restricts the recruitment of MAML proteins to promoters on which Notch:CSL complexes have been preassembled, ensuring tight transcriptional control of Notch target genes...
  15. pmc A prospective study of Epstein-Barr virus antibodies and risk of non-Hodgkin lymphoma
    Kimberly A Bertrand
    Department of Epidemiology, Harvard School of Public Health, 677 Huntington Ave, Boston, MA 02115, USA
    Blood 116:3547-53. 2010
    ..Overall, we found no evidence that EBV antibody profile predicts NHL risk in immunocompetent persons, with the possible exception of chronic lymphocytic leukemia/small lymphocytic lymphoma...
  16. pmc Leukemia-associated mutations within the NOTCH1 heterodimerization domain fall into at least two distinct mechanistic classes
    Michael J Malecki
    Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    Mol Cell Biol 26:4642-51. 2006
    ..Together, these studies show that leukemia-associated HD domain mutations render NOTCH1 sensitive to ligand-independent proteolytic activation through two distinct mechanisms...
  17. ncbi request reprint Experimental rhesus lymphocryptovirus infection in immunosuppressed macaques: an animal model for Epstein-Barr virus pathogenesis in the immunosuppressed host
    Pierre Rivailler
    Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA
    Blood 104:1482-9. 2004
    ..These studies demonstrate the potential for lymphomagenesis in an experimental model system for EBV infection and underscore the strength and depth of immune control in limiting LCV-induced lymphoproliferative disease...
  18. pmc NOTCH1-RBPJ complexes drive target gene expression through dynamic interactions with superenhancers
    Hongfang Wang
    Department of Pathology, Brigham and Women s Hospital, Boston, MA 02115
    Proc Natl Acad Sci U S A 111:705-10. 2014
    ....
  19. ncbi request reprint Notch-1 regulates pulmonary neuroendocrine cell differentiation in cell lines and in transgenic mice
    Lin Shan
    Department of Pathology, Children s Hospital and Harvard Medical School, Boston, Massachusetts, USA
    Am J Physiol Lung Cell Mol Physiol 292:L500-9. 2007
    ..Cumulatively, these observations provide further support for a role for Notch-1 signaling in regulating pulmonary NE cell differentiation...
  20. pmc EBNA-3B- and EBNA-3C-regulated cellular genes in Epstein-Barr virus-immortalized lymphoblastoid cell lines
    Adrienne Chen
    Channing Laboratory, 181 Longwood Avenue, Boston, MA 02115, USA
    J Virol 80:10139-50. 2006
    ....
  21. ncbi request reprint TRAF1 expression and c-Rel activation are useful adjuncts in distinguishing classical Hodgkin lymphoma from a subset of morphologically or immunophenotypically similar lymphomas
    Scott J Rodig
    Department of Pathology, Brigham and Women s Hospital, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Am J Surg Pathol 29:196-203. 2005
    ....
  22. pmc Structure of the Notch1-negative regulatory region: implications for normal activation and pathogenic signaling in T-ALL
    Wendy R Gordon
    Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston, MA, USA
    Blood 113:4381-90. 2009
    ..The Notch1 NRR structure should facilitate a search for antibodies or compounds that stabilize the autoinhibited conformation...
  23. ncbi request reprint The BAL-binding protein BBAP and related Deltex family members exhibit ubiquitin-protein isopeptide ligase activity
    Kunihiko Takeyama
    Department of Medical Oncology, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
    J Biol Chem 278:21930-7. 2003
    ..Consistent with this idea, BBAP and DTX1 associate via their unique N termini, resulting in enhanced self-ubiquitination...
  24. pmc Plasma organochlorine levels and risk of non-Hodgkin lymphoma in the Nurses' Health Study
    Francine Laden
    Channing Laboratory, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA
    Cancer Epidemiol Biomarkers Prev 19:1381-4. 2010
    ..These results do not support the hypothesis of a positive association between PCB exposure and development of NHL...
  25. pmc Genome-wide analysis reveals conserved and divergent features of Notch1/RBPJ binding in human and murine T-lymphoblastic leukemia cells
    Hongfang Wang
    Department of Pathology, Brigham and Women s Hospital, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 108:14908-13. 2011
    ..Thus, there is a conserved network of cis-regulatory factors that interacts with Notch1 to regulate gene expression in TLL cells, as well as unique classes of divergent RBPJ-only sites that also likely regulate transcription...
  26. ncbi request reprint Structural basis for autoinhibition of Notch
    Wendy R Gordon
    Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, 77 Ave Louis Pasteur, Boston, Massachusetts 02115, USA
    Nat Struct Mol Biol 14:295-300. 2007
    ..Leukemia-associated mutations in NOTCH1 probably release autoinhibition by destabilizing the conserved hydrophobic core of the NRR...
  27. pmc Intrinsic selectivity of Notch 1 for Delta-like 4 over Delta-like 1
    Marie Blanke Andrawes
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 288:25477-89. 2013
    ....
  28. ncbi request reprint Nuclear magnetic resonance structure of a prototype Lin12-Notch repeat module from human Notch1
    Didem Vardar
    Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115, USA
    Biochemistry 42:7061-7. 2003
    ..These studies represent an initial step toward understanding the structural interrelationships among the three contiguous LNR modules required for proper regulation of Notch signaling...
  29. ncbi request reprint Myc-induced T cell leukemia in transgenic zebrafish
    David M Langenau
    Department of Pediatric Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Science 299:887-90. 2003
    ..This transgenic model provides a platform for drug screens and for genetic screens aimed at identifying mutations that suppress or enhance c-myc- induced carcinogenesis...
  30. pmc Activating Notch1 mutations in mouse models of T-ALL
    Jennifer O'Neil
    Department of Pediatric Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Blood 107:781-5. 2006
    ..Thus, Notch1 mutations are often acquired as a part of the molecular pathogenesis of T-ALLs that develop in mice with known predisposing genetic alterations...
  31. pmc An epigenetic mechanism of resistance to targeted therapy in T cell acute lymphoblastic leukemia
    Birgit Knoechel
    1 Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA 2 Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA 3 Department of Pediatric Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USA 4 Division of Hematology Oncology, Boston Children s Hospital and Harvard Medical School, Boston, Massachusetts, USA 5
    Nat Genet 46:364-70. 2014
    ..Our findings establish a role for epigenetic heterogeneity in leukemia resistance that may be addressed by incorporating epigenetic modulators in combination therapy. ..
  32. ncbi request reprint The molecular signature of mediastinal large B-cell lymphoma differs from that of other diffuse large B-cell lymphomas and shares features with classical Hodgkin lymphoma
    Kerry J Savage
    Dana Farber Cancer Institute, 44 Binney St, Boston, MA 02115, USA
    Blood 102:3871-9. 2003
    ..In almost all cases, c-REL was localized to the nucleus, consistent with activation of the NF-kappa B pathway. These studies identify a molecular link between MLBCL and cHL and a shared survival pathway...
  33. pmc Differentiation of NUT midline carcinoma by epigenomic reprogramming
    Brian E Schwartz
    Department of Pathology, Division of Women s and Perinatal Pathology, Brigham and Women s Hospital, Boston, Massachusetts, USA
    Cancer Res 71:2686-96. 2011
    ..An objective response was obtained after five weeks of therapy, as determined by positron emission tomography. These findings provide preclinical support for trials of HDACi in patients with NMC...
  34. doi request reprint Novel SSBP2-JAK2 fusion gene resulting from a t(5;9)(q14.1;p24.1) in pre-B acute lymphocytic leukemia
    Jennifer L Poitras
    Department of Pathology, Brigham and Women s Hospital, Boston, MA 02115, USA
    Genes Chromosomes Cancer 47:884-9. 2008
    ..This finding adds to the expanding compendium of JAK2 aberrations found in various hematopoietic malignancies, as well as the potential need for a diagnostic FISH analysis in the appropriate clinical setting...
  35. pmc Evidence for increased exposure of the Notch1 metalloprotease cleavage site upon conversion to an activated conformation
    Kittichoat Tiyanont
    Department of Cancer Biology, Dana Farber Cancer Institute, Boston, MA 02115, USA
    Structure 19:546-54. 2011
    ..In contrast, complexation with the inhibitory antibody retards deuteration around the S2 site. Together, these studies reveal how S2 site exposure is promoted by receptor activation and suppressed by inhibitory antibodies...
  36. pmc Structural and mechanistic insights into cooperative assembly of dimeric Notch transcription complexes
    Kelly L Arnett
    Department of Cancer Biology, Dana Farber Cancer Institute, Boston, Massachusetts, USA
    Nat Struct Mol Biol 17:1312-7. 2010
    ..These studies reveal how promoter organizational features control cooperativity and, thus, the responsiveness of different promoters to Notch signaling...
  37. pmc Epstein-Barr virus exploits intrinsic B-lymphocyte transcription programs to achieve immortal cell growth
    Bo Zhao
    Department of Medicine, Brigham and Women s Hospital, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 108:14902-7. 2011
    ..The primed RBL program likely supports antigen-induced proliferation...
  38. pmc Complementary genomic screens identify SERCA as a therapeutic target in NOTCH1 mutated cancer
    Giovanni Roti
    Department of Pediatric Oncology, Dana Farber Cancer Institute, Boston, MA 02215, USA
    Cancer Cell 23:390-405. 2013
    ..These studies "credential" SERCA as a therapeutic target in cancers associated with NOTCH1 mutations...
  39. pmc Constitutive JAK3 activation induces lymphoproliferative syndromes in murine bone marrow transplantation models
    Melanie G Cornejo
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Blood 113:2746-54. 2009
    ..These data demonstrate that constitutive JAK3 activation disrupts T-cell homeostasis and induces lymphoproliferative diseases in mice...
  40. ncbi request reprint Aggressive Langerhans cell histiocytosis following T-ALL: clonally related neoplasms with persistent expression of constitutively active NOTCH1
    Scott J Rodig
    Department of Pathology, Brigham and Women s Hospital, Boston, Massachusetts, USA
    Am J Hematol 83:116-21. 2008
    ..Persistent expression of NOTCH1 in such tumors suggests that Notch pathway inhibitors could have a role in the treatment of these unusual neoplasms...
  41. pmc Dose-dependent induction of distinct phenotypic responses to Notch pathway activation in mammary epithelial cells
    Marco Mazzone
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 107:5012-7. 2010
    ..This unique feature of Notch signaling provides insights into mechanisms that contribute to the dichotomous effects of Notch during development and tumorigenesis...
  42. pmc Crosstalk between NOTCH and AKT signaling during murine megakaryocyte lineage specification
    Melanie G Cornejo
    Division of Hematology, Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA
    Blood 118:1264-73. 2011
    ....
  43. pmc Deletion-based mechanisms of Notch1 activation in T-ALL: key roles for RAG recombinase and a conserved internal translational start site in Notch1
    Todd D Ashworth
    Department of Pathology, Harvard Medical School, Boston, MA, USA
    Blood 116:5455-64. 2010
    ..Thus, like human T-ALL, murine T-ALL is often associated with acquired mutations that cause ligand-independent Notch1 activation...
  44. doi request reprint NUT rearrangement in undifferentiated carcinomas of the upper aerodigestive tract
    Edward B Stelow
    Department of Pathology, University of Virginia, Charlottesville, VA, USA
    Am J Surg Pathol 32:828-34. 2008
    ..The histologic features of these tumors are described in detail...
  45. pmc Modulation of gene expression via overlapping binding sites exerted by ZNF143, Notch1 and THAP11
    Richard Patryk Ngondo-Mbongo
    Architecture et Reactivite de l ARN, Universite de Strasbourg, CNRS, IBMC, 15 rue Rene Descartes, 67084 Strasbourg, France
    Nucleic Acids Res 41:4000-14. 2013
    ..Overall, our study establishes a novel relationship between ZNF143, THAP11 and ICN1 and reveals important insights into ZNF143-mediated gene regulation...
  46. pmc Cutaneous β-human papillomavirus E6 proteins bind Mastermind-like coactivators and repress Notch signaling
    Min Jie Alvin Tan
    Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 109:E1473-80. 2012
    ..These findings elucidate a mechanism of viral antagonism of Notch signaling, and suggest that Notch signaling is an important epithelial cell pathway target for the β-HPVs...
  47. ncbi request reprint Cloning of the t(1;5)(q23;q33) in a myeloproliferative disorder associated with eosinophilia: involvement of PDGFRB and response to imatinib
    Kathryn Wilkinson
    Dana Farber Cancer Institute, 44 Binney St, M514, Boston, MA 02115, USA
    Blood 102:4187-90. 2003
    ..Given the therapeutic implications, our findings stress the need to aggressively investigate the molecular basis of these diseases, with emphasis on the PDGFR family...
  48. ncbi request reprint Midline carcinoma of children and young adults with NUT rearrangement
    Christopher A French
    Department of Pathology, Brigham and Women s Hospital, 75 Francis St, Boston, MA 02115, USA
    J Clin Oncol 22:4135-9. 2004
    ..We sought to amass a more definitive series of tumors with NUT and/or BRD4 gene rearrangements and to determine distinct clinicopathologic features...
  49. ncbi request reprint Deregulated NOTCH signaling in acute T-cell lymphoblastic leukemia/lymphoma: new insights, questions, and opportunities
    Jon C Aster
    Department of Pathology, Brigham and Women s Hospital, Boston, MA 02115, USA
    Int J Hematol 82:295-301. 2005
    ..These insights raise a number of new questions relevant to T-ALL pathogenesis and offer exciting opportunities for rational targeted therapy...
  50. pmc Notch signaling specifies megakaryocyte development from hematopoietic stem cells
    Thomas Mercher
    Department of Medicine, Division of Hematology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 20115, USA
    Cell Stem Cell 3:314-26. 2008
    ..These findings indicate that Notch is a positive regulator of megakaryopoiesis and plays a more complex role in cell-fate decisions among myeloid progenitors than previously appreciated...
  51. ncbi request reprint SYK is a critical regulator of FLT3 in acute myeloid leukemia
    Alexandre Puissant
    Department of Pediatric Oncology, Dana Farber Cancer Institute and Boston Children s Hospital, Harvard Medical School, Boston, MA 02215, USA
    Cancer Cell 25:226-42. 2014
    ..In a FLT3-ITD in vivo model, SYK is indispensable for myeloproliferative disease (MPD) development, and SYK overexpression promotes overt transformation to AML and resistance to FLT3-ITD-targeted therapy...
  52. pmc Notch ligand delta-like 4 blockade attenuates atherosclerosis and metabolic disorders
    Daiju Fukuda
    Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 109:E1868-77. 2012
    ..Furthermore, Dll4 skewed macrophages toward a proinflammatory phenotype ("M1"). These results suggest that Dll4-Notch signaling plays a central role in the shared mechanism for the pathogenesis of cardiometabolic disorders...
  53. pmc Functional screening identifies CRLF2 in precursor B-cell acute lymphoblastic leukemia
    Akinori Yoda
    Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 107:252-7. 2010
    ..Together, these findings implicate CRLF2 as an important factor in B-ALL with diagnostic, prognostic, and therapeutic implications...
  54. ncbi request reprint The multifaceted role of Notch in cancer
    Monideepa Roy
    Department of Pathology, Brigham and Women s Hospital, 75 Francis Street, Boston, MA 02115, USA
    Curr Opin Genet Dev 17:52-9. 2007
    ....
  55. ncbi request reprint Delta-like 4 induces notch signaling in macrophages: implications for inflammation
    Erik Fung
    Center for Excellence in Vascular Biology, Brigham and Women s Hospital, Harvard Medical School, 77 Ave Louis Pasteur, Boston, MA 02115, USA
    Circulation 115:2948-56. 2007
    ..Activated macrophages contribute to the pathogenesis of inflammatory diseases such as atherosclerosis. Although Notch signaling participates in various aspects of immunity, its role in macrophage activation remains undetermined...
  56. pmc Notch signalling in T-cell lymphoblastic leukaemia/lymphoma and other haematological malignancies
    Jon C Aster
    Department of Pathology, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Pathol 223:262-73. 2011
    ..Here, we review the role of Notch signalling in various blood cancers, focusing on T-LL with an eye towards targeted therapeutics...
  57. ncbi request reprint BRAF mutations are sufficient to promote nevi formation and cooperate with p53 in the genesis of melanoma
    E Elizabeth Patton
    Howard Hughes Medical Institute, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA
    Curr Biol 15:249-54. 2005
    ....
  58. ncbi request reprint Multiple niches for Notch in cancer: context is everything
    Andrew P Weng
    Department of Pathology, Brigham and Women s Hospital, 75 Francis Street, Boston, MA 02115, USA
    Curr Opin Genet Dev 14:48-54. 2004
    ..In addition, several viral oncoproteins and chromosomal translocations target one or more components of a Notch transcriptional activation complex...
  59. ncbi request reprint No T without D3: a critical role for cyclin D3 in normal and malignant precursor T cells
    Andrew P Weng
    Department of Pathology, Brigham and Women s Hospital, Boston, MA 02115, USA
    Cancer Cell 4:417-8. 2003
    ..A definitive knockout reported in this issue of Cancer Cell by Sicinska et al. reveals an unsuspected role for cyclin D3 in normal T cell development and suggests new therapeutic possibilities in precursor T cell leukemia...
  60. doi request reprint In brief: Notch signalling in health and disease
    Jon C Aster
    Department of Pathology, Brigham and Women s Hospital, Boston, MA, USA
    J Pathol 232:1-3. 2014
    ..Notch dysregulation is also important in cardiovascular disease and disorders of immunity. This mini-review outlines key features of the Notch signalling pathway and emerging data linking it to human diseases...
  61. ncbi request reprint Functional diversity of notch family genes in fetal lung development
    Yanping Kong
    Brigham and Women s Hospital, Dept of Pathology, 75 Francis St, Boston, MA 02115, USA
    Am J Physiol Lung Cell Mol Physiol 286:L1075-83. 2004
    ..Cumulatively, these observations suggest that interactions between distinct Notch family members can have diverse tissue-specific regulatory functions during development, arguing against simple functional redundancy...
  62. ncbi request reprint JAGGED1 expression is associated with prostate cancer metastasis and recurrence
    Sandro Santagata
    Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cancer Res 64:6854-7. 2004
    ....
  63. pmc Molecular evidence for rhesus lymphocryptovirus infection of epithelial cells in immunosuppressed rhesus macaques
    Jeffery L Kutok
    Department of Pathology, BrighamWomen s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Virol 78:3455-61. 2004
    ..These studies demonstrate that the rhesus LCV has tropism for epithelial cells, in addition to B cells, and is a relevant animal model system for studying the role of epithelial cell infection in EBV pathogenesis...
  64. pmc A zebrafish bmyb mutation causes genome instability and increased cancer susceptibility
    Jennifer L Shepard
    Children s Hospital, 300 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 102:13194-9. 2005
    ..Our findings show that zebrafish screens can uncover cancer pathways, and demonstrate that loss of function of bmyb is associated with cancer...
  65. pmc c-Myc is an important direct target of Notch1 in T-cell acute lymphoblastic leukemia/lymphoma
    Andrew P Weng
    Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
    Genes Dev 20:2096-109. 2006
    ..Together, these data implicate c-myc as a developmentally regulated direct downstream target of Notch1 that contributes to the growth of T-ALL cells...
  66. pmc Growth suppression of pre-T acute lymphoblastic leukemia cells by inhibition of notch signaling
    Andrew P Weng
    Departments of Pathology, Brigham and Women s Hospital, Harvard Medical School Department of Adult Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Mol Cell Biol 23:655-64. 2003
    ....
  67. pmc Plasma organochlorine levels and risk of non-Hodgkin lymphoma in a cohort of men
    Kimberly A Bertrand
    Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA
    Epidemiology 21:172-80. 2010
    ..Environmental exposure to polychlorinated biphenyls (PCBs) and p,p'-dichlorodiphenyldichloroethylene (p, p'-DDE) has been associated with the risk of non-Hodgkin lymphoma...
  68. ncbi request reprint Notch signaling as a therapeutic target
    Yunsun Nam
    Department of Pathology, Brigham and Women s Hospital and Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA
    Curr Opin Chem Biol 6:501-9. 2002
    ..These advances offer a variety of potential avenues to manipulate Notch signaling for therapeutic purposes in the treatment of cancer and in stem cell maintenance...
  69. ncbi request reprint Diffuse large B-cell lymphoma outcome prediction by gene-expression profiling and supervised machine learning
    Margaret A Shipp
    Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA
    Nat Med 8:68-74. 2002
    ..Our data indicate that supervised learning classification techniques can predict outcome in DLBCL and identify rational targets for intervention...
  70. pmc Detection of BCL2 rearrangements in follicular lymphoma
    Jon C Aster
    Department of Pathology, Brigham and Women s Hospital, Boston, Massachusetts 02420, USA
    Am J Pathol 160:759-63. 2002
  71. ncbi request reprint Notch oncoproteins depend on gamma-secretase/presenilin activity for processing and function
    Indranil Das
    Department of Pathology and Obstetrics Gynecology, Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA
    J Biol Chem 279:30771-80. 2004
    ..These studies highlight potential uses and limitations of gamma-secretase/presenilin inhibitors in targeted therapy of Notch-related neoplasms...
  72. ncbi request reprint Notch signaling controls the generation and differentiation of early T lineage progenitors
    Arivazhagan Sambandam
    Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Nat Immunol 6:663-70. 2005
    ..In contrast, multipotent hematopoietic progenitors circulated in the blood even in the absence of Notch signaling, suggesting that critical Notch signals during early T lineage development are delivered early after thymic entry...
  73. ncbi request reprint Deltex1 redirects lymphoid progenitors to the B cell lineage by antagonizing Notch1
    David J Izon
    Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, PA 19104, USA
    Immunity 16:231-43. 2002
    ..These data suggest that a balance of inductive Notch1 signals and inhibitory signals mediated through Deltex1 and other modulators regulate T-B lineage commitment...
  74. ncbi request reprint Notch signaling in cancer
    Eric J Allenspach
    Departments of Pathology and Laboratory Medicine, Institute for Medicine and Engineering, Abramson Family Cancer Research Institute, University of Pennsylvania, 421 Curie Boulevard, Philadelphia, PA 19104, USA
    Cancer Biol Ther 1:466-76. 2002
    ..Then, we critically review literature pertaining to the role of Notch signaling in several cancers, and discuss possible therapeutic targets in the Notch pathway...
  75. ncbi request reprint Notch signaling in hematopoiesis and early lymphocyte development
    David Allman
    Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, PA 19104 6160, USA
    Immunol Rev 187:75-86. 2002
    ..In committed progenitors, Notch signaling plays a key role in determining lymphoid cell fates. This review focuses on recent developments to understand the role of Notch signaling in early events in hematopoiesis...
  76. ncbi request reprint Activation of Notch-1 signaling maintains the neoplastic phenotype in human Ras-transformed cells
    Sanne Weijzen
    Cancer Immunology Program, Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, Illinois, USA
    Nat Med 8:979-86. 2002
    ..These observations place Notch signaling among key downstream effectors of oncogenic Ras and suggest that it might be a novel therapeutic target...
  77. pmc NOTCH1 directly regulates c-MYC and activates a feed-forward-loop transcriptional network promoting leukemic cell growth
    Teresa Palomero
    Institute for Cancer Genetics and Joint Centers for Systems Biology, Columbia University, New York, NY 10032, USA
    Proc Natl Acad Sci U S A 103:18261-6. 2006
    ..These results identify c-MYC as an essential mediator of NOTCH1 signaling and integrate NOTCH1 activation with oncogenic signaling pathways upstream of c-MYC...
  78. ncbi request reprint An invitation to T and more: notch signaling in lymphopoiesis
    David Allman
    Department of Pathology and Laboratory Medicine, The Abramson Family Cancer Research Institute, University of Pennsylvania Medical Center, Philadelphia 19104, USA
    Cell 109:S1-11. 2002
    ..During lymphoid development, Notch influences a series of cell fate decisions involving multipotent progenitors. This review focuses on current views and lingering uncertainties about Notch function in lymphoid cells...
  79. ncbi request reprint Mastermind critically regulates Notch-mediated lymphoid cell fate decisions
    Ivan Maillard
    Division of Hematology Oncology, Abramson Family Cancer Research Institute, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104 6160, USA
    Blood 104:1696-702. 2004
    ..These results suggest a critical role for MAMLs during Notch-mediated cell fate decisions in vivo and indicate that DNMAML1, but not Deltex1, can be used to interfere with the function of multiple Notch family members...
  80. ncbi request reprint T cell acute lymphoblastic leukemia/lymphoma: a human cancer commonly associated with aberrant NOTCH1 signaling
    Warren S Pear
    Abramson Center Cancer Research Institute, Institute for Medicine and Engineering and Department of Pathology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    Curr Opin Hematol 11:426-33. 2004
    ..This picture has changed dramatically in the past year with the discovery of frequent mutations involving NOTCH1 in human T cell acute lymphoblastic leukemia/lymphoma...
  81. pmc Notch signaling is a potent inducer of growth arrest and apoptosis in a wide range of B-cell malignancies
    Patrick A Zweidler-McKay
    Department of Pathology and Laboratory Medicine, University of Pennsylvania, 611 BRB II III, 421 Curie Blvd, Philadelphia, PA 19104 6160, USA
    Blood 106:3898-906. 2005
    ..These results suggest that therapies capable of activating Notch/Hes1 signaling may have therapeutic potential in a wide range of human B-cell malignancies...
  82. pmc Notch signals positively regulate activity of the mTOR pathway in T-cell acute lymphoblastic leukemia
    Steven M Chan
    Division of Immunology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
    Blood 110:278-86. 2007
    ..T-ALL cell growth was suppressed in a highly synergistic manner by simultaneous treatment with the mTOR inhibitor rapamycin and GSI, which represents a rational drug combination for treating this aggressive human malignancy...
  83. pmc Tribbles homolog 2 inactivates C/EBPalpha and causes acute myelogenous leukemia
    Karen Keeshan
    Department of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Cancer Cell 10:401-11. 2006
    ..Furthermore, Trib2 expression was elevated in a subset of human AML patient samples. Together, our data identify Trib2 as an oncogene that induces AML through a mechanism involving inactivation of C/EBPalpha...
  84. pmc Identification of a conserved negative regulatory sequence that influences the leukemogenic activity of NOTCH1
    Mark Y Chiang
    Department of Hematology Oncology, Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Mol Cell Biol 26:6261-71. 2006
    ..These studies indicate that S4 is an important negative regulatory sequence and that the deletion of S4 likely contributes to the development of human T-ALL...
  85. pmc Inactivation of the PRDM1/BLIMP1 gene in diffuse large B cell lymphoma
    Laura Pasqualucci
    Institute for Cancer Genetics and 2The Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY 10032, USA
    J Exp Med 203:311-7. 2006
    ..These findings point to a role for BLIMP1 as a tumor suppressor gene, whose inactivation may contribute to lymphomagenesis by blocking post-GC differentiation of B cells toward plasma cells...
  86. ncbi request reprint Lack of IKBA coding region mutations in primary mediastinal large B-cell lymphoma and the host response subtype of diffuse large B-cell lymphoma
    Hidenobu Takahashi
    Blood 107:844-5. 2006
  87. ncbi request reprint Alpha E beta 7 (CD103) expression identifies a highly active, tonsil-resident effector-memory CTL population
    Tonia Woodberry
    Partners AIDS Research Center, Massachusetts General Hospital, Boston 02129, USA
    J Immunol 175:4355-62. 2005
    ....
  88. ncbi request reprint Molecular profiling of diffuse large B-cell lymphoma identifies robust subtypes including one characterized by host inflammatory response
    Stefano Monti
    The Broad Institute, Cambridge, MA, USA
    Blood 105:1851-61. 2005
    ..These studies identify tumor microenvironment and host inflammatory response as defining features in DLBCL and suggest rational treatment targets in specific DLBCL subsets...
  89. pmc Canonical notch signaling is dispensable for the maintenance of adult hematopoietic stem cells
    Ivan Maillard
    Center for Stem Cell Biology, Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA
    Cell Stem Cell 2:356-66. 2008
    ..Furthermore, Notch target genes were expressed at low levels in primitive hematopoietic progenitors. Taken together, these results rule out an essential physiological role for cell-autonomous canonical Notch signals in HSC maintenance...