Marshall S Horwitz

Summary

Affiliation: University of Washington
Country: USA

Publications

  1. pmc Integrative analysis of RUNX1 downstream pathways and target genes
    Joelle Michaud
    Molecular Medicine Division, The Walter and Eliza Hall Institute of Medical Research, Parkville 3050, Victoria, Australia
    BMC Genomics 9:363. 2008
  2. pmc Anticipation in familial leukemia
    M Horwitz
    Division of Medical Genetics, School of Medicine, University of Washington, Seattle 98195, USA
    Am J Hum Genet 59:990-8. 1996
  3. ncbi request reprint Leukemia in severe congenital neutropenia: defective proteolysis suggests new pathways to malignancy and opportunities for therapy
    Marshall Horwitz
    Division of Medical Genetics, Department of Medicine, University of Washington School of Medicine, 1705 NE Pacific Street, HSB K236B, Seattle, WA 98195 7720, USA
    Cancer Invest 21:579-87. 2003
  4. pmc Neutrophil elastase in cyclic and severe congenital neutropenia
    Marshall S Horwitz
    Division of Medical Genetics, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA
    Blood 109:1817-24. 2007
  5. ncbi request reprint Role of neutrophil elastase in bone marrow failure syndromes: molecular genetic revival of the chalone hypothesis
    Marshall Horwitz
    Division of Medical Genetics, Department of Medicine, University of Washington School of Medicine, Seattle 98195, USA
    Curr Opin Hematol 10:49-54. 2003
  6. pmc Genetic heterogeneity in familial acute myelogenous leukemia: evidence for a second locus at chromosome 16q21-23.2
    M Horwitz
    Markey Molecular Medicine Center, and Department of Medicine, School of Medicine, University of Washington, Seattle 98195, USA
    Am J Hum Genet 61:873-81. 1997
  7. ncbi request reprint Mutations in ELA2, encoding neutrophil elastase, define a 21-day biological clock in cyclic haematopoiesis
    M Horwitz
    Division of Medical Genetics, University of Washington School of Medicine, Seattle, Washington, USA
    Nat Genet 23:433-6. 1999
  8. pmc Pseudoautosomal linkage of Hodgkin disease
    M Horwitz
    Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA, USA
    Am J Hum Genet 65:1413-22. 1999
  9. pmc Contributions to neutropenia from PFAAP5 (N4BP2L2), a novel protein mediating transcriptional repressor cooperation between Gfi1 and neutrophil elastase
    Stephen J Salipante
    Department of Genome Sciences, University of Washington, Box 355065, Seattle, WA 98195, USA
    Mol Cell Biol 29:4394-405. 2009
  10. pmc The kelch protein KLHDC8B guards against mitotic errors, centrosomal amplification, and chromosomal instability
    Maxwell M Krem
    Department of Pathology and the Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, Washington 98109, USA
    J Biol Chem 287:39083-93. 2012

Research Grants

  1. Genomic Fate Maps
    Marshall S Horwitz; Fiscal Year: 2010
  2. Molecular Genetic Basic of Cyclic Hematopiesis
    Marshall S Horwitz; Fiscal Year: 2010
  3. Mistargeting of Elastase in Bone Marrow Failure
    Marshall Horwitz; Fiscal Year: 2007
  4. Molecular Genetic Basic of Cyclic Hematopiesis
    Marshall Horwitz; Fiscal Year: 2007
  5. MEDICAL GENETICS POSTDOCTORAL FELLOWSHIP
    Marshall Horwitz; Fiscal Year: 2007
  6. MOLECULAR GENETIC BASIS OF CYCLIC HEMATOPOIESIS
    Marshall Horwitz; Fiscal Year: 2006
  7. Genomic Fate Maps
    Marshall S Horwitz; Fiscal Year: 2010

Collaborators

Detail Information

Publications42

  1. pmc Integrative analysis of RUNX1 downstream pathways and target genes
    Joelle Michaud
    Molecular Medicine Division, The Walter and Eliza Hall Institute of Medical Research, Parkville 3050, Victoria, Australia
    BMC Genomics 9:363. 2008
    ..We have used multiple microarray platforms and bioinformatic techniques to help identify these biological pathways to aid in the understanding of why RUNX1 mutations lead to leukemia...
  2. pmc Anticipation in familial leukemia
    M Horwitz
    Division of Medical Genetics, School of Medicine, University of Washington, Seattle 98195, USA
    Am J Hum Genet 59:990-8. 1996
    ..We speculate on three possible candidate genes for familial leukemia with anticipation: a locus on 21q22.1-22.2, CBL2 on 11q23.3, and CBFB or a nearby gene on 16q22...
  3. ncbi request reprint Leukemia in severe congenital neutropenia: defective proteolysis suggests new pathways to malignancy and opportunities for therapy
    Marshall Horwitz
    Division of Medical Genetics, Department of Medicine, University of Washington School of Medicine, 1705 NE Pacific Street, HSB K236B, Seattle, WA 98195 7720, USA
    Cancer Invest 21:579-87. 2003
    ..Continued elucidation of the clinical features, molecular genetics, and biochemistry is likely to provide insight into novel pathways of leukemia induction with attendant prospects for new avenues of therapy...
  4. pmc Neutrophil elastase in cyclic and severe congenital neutropenia
    Marshall S Horwitz
    Division of Medical Genetics, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA
    Blood 109:1817-24. 2007
    ..Nevertheless, mutations in all 3 genes are capable of causing the mislocalization of NE and may also induce the unfolded protein response, suggesting that there might a convergent pathogenic mechanism focusing on NE...
  5. ncbi request reprint Role of neutrophil elastase in bone marrow failure syndromes: molecular genetic revival of the chalone hypothesis
    Marshall Horwitz
    Division of Medical Genetics, Department of Medicine, University of Washington School of Medicine, Seattle 98195, USA
    Curr Opin Hematol 10:49-54. 2003
    ..The authors propose that neutrophil elastase acts as an inhibitor of myelopoiesis, substantiating a chalone hypothesis proposed many years ago...
  6. pmc Genetic heterogeneity in familial acute myelogenous leukemia: evidence for a second locus at chromosome 16q21-23.2
    M Horwitz
    Markey Molecular Medicine Center, and Department of Medicine, School of Medicine, University of Washington, Seattle 98195, USA
    Am J Hum Genet 61:873-81. 1997
    ..The "repeat expansion detection" method, capable of detecting dynamic mutation associated with anticipation, more generally excludes large CAG repeat expansion as a cause of leukemia in this family...
  7. ncbi request reprint Mutations in ELA2, encoding neutrophil elastase, define a 21-day biological clock in cyclic haematopoiesis
    M Horwitz
    Division of Medical Genetics, University of Washington School of Medicine, Seattle, Washington, USA
    Nat Genet 23:433-6. 1999
    ..We hypothesize that a perturbed interaction between neutrophil elastase and serpins or other substrates may regulate mechanisms governing the clock-like timing of haematopoiesis...
  8. pmc Pseudoautosomal linkage of Hodgkin disease
    M Horwitz
    Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA, USA
    Am J Hum Genet 65:1413-22. 1999
    ..00. The resulting beta values indicate that the putative PAR- and HLA-linked loci account for 29% and 40%, respectively, of the heritability of HD in an American population...
  9. pmc Contributions to neutropenia from PFAAP5 (N4BP2L2), a novel protein mediating transcriptional repressor cooperation between Gfi1 and neutrophil elastase
    Stephen J Salipante
    Department of Genome Sciences, University of Washington, Box 355065, Seattle, WA 98195, USA
    Mol Cell Biol 29:4394-405. 2009
    ....
  10. pmc The kelch protein KLHDC8B guards against mitotic errors, centrosomal amplification, and chromosomal instability
    Maxwell M Krem
    Department of Pathology and the Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, Washington 98109, USA
    J Biol Chem 287:39083-93. 2012
    ..The significant impact of KLHDC8B implicates the central roles of mitotic regulation and chromosomal segregation in the pathogenesis of HL and provides a novel molecular mechanism for chromosomal instability in HL...
  11. pmc Decoding cell lineage from acquired mutations using arbitrary deep sequencing
    Cheryl A Carlson
    Department of Pathology, University of Washington School of Medicine, Seattle, Washington, USA
    Nat Methods 9:78-80. 2012
    ..This study helps pave the way toward construction of retrospective cell-fate maps based on mutations accumulating in genomes of somatic cells...
  12. ncbi request reprint Double de novo mutations of ELA2 in cyclic and severe congenital neutropenia
    Stephen J Salipante
    Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA
    Hum Mutat 28:874-81. 2007
    ....
  13. ncbi request reprint Mutations in a gene encoding a midbody protein in binucleated Reed-Sternberg cells of Hodgkin lymphoma
    Maxwell M Krem
    Medical Oncology Program, Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA
    Cell Cycle 9:670-5. 2010
    ..Midbody components may be an overlooked source of tumor suppressor genes...
  14. pmc Epigenetic regulation of protein-coding and microRNA genes by the Gfi1-interacting tumor suppressor PRDM5
    Zhijun Duan
    Division of Medical Genetics, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA
    Mol Cell Biol 27:6889-902. 2007
    ..In neutropenic patients, we identified PRDM5 protein sequence variants perturbing transcriptional function, suggesting a potentially important role in hematopoiesis...
  15. pmc ELANE mutations in cyclic and severe congenital neutropenia: genetics and pathophysiology
    Marshall S Horwitz
    Department of Pathology, University of Washington School of Medicine, 850 Republican Street, Seattle, WA 98109, USA
    Hematol Oncol Clin North Am 27:19-41, vii. 2013
    ..SCN is genetically heterogeneous but is most frequently associated with ELANE mutations. We discuss how the mutations provide clues into the pathogenesis of neutropenia and describe current hypotheses for its molecular mechanisms...
  16. pmc Use of somatic mutations to quantify random contributions to mouse development
    Wenyu Zhou
    Department of Pathology, University of Washington, Box 358056, Seattle, WA 98195, USA
    BMC Genomics 14:39. 2013
    ..Consequently, a single defined cell fate map applicable to all individuals cannot exist...
  17. pmc Clonal expansions in ulcerative colitis identify patients with neoplasia
    Jesse J Salk
    Department of Pathology, University of Washington School of Medicine, Seattle, WA 98105, USA
    Proc Natl Acad Sci U S A 106:20871-6. 2009
    ....
  18. pmc Phylogenetic analysis of developmental and postnatal mouse cell lineages
    Stephen J Salipante
    Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98109, USA
    Evol Dev 12:84-94. 2010
    ..This work offers a longitudinal study of developmental lineages, from conception to adulthood, and provides insight into basic questions of mouse embryology as well as the somatic processes that occur after birth...
  19. pmc Mutations in a gene encoding a midbody kelch protein in familial and sporadic classical Hodgkin lymphoma lead to binucleated cells
    Stephen J Salipante
    Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA
    Proc Natl Acad Sci U S A 106:14920-5. 2009
    ..Depletion of KLHDC8B through RNA interference leads to an increase in binucleated cells, implicating its reduced expression in the formation of cHL's signature RS cell...
  20. pmc Mutations in proto-oncogene GFI1 cause human neutropenia and target ELA2
    Richard E Person
    Department of Pathology, University of Washington School of Medicine, Box 357720, Seattle, Washington 98195, USA
    Nat Genet 34:308-12. 2003
    ....
  21. ncbi request reprint Gfi-1 oncoproteins in hematopoiesis
    Zhijun Duan
    Department of Medicine, University of Washington School of Medicine, Seattle 98195 7720, USA
    Hematology 8:339-44. 2003
    ..The ongoing identification of repressed target genes and interacting transcriptional cofactors is helping to unravel the central contributions of these two hematopoietic factors...
  22. doi request reprint Support for the N-methyl-D-aspartate receptor hypofunction hypothesis of schizophrenia from exome sequencing in multiplex families
    Andrew E Timms
    Department of Pathology, University of Washington School of Medicine, Seattle, USA
    JAMA Psychiatry 70:582-90. 2013
    ..Investigation of genetic forms of schizophrenia will lead to a better understanding of the underlying molecular pathways, which will then enable targeted approaches for disease prevention and treatment...
  23. ncbi request reprint A phylogenetic approach to mapping cell fate
    Stephen J Salipante
    Department of Genome Sciences, University of Washington School of Medicine, Seattle, Washington 98195, USA
    Curr Top Dev Biol 79:157-84. 2007
    ....
  24. pmc Phylogenetic fate mapping: theoretical and experimental studies applied to the development of mouse fibroblasts
    Stephen J Salipante
    Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA
    Genetics 178:967-77. 2008
    ....
  25. ncbi request reprint Mice expressing a neutrophil elastase mutation derived from patients with severe congenital neutropenia have normal granulopoiesis
    David S Grenda
    Division of Oncology, Department of Medicine, Washington University School of Medicine, 660 S Euclid Avenue, St Louis, MO 63110, USA
    Blood 100:3221-8. 2002
    ..To date, no cases of leukemia have been detected. Collectively, these data suggest that expression of V72M NE is not sufficient to induce an SCN phenotype or leukemia in mice...
  26. pmc A novel notch protein, N2N, targeted by neutrophil elastase and implicated in hereditary neutropenia
    Zhijun Duan
    Division of Medical Genetics, Department of Medicine, University of Washington School of Medicine, Seattle, Washington 98195, USA
    Mol Cell Biol 24:58-70. 2004
    ....
  27. ncbi request reprint Hereditary neutropenia: dogs explain human neutrophil elastase mutations
    Marshall Horwitz
    Division of Medical Genetics Department of Medicine, University of Washington School of Medicine, 1705 NE Pacific Street, HSB K236B, Box 357720 Seattle, WA 98195, USA
    Trends Mol Med 10:163-70. 2004
    ....
  28. ncbi request reprint Mutations associated with neutropenia in dogs and humans disrupt intracellular transport of neutrophil elastase
    Kathleen F Benson
    Division of Medical Genetics Department of Medicine, University of Washington School of Medicine, Box 357720, 1705 NE Pacific Street, HSB K236B, Seattle, Washington 98195, USA
    Nat Genet 35:90-6. 2003
    ..Most mutations in ELA2 that cause human cyclic hematopoiesis prevent membrane localization of neutrophil elastase, whereas most mutations in ELA2 that cause SCN lead to exclusive membrane localization...
  29. ncbi request reprint Lymphoid enhancer factor-1 links two hereditary leukemia syndromes through core-binding factor alpha regulation of ELA2
    Feng Qian Li
    Department of Medicine, Howard Hughes Medical Institute, University of Washington School of Medicine, Seattle, Washington 98195 7720, USA
    J Biol Chem 279:2873-84. 2004
    ..Two hereditary AML predisposition syndromes may therefore intersect via LEF-1, potentially linking them to more generalized cancer mechanisms...
  30. ncbi request reprint Gfi-1 takes center stage in hematopoietic stem cells
    Zhijun Duan
    Division of Medical Genetics Department of Medicine, University of Washington School of Medicine, 1705 NE Pacific Street, HSB K236B, Box 357720, Seattle, WA 98195, USA
    Trends Mol Med 11:49-52. 2005
    ....
  31. pmc Gfi1 coordinates epigenetic repression of p21Cip/WAF1 by recruitment of histone lysine methyltransferase G9a and histone deacetylase 1
    Zhijun Duan
    Division of Medical Genetics, Department of Medicine, University of Washington School of Medicine, Box 357720, Seattle, WA 98195, USA
    Mol Cell Biol 25:10338-51. 2005
    ..Silencing of Gfi1 expression in myeloid cells reverses G9a and HDAC1 recruitment to p21Cip/WAF1 and elevates its expression. These findings highlight the role of epigenetics in the regulation of development and oncogenesis by Gfi1...
  32. pmc HIF1α induced switch from bivalent to exclusively glycolytic metabolism during ESC-to-EpiSC/hESC transition
    Wenyu Zhou
    H Ruohola Baker Department of Biology, University of Washington, Seattle, WA, USA
    EMBO J 31:2103-16. 2012
    ..This metabolic switch during early stem-cell development may be deterministic...
  33. pmc Passenger mutations as a marker of clonal cell lineages in emerging neoplasia
    Jesse J Salk
    Department of Pathology, University of Washington School of Medicine MB 357705, 1959 NE Pacific St, Seattle, WA 98195, United States
    Semin Cancer Biol 20:294-303. 2010
    ..We discuss historical as well as contemporary approaches and consider ways in which powerful new genomic technologies might be harnessed to develop a future generation of early cancer diagnostics...
  34. pmc Phylogenetic fate mapping
    Stephen J Salipante
    Department of Genome Sciences, Division of Medical Genetics, University of Washington School of Medicine, Box 357720, Seattle, WA 98195, USA
    Proc Natl Acad Sci U S A 103:5448-53. 2006
    ..The result is consistent with the present understanding of embryogenesis and demonstrates the large scale potential of this method for producing a complete mammalian cell fate at the resolution of a single cell...
  35. doi request reprint Neutropenia in 6 ethnic groups from the Caribbean and the U.S
    Victor R Grann
    Department of Medicine, College of Physicians and Surgeons, Columbia University, New York City, New York 10032, USA
    Cancer 113:854-60. 2008
    ....
  36. pmc Targets of the transcriptional repressor oncoprotein Gfi-1
    Zhijun Duan
    Division of Medical Genetics, Department of Medicine, University of Washington School of Medicine, 1705 Northeast Pacific Street, HSB K236B, P O Box 357720, Seattle, WA 98195, USA
    Proc Natl Acad Sci U S A 100:5932-7. 2003
    ....
  37. pmc Paradoxical homozygous expression from heterozygotes and heterozygous expression from homozygotes as a consequence of transcriptional infidelity through a polyadenine tract in the AP3B1 gene responsible for canine cyclic neutropenia
    Kathleen F Benson
    Division of Medical Genetics Department of Medicine, University of Washington School of Medicine, Box 357720, 1705 NE Pacific Street, HSB K236B, Seattle, WA 98195, USA
    Nucleic Acids Res 32:6327-33. 2004
    ..Out of frame transcripts are degraded, accounting for this paradox through the preferential accumulation of normal message from mutant alleles...
  38. ncbi request reprint Familial leukemia
    Kathleen F Benson
    Division of Medical Genetics, Department of Medicine, University of Washington School of Medicine, Box 357720, Seattle, WA 98195, USA
    Best Pract Res Clin Haematol 19:269-79. 2006
    ....
  39. doi request reprint Lymphadenopathy as the primary manifestation of malignant transformation in two patients with severe congenital neutropenia
    Christopher J Gamper
    Division of Pediatric Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Pediatr Blood Cancer 50:1072-5. 2008
    ....
  40. ncbi request reprint IKK gamma (NEMO) is involved in the coordination of the AP-1 and NF-kappa B pathways
    Amde Selassie Shifera
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, Forchheimer Bldg, Room 713, 1300 Morris Park Av, Bronx, NY 10461, USA
    Mol Cell Biochem 310:181-90. 2008
    ..Our results indicate that IKK gamma regulates TNF alpha signaling by coordinating cell responses mediated by the AP-1 and NF-kappa B pathways...
  41. ncbi request reprint The clinical, immunohematological, and molecular study of Iranian patients with severe congenital neutropenia
    Nima Rezaei
    Immunology, Asthma and Allergy Research Institute, Department of Allergy and Clinical Immunology of Children Medical Center, Medical Sciences University of Tehran, Tehran 14194, Iran
    J Clin Immunol 27:525-33. 2007
    ..Three patients died because of a severe infection. Although SCN is a rare disorder, early onset of severe and recurrent infections should always raise a suspicion, which deserves further evaluation for detecting such disorder...
  42. ncbi request reprint Function of adenovirus E3 proteins and their interactions with immunoregulatory cell proteins
    Marshall S Horwitz
    Albert Einstein College of Medicine, Department of Microbiology and Immunology, 1300 Morris Park Avenue, Bronx, NY 10461, USA
    J Gene Med 6:S172-83. 2004
    ..The use of Ad E3 immunoregulatory genes to facilitate allogeneic transplantation and prevent autoimmune diabetes will be described...

Research Grants21

  1. Genomic Fate Maps
    Marshall S Horwitz; Fiscal Year: 2010
    ..We will initially focus our studies on how the liver develops and responds to injury. ..
  2. Molecular Genetic Basic of Cyclic Hematopiesis
    Marshall S Horwitz; Fiscal Year: 2010
    ..3. Evaluate the genes encoding nodal points of the proposed feedback circuit as candidates for unaccounted cases of neutropenia. ..
  3. Mistargeting of Elastase in Bone Marrow Failure
    Marshall Horwitz; Fiscal Year: 2007
    ..1 Determine if ELA2 promoter variation contributes to neutropenia; 3.2 Measure the frequency of the ELA2 C-199A allele in individuals of African descent with benign ethnic neutropenia; 3.3 Identify new neutropenia genes. ..
  4. Molecular Genetic Basic of Cyclic Hematopiesis
    Marshall Horwitz; Fiscal Year: 2007
    ..3. Evaluate the genes encoding nodal points of the proposed feedback circuit as candidates for unaccounted cases of neutropenia. ..
  5. MEDICAL GENETICS POSTDOCTORAL FELLOWSHIP
    Marshall Horwitz; Fiscal Year: 2007
    ..As they progress, trainees are encouraged to seek individual fellowship awards. The Program continues in its successful mission of launching independent, research-focused careers in medical genetics. ..
  6. MOLECULAR GENETIC BASIS OF CYCLIC HEMATOPOIESIS
    Marshall Horwitz; Fiscal Year: 2006
    ..The broad, long-term objective is to understand the 21 day biological clock of the bone marrow, whose cycle is made evident in this disease. ..
  7. Genomic Fate Maps
    Marshall S Horwitz; Fiscal Year: 2010
    ..We will initially focus our studies on how the liver develops and responds to injury. ..