Research Topics
Species | Jon AsterSummaryAffiliation: Harvard University Country: USA Publications
Research Grants
| Collaborators
|
Detail Information
Publications
Diffuse large B-cell lymphoma outcome prediction by gene-expression profiling and supervised machine learningMargaret 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...
Notch ankyrin repeat domain variation influences leukemogenesis and Myc transactivationJon C Aster
Department of Pathology, Brigham and Women s Hospital, Boston, Massachusetts, United States of America
PLoS ONE 6:e25645. 2011....- Detection of BCL2 rearrangements in follicular lymphomaJon C Aster
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts 02420, USA
Am J Pathol 160:759-63. 2002 - Notch signalling in T-cell lymphoblastic leukaemia/lymphoma and other haematological malignanciesJon 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... - Deregulated NOTCH signaling in acute T-cell lymphoblastic leukemia/lymphoma: new insights, questions, and opportunitiesJon 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... - EBNA-3B- and EBNA-3C-regulated cellular genes in Epstein-Barr virus-immortalized lymphoblastoid cell linesAdrienne Chen
Channing Laboratory, 181 Longwood Avenue, Boston, MA 02115, USA
J Virol 80:10139-50. 2006.... - Plasma organochlorine levels and risk of non-Hodgkin lymphoma in a cohort of menKimberly 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... - Plasma organochlorine levels and risk of non-Hodgkin lymphoma in the Nurses' Health StudyFrancine 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... - A prospective study of Epstein-Barr virus antibodies and risk of non-Hodgkin lymphomaKimberly 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... 
Notch signaling specifies megakaryocyte development from hematopoietic stem cellsThomas 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...- 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 subtypesHidenobu Takahashi
Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
Clin Cancer Res 12:3265-71. 2006.... - 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 lymphomaKerry 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... - Cooperative assembly of higher-order Notch complexes functions as a switch to induce transcriptionYunsun 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.... - Notch-1 regulates pulmonary neuroendocrine cell differentiation in cell lines and in transgenic miceLin 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... - NFkappaB activity, function, and target-gene signatures in primary mediastinal large B-cell lymphoma and diffuse large B-cell lymphoma subtypesFriedrich 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... - The Tel-Abl (ETV6-Abl) tyrosine kinase, product of complex (9;12) translocations in human leukemia, induces distinct myeloproliferative disease in miceRyan P Million
The Center for Blood Research and Department of Genetics, Brigham and Women's Hospital, Harvard Institutes of Medicine, Boston, MA 02115, USA
Blood 99:4568-77. 2002..These results show that Tel-Abl has leukemogenic properties from distinct from those of Bcr-Abl and may act in a different bone marrow progenitor... - Notch subunit heterodimerization and prevention of ligand-independent proteolytic activation depend, respectively, on a novel domain and the LNR repeatsCheryll 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... - Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemiaAndrew 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... - Leukemia-associated mutations within the NOTCH1 heterodimerization domain fall into at least two distinct mechanistic classesMichael 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... - Aggressive Langerhans cell histiocytosis following T-ALL: clonally related neoplasms with persistent expression of constitutively active NOTCH1Scott 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... - Experimental rhesus lymphocryptovirus infection in immunosuppressed macaques: an animal model for Epstein-Barr virus pathogenesis in the immunosuppressed hostPierre 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... - Delta-like 4 induces notch signaling in macrophages: implications for inflammationErik 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... - Effects of S1 cleavage on the structure, surface export, and signaling activity of human Notch1 and Notch2Wendy 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.... - Growth suppression of pre-T acute lymphoblastic leukemia cells by inhibition of notch signalingAndrew 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.... - Myc-induced T cell leukemia in transgenic zebrafishDavid 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... - Structural basis for cooperativity in recruitment of MAML coactivators to Notch transcription complexesYunsun 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... - No T without D3: a critical role for cyclin D3 in normal and malignant precursor T cellsAndrew 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... - Notch signaling in leukemiaJon 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... - Functional screening identifies CRLF2 in precursor B-cell acute lymphoblastic leukemiaAkinori 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... - Novel SSBP2-JAK2 fusion gene resulting from a t(5;9)(q14.1;p24.1) in pre-B acute lymphocytic leukemiaJennifer 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... - Dose-dependent induction of distinct phenotypic responses to Notch pathway activation in mammary epithelial cellsMarco 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... - Mutational and energetic studies of Notch 1 transcription complexesCristina 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.... - Molecular evidence for rhesus lymphocryptovirus infection of epithelial cells in immunosuppressed rhesus macaquesJeffery 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... - Molecular biology of anaplastic lymphoma kinase-positive anaplastic large-cell lymphomaJeffery L Kutok
Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA
J Clin Oncol 20:3691-702. 2002..The unique molecular pathogenesis of ALK+ ALCL is likely to lead to novel therapeutic approaches directed at specific inhibition of ALK or downstream effectors... - Cloning of the t(1;5)(q23;q33) in a myeloproliferative disorder associated with eosinophilia: involvement of PDGFRB and response to imatinibKathryn 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... - Structural requirements for assembly of the CSL.intracellular Notch1.Mastermind-like 1 transcriptional activation complexYunsun 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... - The BAL-binding protein BBAP and related Deltex family members exhibit ubiquitin-protein isopeptide ligase activityKunihiko 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... - Nuclear magnetic resonance structure of a prototype Lin12-Notch repeat module from human Notch1Didem 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... - JAGGED1 expression is associated with prostate cancer metastasis and recurrenceSandro Santagata
Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
Cancer Res 64:6854-7. 2004.... - Midline carcinoma of children and young adults with NUT rearrangementChristopher 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... - Deltex1 redirects lymphoid progenitors to the B cell lineage by antagonizing Notch1David 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... - NOTCH1 directly regulates c-MYC and activates a feed-forward-loop transcriptional network promoting leukemic cell growthTeresa 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... - Molecular profiling of diffuse large B-cell lymphoma identifies robust subtypes including one characterized by host inflammatory responseStefano 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... - Phase II study of enzastaurin, a protein kinase C beta inhibitor, in patients with relapsed or refractory diffuse large B-cell lymphomaMichael J Robertson
Indiana University Medical Center, Indianapolis, IN, USA
J Clin Oncol 25:1741-6. 2007..We conducted a multicenter phase II study of a potent inhibitor of PKCbeta, enzastaurin, in patients with relapsed or refractory DLBCL... - An invitation to T and more: notch signaling in lymphopoiesisDavid 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... - Activation of Notch-1 signaling maintains the neoplastic phenotype in human Ras-transformed cellsSanne 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... - Lack of IKBA coding region mutations in primary mediastinal large B-cell lymphoma and the host response subtype of diffuse large B-cell lymphomaHidenobu Takahashi
Blood 107:844-5. 2006 - Notch signaling in cancerEric 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... - Identification of a conserved negative regulatory sequence that influences the leukemogenic activity of NOTCH1Mark 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... - Notch signaling controls the generation and differentiation of early T lineage progenitorsArivazhagan 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... - Notch signaling is a potent inducer of growth arrest and apoptosis in a wide range of B-cell malignanciesPatrick 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... - Notch signaling in hematopoiesis and early lymphocyte developmentDavid 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... - Canonical notch signaling is dispensable for the maintenance of adult hematopoietic stem cellsIvan 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... - F3/contactin acts as a functional ligand for Notch during oligodendrocyte maturationQi 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... - Tribbles homolog 2 inactivates C/EBPalpha and causes acute myelogenous leukemiaKaren 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... - Mastermind critically regulates Notch-mediated lymphoid cell fate decisionsIvan 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... - Inactivation of the PRDM1/BLIMP1 gene in diffuse large B cell lymphomaLaura 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...
Research Grants
- Pathogenesis of Notch LeukemiaJon Aster; Fiscal Year: 2007..1. To identify domains of MAML1 that are essential for function in normal and transformed lymphoid cells 3.2. To identify and characterize small molecule inhibitors of CSL/ICN/MAML1 function ..
- PATHOGENESIS OF NOTCH 1 LEUKEMIAJon Aster; Fiscal Year: 2002..These studies will lead to an improved understanding of how Notch1 causes leukemic transformation, and may identify new therapeutic targets. ..