EDWARD HOWARD SCHUCHMAN

Summary

Affiliation: Mount Sinai School of Medicine
Country: USA

Publications

  1. pmc Acid sphingomyelinase promotes lipoprotein retention within early atheromata and accelerates lesion progression
    Cecilia M Devlin
    Department of Medicine, Columbia University, New York, NY 10032, USA
    Arterioscler Thromb Vasc Biol 28:1723-30. 2008
  2. pmc Acid ceramidase maintains the chondrogenic phenotype of expanded primary chondrocytes and improves the chondrogenic differentiation of bone marrow-derived mesenchymal stem cells
    Calogera M Simonaro
    Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York, United States of America
    PLoS ONE 8:e62715. 2013
  3. pmc Recombinant human acid sphingomyelinase as an adjuvant to sorafenib treatment of experimental liver cancer
    Radoslav Savic
    Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America
    PLoS ONE 8:e65620. 2013
  4. doi request reprint The genetics of sphingolipid hydrolases and sphingolipid storage diseases
    Edward H Schuchman
    Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY, 10029, USA
    Handb Exp Pharmacol 215:3-32. 2013
  5. doi request reprint Acid sphingomyelinase, cell membranes and human disease: lessons from Niemann-Pick disease
    Edward H Schuchman
    Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, Icahn Medical Institute, New York, NY 10029, USA
    FEBS Lett 584:1895-900. 2010
  6. ncbi request reprint The pathogenesis and treatment of acid sphingomyelinase-deficient Niemann-Pick disease
    E H Schuchman
    Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, 1425 Madison Avenue, Room 14 20A, New York, NY 10029, USA
    J Inherit Metab Dis 30:654-63. 2007
  7. ncbi request reprint The pathogenesis and treatment of acid sphingomyelinase-deficient Niemann-Pick disease
    E H Schuchman
    Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY 10029, USA
    Int J Clin Pharmacol Ther 47:S48-57. 2009
  8. ncbi request reprint Articular chondrocytes from animals with a dermatan sulfate storage disease undergo a high rate of apoptosis and release nitric oxide and inflammatory cytokines: a possible mechanism underlying degenerative joint disease in the mucopolysaccharidoses
    C M Simonaro
    Department of Human Genetics, Mount Sinai School of Medicine, New York, New York 10029, USA
    Lab Invest 81:1319-28. 2001
  9. ncbi request reprint Hematopoietic stem cell gene therapy for Niemann-Pick disease and other lysosomal storage diseases
    E H Schuchman
    Department of Human Genetics and Institute for Gene Therapy and Molecular Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA
    Chem Phys Lipids 102:179-88. 1999
  10. ncbi request reprint Gene therapy for genetic diseases
    R J Desnick
    Department of Human Genetics, Mount Sinai School of Medicine, New York, New York 10029, USA
    Acta Paediatr Jpn 40:191-203. 1998

Research Grants

  1. ACID CERAMIDASE, CERAMIDE & FARBER DISEASE
    EDWARD HOWARD SCHUCHMAN; Fiscal Year: 2010
  2. ACID SPHINGOMYELINASE AND NIEMANN-PICK DISEASE
    EDWARD SCHUCHMAN; Fiscal Year: 2006
  3. ACID SPHINGOMYELINASE & NIEMANN-PICK DISEASE
    EDWARD SCHUCHMAN; Fiscal Year: 2009
  4. ACID CERAMIDASE, CERAMIDE & FARBER DISEASE
    EDWARD SCHUCHMAN; Fiscal Year: 2009
  5. ACID CERAMIDASE, CERAMIDE & FARBER DISEASE
    EDWARD SCHUCHMAN; Fiscal Year: 2007
  6. ACID CERAMIDASE, CERAMIDE & FARBER DISEASE
    EDWARD SCHUCHMAN; Fiscal Year: 2006
  7. ACID SPHINGOMYELINASE & NIEMANN-PICK DISEASE
    EDWARD SCHUCHMAN; Fiscal Year: 2007
  8. ACID SPHINGOMYELINASE & NIEMANN-PICK DISEASE
    EDWARD SCHUCHMAN; Fiscal Year: 2009
  9. ACID SPHINGOMYELINASE AND NIEMANN-PICK DISEASE
    EDWARD SCHUCHMAN; Fiscal Year: 2005
  10. ACID SPHINGOMYELINASE AND NIEMANN-PICK DISEASE
    EDWARD SCHUCHMAN; Fiscal Year: 2004

Collaborators

Detail Information

Publications75

  1. pmc Acid sphingomyelinase promotes lipoprotein retention within early atheromata and accelerates lesion progression
    Cecilia M Devlin
    Department of Medicine, Columbia University, New York, NY 10032, USA
    Arterioscler Thromb Vasc Biol 28:1723-30. 2008
    ..We now sought to test a direct causative role for acid SMase in lipoprotein retention and atherogenesis in vivo...
  2. pmc Acid ceramidase maintains the chondrogenic phenotype of expanded primary chondrocytes and improves the chondrogenic differentiation of bone marrow-derived mesenchymal stem cells
    Calogera M Simonaro
    Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York, United States of America
    PLoS ONE 8:e62715. 2013
    ..The results also suggest that short-term changes in sphingolipid metabolism may lead to longer-term effects on the chondrogenic phenotype...
  3. pmc Recombinant human acid sphingomyelinase as an adjuvant to sorafenib treatment of experimental liver cancer
    Radoslav Savic
    Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America
    PLoS ONE 8:e65620. 2013
    ..Due to the hepatotropic nature of rhASM and its ability to generate pro-apoptotic ceramide, this study evaluated the use of rhASM as an adjuvant treatment with sorafenib in experimental models of HCC...
  4. doi request reprint The genetics of sphingolipid hydrolases and sphingolipid storage diseases
    Edward H Schuchman
    Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY, 10029, USA
    Handb Exp Pharmacol 215:3-32. 2013
    ..This review focuses on the genetics of sphingolipid storage diseases and related hydrolytic enzymes with an emphasis on the relationship between genetic mutations and human disease...
  5. doi request reprint Acid sphingomyelinase, cell membranes and human disease: lessons from Niemann-Pick disease
    Edward H Schuchman
    Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, Icahn Medical Institute, New York, NY 10029, USA
    FEBS Lett 584:1895-900. 2010
    ..This review will focus on the role of ASM in membrane biology, with a specific emphasis on what a rare genetic disorder (NPD) has taught us about more common events...
  6. ncbi request reprint The pathogenesis and treatment of acid sphingomyelinase-deficient Niemann-Pick disease
    E H Schuchman
    Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, 1425 Madison Avenue, Room 14 20A, New York, NY 10029, USA
    J Inherit Metab Dis 30:654-63. 2007
    ..Based on these studies in the mouse model, an enzyme replacement therapy clinical trial has recently begun in adult patients with non-neurological ASM-deficient NPD...
  7. ncbi request reprint The pathogenesis and treatment of acid sphingomyelinase-deficient Niemann-Pick disease
    E H Schuchman
    Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY 10029, USA
    Int J Clin Pharmacol Ther 47:S48-57. 2009
    ..Based on these studies, clinical trials of ERT are underway in patients with non-neurological ASM-deficient NPD...
  8. ncbi request reprint Articular chondrocytes from animals with a dermatan sulfate storage disease undergo a high rate of apoptosis and release nitric oxide and inflammatory cytokines: a possible mechanism underlying degenerative joint disease in the mucopolysaccharidoses
    C M Simonaro
    Department of Human Genetics, Mount Sinai School of Medicine, New York, New York 10029, USA
    Lab Invest 81:1319-28. 2001
    ..In turn, this leads to abnormal cartilage matrix homeostasis in the MPS individuals, which further exacerbates the joint deformities characteristic of these disorders...
  9. ncbi request reprint Hematopoietic stem cell gene therapy for Niemann-Pick disease and other lysosomal storage diseases
    E H Schuchman
    Department of Human Genetics and Institute for Gene Therapy and Molecular Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA
    Chem Phys Lipids 102:179-88. 1999
    ....
  10. ncbi request reprint Gene therapy for genetic diseases
    R J Desnick
    Department of Human Genetics, Mount Sinai School of Medicine, New York, New York 10029, USA
    Acta Paediatr Jpn 40:191-203. 1998
    ..Each of these gene delivery systems is reviewed here and their advantages and disadvantages compared. In addition, the current status and future prospects for human gene therapy trials for genetic diseases are discussed...
  11. ncbi request reprint Biochemical, pathological, and clinical response to transplantation of normal bone marrow cells into acid sphingomyelinase-deficient mice
    S R Miranda
    Department of Human Genetics and Brookdale Center for Molecular Biology, Mount Sinai School of Medicine, New York, New York 10029, USA
    Transplantation 65:884-92. 1998
    ..In the present study, we evaluated whether bone marrow transplantation (BMT) carried out on newborn ASMKO mice could prevent or alter the Niemann-Pick disease phenotype...
  12. ncbi request reprint Acid sphingomyelinase deficient mice: a model of types A and B Niemann-Pick disease
    K Horinouchi
    Department of Human Genetics, Mount Sinai School of Medicine, New York, New York 10029, USA
    Nat Genet 10:288-93. 1995
    ..Thus, the ASM deficient mice should be of great value for studying the pathogenesis and treatment of NPD, and for investigations into the role of ASM in signal transduction and apoptosis...
  13. pmc Niemann-Pick type B disease. Identification of a single codon deletion in the acid sphingomyelinase gene and genotype/phenotype correlations in type A and B patients
    O Levran
    Division of Medical and Molecular Genetics, Mount Sinai School of Medicine, New York, New York 10029
    J Clin Invest 88:806-10. 1991
    ..Although only two patients have been studied, it appears that the delta R608 mutation occurs frequently in Type B Niemann-Pick disease patients of Ashkenazi Jewish descent...
  14. ncbi request reprint Analysis of the lung pathology and alveolar macrophage function in the acid sphingomyelinase--deficient mouse model of Niemann-Pick disease
    R Dhami
    Department of Human Genetics, Mount Sinai School of Medicine, New York, New York 10029, USA
    Lab Invest 81:987-99. 2001
    ....
  15. ncbi request reprint Mucopolysaccharidosis type VI in rats: isolation of cDNAs encoding arylsulfatase B, chromosomal localization of the gene, and identification of the mutation
    T Kunieda
    Department of Human Genetics, Mount Sinai School of Medicine, New York, New York, USA
    Genomics 29:582-7. 1995
    ..Thus, we conclude that 507insC is the causative mutation in these animals and that the MPS VI rats are an authentic model of human MPS VI...
  16. ncbi request reprint Zn2+-stimulated sphingomyelinase is secreted by many cell types and is a product of the acid sphingomyelinase gene
    S L Schissel
    Department of Anatomy, Columbia University, New York, New York 10032, USA
    J Biol Chem 271:18431-6. 1996
    ..This secreted enzyme may play roles in physiological and pathophysiological processes involving extracellular sphingomyelin hydrolysis...
  17. ncbi request reprint Preimplantation diagnosis of a lysosomal storage disorder by in situ enzymatic activity: 'proof of principle' in acid sphingomyelinase-deficient mice
    A Butler
    Department of Human Genetics, Mount Sinai School of Medicine, 1425 Madision Avenue, New York, NY 10029, USA
    J Inherit Metab Dis 28:1-12. 2005
    ..We suggest that PED may be useful for the preimplantation diagnosis of lysosomal storage disorders, and perhaps other enzymatic defects where similar in situ assay methods are available...
  18. ncbi request reprint Identification of a missense mutation (S436R) in the acid sphingomyelinase gene from a Japanese patient with type B Niemann-Pick disease
    T Takahashi
    Mount Sinai School of Medicine, New York, New York 10029
    Hum Mutat 1:70-1. 1992
  19. ncbi request reprint An enzymatic assay for quantifying sphingomyelin in tissues and plasma from humans and mice with Niemann-Pick disease
    X He
    Department of Human Genetics, Mount Sinai School of Medicine, New York, New York 10029, USA
    Anal Biochem 293:204-11. 2001
    ....
  20. ncbi request reprint Identification and expression of a common missense mutation (L302P) in the acid sphingomyelinase gene of Ashkenazi Jewish type A Niemann-Pick disease patients
    O Levran
    Division of Medical and Molecular Genetics, Mount Sinai School of Medicine, New York, NY 10029
    Blood 80:2081-7. 1992
    ....
  21. ncbi request reprint Identification and expression of five mutations in the human acid sphingomyelinase gene causing types A and B Niemann-Pick disease. Molecular evidence for genetic heterogeneity in the neuronopathic and non-neuronopathic forms
    T Takahashi
    Division of Medical and Molecular Genetics, Mount Sinai School of Medicine, New York, New York 10029
    J Biol Chem 267:12552-8. 1992
    ..These findings have facilitated genotype/phenotype correlations for this lysosomal storage disease and provided insights into the functional organization of the ASM polypeptide...
  22. pmc Niemann-Pick disease: a frequent missense mutation in the acid sphingomyelinase gene of Ashkenazi Jewish type A and B patients
    O Levran
    Division of Medical and Molecular Genetics, Mount Sinai School of Medicine, New York, NY 10029
    Proc Natl Acad Sci U S A 88:3748-52. 1991
    ..The identification of this ASM mutation in Ashkenazi Jewish patients should facilitate the prevention of NPD in this population by carrier detection with molecular diagnostic techniques...
  23. ncbi request reprint Two new mutations in the acid sphingomyelinase gene causing type a Niemann-pick disease: N389T and R441X
    E H Schuchman
    Department of Human Genetics, Mount Sinai School of Medicine, New York, New York 10029, USA
    Hum Mutat 6:352-4. 1995
  24. ncbi request reprint N-acetylgalactosamine-4-sulfatase: identification of four new mutations within the conserved sulfatase region causing mucopolysaccharidosis type VI
    C M Simonaro
    Department of Human Genetics, Mount Sinai School of Medicine, New York, NY 10029, USA
    Biochim Biophys Acta 1272:129-32. 1995
    ..In fact, three of the mutations occurred within the same codon, W146. Thus, these results provide new insights into the molecular lesions causing MPS VI and highlight the importance of this conserved sulfatase region...
  25. ncbi request reprint Mouse models of Niemann-Pick disease: mutation analysis and chromosomal mapping rule out the type A and B forms
    K Horinouchi
    Department of Human Genetics, Mount Sinai School of Medicine, New York, NY 10029
    Genomics 18:450-1. 1993
  26. pmc Mucopolysaccharidosis type VI: identification of three mutations in the arylsulfatase B gene of patients with the severe and mild phenotypes provides molecular evidence for genetic heterogeneity
    W D Jin
    Division of Medical and Molecular Genetics, Mount Sinai School of Medicine, New York, NY 10029
    Am J Hum Genet 50:795-800. 1992
    ..The identification of these three ASB mutations documents the first evidence of molecular heterogeneity in MPS VI and provides an initial basis for genotype/phenotype correlations in this lysosomal storage disease...
  27. ncbi request reprint Structural organization and complete nucleotide sequence of the gene encoding human acid sphingomyelinase (SMPD1)
    E H Schuchman
    Division of Medical and Molecular Genetics, Mount Sinai School of Medicine, New York, New York 10029
    Genomics 12:197-205. 1992
    ..A single Alu1 element in the reverse orientation was in intron 2, immediately downstream from the type 2-specific sequence.(ABSTRACT TRUNCATED AT 250 WORDS)..
  28. ncbi request reprint Human acid sphingomyelinase. Isolation, nucleotide sequence and expression of the full-length and alternatively spliced cDNAs
    E H Schuchman
    Division of Medical and Molecular Genetics, Mount Sinai School of Medicine, New York, New York 10029
    J Biol Chem 266:8531-9. 1991
    ..The type 3 cDNA resulted from an alternative splicing event, which excised the 172-bp exon. These studies demonstrate the occurrence of alternatively splicing of the ASM transcript, but the existence of only one functional mRNA...
  29. pmc An MspI polymorphism in the human acid sphingomyelinase gene (SMPD1)
    E H Schuchman
    Division of Medical and Molecular Genetics, Mount Sinai School of Medicine, New York, NY 10029
    Nucleic Acids Res 19:3160. 1991
  30. ncbi request reprint The human acid ceramidase gene (ASAH): structure, chromosomal location, mutation analysis, and expression
    C M Li
    Department of Human Genetics, Mount Sinai School of Medicine, New York 10029, USA
    Genomics 62:223-31. 1999
    ..Although the levels of protein expression for these mutant ACs were about equivalent to that of the controls, their enzymatic activity was markedly reduced, confirming their authenticity...
  31. ncbi request reprint Regional assignment of the human acid sphingomyelinase gene (SMPD1) by PCR analysis of somatic cell hybrids and in situ hybridization to 11p15.1----p15.4
    L da Veiga Pereira
    Division of Medical and Molecular Genetics, Mount Sinai School of Medicine, New York, New York 10029
    Genomics 9:229-34. 1991
    ..In contrast to the previous provisional localization to chromosome 17, these results assign a single locus for human SMPD1 to 11p15.1----p15.4...
  32. ncbi request reprint Feline arylsulfatase B (ARSB): isolation and expression of the cDNA, comparison with human ARSB, and gene localization to feline chromosome A1
    C E Jackson
    Division of Medical and Molecular Genetics, Mount Sinai School of Medicine, New York, New York 10029
    Genomics 14:403-11. 1992
    ..The functional integrity of this cDNA was demonstrated by transient expression in human embryonic kidney cells.(ABSTRACT TRUNCATED AT 250 WORDS)..
  33. pmc Acid ceramidase improves the quality of oocytes and embryos and the outcome of in vitro fertilization
    Efrat Eliyahu
    Department of Genetics and Genomic Sciences, Mt Sinai School of Medicine, 1425 Madison Ave, Rm 14 20A, New York, NY 10029, USA
    FASEB J 24:1229-38. 2010
    ..Eliyahu, E., Shtraizent, N., Martinuzzi, K., Barritt, J., He, X., Wei, H., Chaubal, S., Copperman, A. B., Schuchman, E. H. Acid ceramidase improves the quality of oocytes and embryos and the outcome of in vitro fertilization...
  34. pmc Imprinting at the SMPD1 locus: implications for acid sphingomyelinase-deficient Niemann-Pick disease
    Calogera M Simonaro
    Department of Human Genetics, Mount Sinai School of Medicine, New York, NY 10029, USA
    Am J Hum Genet 78:865-70. 2006
    ..These data thus demonstrate, for the first time, imprinting at the SMPD1 gene and reveal the influence of this epigenetic modification on the presentation of ASM-deficient NPD...
  35. pmc Gene transfer of human acid sphingomyelinase corrects neuropathology and motor deficits in a mouse model of Niemann-Pick type A disease
    James C Dodge
    Genzyme Corporation, One Mountain Road, Framingham, MA 01701, USA
    Proc Natl Acad Sci U S A 102:17822-7. 2005
    ..Our results support the continued development of AAV based vectors for gene therapy of the CNS manifestations in Niemann-Pick type A disease...
  36. ncbi request reprint Identification of novel biomarkers for Niemann-Pick disease using gene expression analysis of acid sphingomyelinase knockout mice
    Rajwinder Dhami
    Department of Human Genetics, Mount Sinai School of Medicine, 1425 Madison Avenue, New York, NY 10029, USA
    Mol Ther 13:556-64. 2006
    ..These studies illustrate the value of gene expression analysis for the identification of biomarkers, and provide new insight into the pathobiology of NPD...
  37. ncbi request reprint Lysosomal enzyme delivery by ICAM-1-targeted nanocarriers bypassing glycosylation- and clathrin-dependent endocytosis
    Silvia Muro
    Institute for Environmental Medicine, University of Pennsylvania Medical School, 1 John Morgan Building, 3620 Hamilton Walk, Philadelphia, PA 19104 6068, USA
    Mol Ther 13:135-41. 2006
    ..Therefore, lysosomal enzyme targeting using nanocarriers targeted to ICAM-1 bypasses defunct pathways and may improve the efficacy of enzyme replacement therapy for lysosomal disorders, such as Niemann-Pick disease...
  38. ncbi request reprint A lipid analogue that inhibits sphingomyelin hydrolysis and synthesis, increases ceramide, and leads to cell death
    Peter I Darroch
    Department of Human Genetics, Mount Sinai School of Medicine, New York, NY 10029, USA
    J Lipid Res 46:2315-24. 2005
    ..Thus, AD2765 might be used to manipulate sphingomyelin metabolism in various ways, potentially to reduce substrate accumulation in cells from types A and B Niemann-Pick disease patients, and/or to affect the growth of human cancer cells...
  39. pmc Bone marrow transplantation for feline mucopolysaccharidosis I
    N Matthew Ellinwood
    Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Mol Genet Metab 91:239-50. 2007
    ..Immunohistochemical and biochemical analysis documented decreased central nervous system ganglioside storage. This large animal MPS I study will serve as a benchmark of future therapies designed to improve on BMT...
  40. pmc Combination brain and systemic injections of AAV provide maximal functional and survival benefits in the Niemann-Pick mouse
    Marco A Passini
    Genzyme Corporation, Framingham, MA 01701, USA
    Proc Natl Acad Sci U S A 104:9505-10. 2007
    ..These data demonstrate that combination therapy is a promising therapeutic modality for treating NPD and suggest a potential strategy for treating disease indications that cause both visceral and CNS pathologies...
  41. pmc Sperm abnormalities in heterozygous acid sphingomyelinase knockout mice reveal a novel approach for the prevention of genetic diseases
    Avigdor Butler
    Department of Human Genetics, Mount Sinai School of Medicine, 1425 Madison Avenue, Room 14 20A, New York, NY 10029, USA
    Am J Pathol 170:2077-88. 2007
    ..It therefore could have a major impact on the prevention of this and perhaps other genetic diseases...
  42. ncbi request reprint Intraparenchymal injections of acid sphingomyelinase results in regional correction of lysosomal storage pathology in the Niemann-Pick A mouse
    Wendy W Yang
    Genzyme Corporation, One Mountain Road, Framingham, MA 01701 9322, USA
    Exp Neurol 207:258-66. 2007
    ..These results indicate that intraparenchymal injection of hASM is associated with minimal toxicity and can lead to regional reductions in storage pathology in the ASMKO mouse...
  43. ncbi request reprint The sphingosine 1-phosphate receptor 1 causes tissue retention by inhibiting the entry of peripheral tissue T lymphocytes into afferent lymphatics
    Levi G Ledgerwood
    Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA
    Nat Immunol 9:42-53. 2008
    ..Thus, the increased sphingosine 1-phosphate present in inflamed peripheral tissues may induce T cell retention and suppress T cell egress...
  44. pmc Mechanism of glycosaminoglycan-mediated bone and joint disease: implications for the mucopolysaccharidoses and other connective tissue diseases
    Calogera M Simonaro
    Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, 1425 Madison Ave, New York, NY, 10029, USA
    Am J Pathol 172:112-22. 2008
    ..These findings have important implications for the pathogenesis and treatment of MPS and have further defined the mechanism of GAG-stimulated disease...
  45. doi request reprint Delivery of acid sphingomyelinase in normal and niemann-pick disease mice using intercellular adhesion molecule-1-targeted polymer nanocarriers
    Carmen Garnacho
    Department of Pharmacology, John Morgan Bldg, 3620 Hamilton Walk, Philadelphia, PA 19104 6068, USA
    J Pharmacol Exp Ther 325:400-8. 2008
    ..These data demonstrate that ICAM-1-targeted nanocarriers may enhance enzyme replacement therapy for type B NPD and perhaps other lysosomal storage disorders...
  46. pmc The unexpected role of acid sphingomyelinase in cell death and the pathophysiology of common diseases
    Eric L Smith
    Department of Genetics and Genomic Sciences, Mt Sinai School of Medicine, 1425 Madison Ave, New York, NY 10029, USA
    FASEB J 22:3419-31. 2008
    ....
  47. ncbi request reprint AAV8-mediated hepatic expression of acid sphingomyelinase corrects the metabolic defect in the visceral organs of a mouse model of Niemann-Pick disease
    Christine M Barbon
    Genzyme Corporation, 31 New York Avenue, Framingham, MA 01701 9322, USA
    Mol Ther 12:431-40. 2005
    ..Together, these data support the continued development of AAV8-mediated hepatic gene transfer as an approach to treat the visceral manifestations observed in individuals with acid sphingomyelinase deficiency...
  48. ncbi request reprint Growth restriction in children with type B Niemann-Pick disease
    Melissa P Wasserstein
    Department of Human Genetics, and the Carl C Icahn Institute for Gene Therapy and Molecular Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA
    J Pediatr 142:424-8. 2003
    ..To compare growth of children with type B Niemann-Pick disease (NPD) with disease variables including genotype, organomegaly, bone age, and serum insulin-like growth factor-1 (IGF-1)...
  49. ncbi request reprint The reverse activity of human acid ceramidase
    Nozomu Okino
    Department of Human Genetics, Mount Sinai School of Medicine, New York, New York 10029, USA
    J Biol Chem 278:29948-53. 2003
    ..These data provide important new information on human acid ceramidase and further document its central role in sphingolipid metabolism...
  50. ncbi request reprint Purification and characterization of recombinant, human acid ceramidase. Catalytic reactions and interactions with acid sphingomyelinase
    Xingxuan He
    Department of Human Genetics, Mount Sinai School of Medicine, New York, New York 10029, USA
    J Biol Chem 278:32978-86. 2003
    ..These studies provide new insights into acid ceramidase and the related lipid hydrolase, acid sphingomyelinase...
  51. ncbi request reprint Alveolar lipoproteinosis in an acid sphingomyelinase-deficient mouse model of Niemann-Pick disease
    Machiko Ikegami
    Cincinnati Children s Hospital Medical Center, Division of Pulmonary Biology, Cincinnati, Ohio 45229, USA
    Am J Physiol Lung Cell Mol Physiol 284:L518-25. 2003
    ..Alterations in surfactant composition, including increased sphingomyelin content, contributed to the abnormal surfactant function observed in the ASM-deficient mouse...
  52. ncbi request reprint Mannose 6-phosphate receptor-mediated uptake is defective in acid sphingomyelinase-deficient macrophages: implications for Niemann-Pick disease enzyme replacement therapy
    Rajwinder Dhami
    Department of Human Genetics, Mount Sinai School of Medicine, New York, New York 10029, USA
    J Biol Chem 279:1526-32. 2004
    ..These findings have important implications for NPD enzyme replacement therapy, particularly in the lung...
  53. ncbi request reprint Enzyme replacement and enhancement therapies: lessons from lysosomal disorders
    Robert J Desnick
    Department of Human Genetics, Mount Sinai School of Medicine at New York University, New York, New York 10029, USA
    Nat Rev Genet 3:954-66. 2002
    ..This review discusses the successes and shortcomings of these therapeutic strategies, and the contributions that they have made to treating lysosomal storage diseases...
  54. ncbi request reprint Ex vivo gene therapy using bone marrow-derived cells: combined effects of intracerebral and intravenous transplantation in a mouse model of Niemann-Pick disease
    Hee Kyung Jin
    Department of Human Genetics, Mount Sinai School of Medicine, New York, New York 10029, USA
    Mol Ther 8:876-85. 2003
    ....
  55. ncbi request reprint Ocular manifestations of Niemann-Pick disease type B
    Margaret M McGovern
    Department of Human Genetics and Pediatrics, Mount Sinai School of Medicine, New York, New York 10029, USA
    Ophthalmology 111:1424-7. 2004
    ..To investigate the ocular manifestations in Niemann-Pick disease type B (NPD-B)...
  56. ncbi request reprint Lipid abnormalities in children with types A and B Niemann Pick disease
    Margaret M McGovern
    Department of Human Genetics, Mount Sinai School of Medicine, New York, New York 10029, USA
    J Pediatr 145:77-81. 2004
    ..To characterize the lipid profiles in patients with types A and B Niemann Pick disease (NPD) and determine if lipid abnormalities are associated with evidence of early cardiovascular disease or correlate with genotype...
  57. pmc The demographics and distribution of type B Niemann-Pick disease: novel mutations lead to new genotype/phenotype correlations
    Calogera M Simonaro
    Department of Human Genetics, Mount Sinai School of Medicine, New York, NY 10029, USA
    Am J Hum Genet 71:1413-9. 2002
    ..These data provide the first extensive demographic assessment of this disorder and describe several new mutations that can be used to predict phenotypic outcome and to gain new insights into the structure and function of ASM...
  58. pmc Intracerebral transplantation of mesenchymal stem cells into acid sphingomyelinase-deficient mice delays the onset of neurological abnormalities and extends their life span
    Hee Kyung Jin
    Department of Human Genetics, Mount Sinai School of Medicine, New York, New York 1029, USA
    J Clin Invest 109:1183-91. 2002
    ..These results reveal the potential of treating neurodegenerative lysosomal storage disorders by intracerebral transplantation of bone marrow-derived MSCs...
  59. ncbi request reprint AAV vector-mediated correction of brain pathology in a mouse model of Niemann-Pick A disease
    Marco A Passini
    Neuroscience, Genzyme Corporation, One Mountain Road, Framingham, MA 01701, USA
    Mol Ther 11:754-62. 2005
    ..These findings show that the ASMKO brain is responsive to ASM replacement and that retrograde transport of AAV2 functions as a platform for widespread gene delivery and reversal of pathology in affected brain...
  60. ncbi request reprint A fluorescence-based, high-throughput sphingomyelin assay for the analysis of Niemann-Pick disease and other disorders of sphingomyelin metabolism
    Xingxuan He
    Department of Human Genetics, Mount Sinai School of Medicine, New York, New York 10029, USA
    Anal Biochem 306:115-23. 2002
    ..It could also be a useful tool for the study of other sphingomyelin-related diseases and in a variety of research settings where sphingomyelin quantification is required...
  61. ncbi request reprint Joint and bone disease in mucopolysaccharidoses VI and VII: identification of new therapeutic targets and biomarkers using animal models
    Calogera M Simonaro
    Department of Human Genetics, Mount Sainai School of Medicine, New York, NY 10029, USA
    Pediatr Res 57:701-7. 2005
    ..This information should aid in the evaluation of existing therapies for these disorders, such as enzyme replacement therapy and bone marrow transplantation, and may lead to the development of new therapeutic approaches...
  62. ncbi request reprint Preimplantation genetic diagnosis for Niemann-Pick disease type B
    Ali Hellani
    King Faisal Specialist Hospital and Research Center, PO Box 3354, MBC 10, Riyadh 11211, Saudi Arabia
    Prenat Diagn 24:943-8. 2004
    ..Given the difficult management of the disease, we opted for a preventive approach to the suffering families by screening the whole SMPD1 gene for mutations followed by Preimplantation Genetic Diagnosis (PGD)...
  63. ncbi request reprint The natural history of type B Niemann-Pick disease: results from a 10-year longitudinal study
    Melissa P Wasserstein
    Department of Human Genetics, Mount Sinai School of Medicine, New York, New York, USA
    Pediatrics 114:e672-7. 2004
    ..The objectives of this study were to document the natural history of the disease in a large, clinically heterogeneous patient population that was followed for a period of 10 years and to determine how genotype influences phenotype...
  64. pmc Reproductive pathology and sperm physiology in acid sphingomyelinase-deficient mice
    Avigdor Butler
    Department of Human Genetics, Mount Sinai School of Medicine, New York, New York 10029, USA
    Am J Pathol 161:1061-75. 2002
    ..These results provide in vivo evidence that ASM activity plays a critical role in sperm maturation and function, and a basis for similar studies in sexually mature, male NPD patients...
  65. ncbi request reprint Acid sphingomyelinase overexpression enhances the antineoplastic effects of irradiation in vitro and in vivo
    Eric L Smith
    Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York 10029, USA
    Mol Ther 16:1565-71. 2008
    ..Based on the data presented in this article, we propose that further investigation of this protein and gene as antineoplastic agents also is warranted...
  66. ncbi request reprint Neurodegeneration augments the ability of bone marrow-derived mesenchymal stem cells to fuse with Purkinje neurons in Niemann-Pick type C mice
    Jae Sung Bae
    College of Veterinary Medicine, Kyungpook National University, Daegu, South Korea
    Hum Gene Ther 16:1006-11. 2005
    ..The results suggest that the degenerative microenvironment of Purkinje neurons in the NP-C cerebellum modulates the cell fate switch of BM-MSCs via cell fusion...
  67. ncbi request reprint A fluorescence-based, high-performance liquid chromatographic assay to determine acid sphingomyelinase activity and diagnose types A and B Niemann-Pick disease
    Xingxuan He
    Department of Human Genetics, Mount Sinai School of Medicine, New York, NY 10029, USA
    Anal Biochem 314:116-20. 2003
    ....
  68. pmc Autoproteolytic cleavage and activation of human acid ceramidase
    Nataly Shtraizent
    Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York 10029, USA
    J Biol Chem 283:11253-9. 2008
    ..Treatment of recombinant AC with the cysteine protease inhibitor, methyl methanethiosulfonate, inhibited both cleavage and enzymatic activity, further indicating that cysteine-mediated self-cleavage is required for ceramide hydrolysis...
  69. ncbi request reprint Nitric oxide boosts chemoimmunotherapy via inhibition of acid sphingomyelinase in a mouse model of melanoma
    Cristiana Perrotta
    H San Raffaele Scientific Institute, Italy
    Cancer Res 67:7559-64. 2007
    ....
  70. ncbi request reprint Dexamethasone-mediated up-regulation of the mannose receptor improves the delivery of recombinant glucocerebrosidase to Gaucher macrophages
    Yunxiang Zhu
    Genzyme Corporation, Framingham, MA 01701 9322, USA
    J Pharmacol Exp Ther 308:705-11. 2004
    ..Together, these data suggest that pretreatment with dexamethasone could specifically enhance the presentation of mannose receptors on Gaucher macrophages with resultant improvement in delivery of the enzyme to the affected cells...
  71. ncbi request reprint Bone marrow-derived mesenchymal stem cells promote neuronal networks with functional synaptic transmission after transplantation into mice with neurodegeneration
    Jae Sung Bae
    Departments of Physiology, College of Medicine, Kyungpook National University, Korea
    Stem Cells 25:1307-16. 2007
    ..Disclosure of potential conflicts of interest is found at the end of this article...
  72. ncbi request reprint Acid ceramidase and human disease
    Jae Ho Park
    Department of Human Genetics, Mount Sinai School of Medicine, 1425 Madison Avenue, Room 14 20A, New York, NY 10029, USA
    Biochim Biophys Acta 1758:2133-8. 2006
    ..Current information concerning the biology of this enzyme and its role in human disease is reviewed within...
  73. ncbi request reprint Simultaneous quantitative analysis of ceramide and sphingosine in mouse blood by naphthalene-2,3-dicarboxyaldehyde derivatization after hydrolysis with ceramidase
    Xingxuan He
    Department of Human Genetics, Mount Sinai School of Medicine, New York, NY 10029, USA
    Anal Biochem 340:113-22. 2005
    ..In the future it could be an important tool for investigators studying the role of ceramide/sphingosine metabolism in signal transduction, cell growth and differentiation, and cancer pathogenesis and treatment...
  74. ncbi request reprint Acid sphingomyelinase: relation of 93lysine residue on the ratio of intracellular to secreted enzyme activity
    Ikuko Takahashi
    Department of Pediatrics, Akita University School of Medicine, 1 1 1 Hondo, Akita, Japan
    Tohoku J Exp Med 206:333-40. 2005
    ....
  75. ncbi request reprint Insertional mutagenesis of the mouse acid ceramidase gene leads to early embryonic lethality in homozygotes and progressive lipid storage disease in heterozygotes
    Chi Ming Li
    Department of Human Genetics, Mount Sinai School of Medicine, New York, New York 10029, USA
    Genomics 79:218-24. 2002
    ....

Research Grants24

  1. ACID CERAMIDASE, CERAMIDE & FARBER DISEASE
    EDWARD HOWARD SCHUCHMAN; Fiscal Year: 2010
    ..We will continue to characterize the inhibitory effects of novel sphingolipid analogues in vitro and in situ, and evaluate their use for chaperone therapy of Farber disease. ..
  2. ACID SPHINGOMYELINASE AND NIEMANN-PICK DISEASE
    EDWARD SCHUCHMAN; Fiscal Year: 2006
    ..We believe that this research will provide fundamental insights into the underlying biology of NPD & ASM, and lead to the development of effective treatments for these disorders and/or methods to prevent or minimize NPD births. ..
  3. ACID SPHINGOMYELINASE & NIEMANN-PICK DISEASE
    EDWARD SCHUCHMAN; Fiscal Year: 2009
    ..These studies will also investigate the broader role of ASM in health & disease, in particular the relationship between ASM activity & pulmonary fibrosis. ..
  4. ACID CERAMIDASE, CERAMIDE & FARBER DISEASE
    EDWARD SCHUCHMAN; Fiscal Year: 2009
    ..We will continue to characterize the inhibitory effects of novel sphingolipid analogues in vitro and in situ, and evaluate their use for chaperone therapy of Farber disease. ..
  5. ACID CERAMIDASE, CERAMIDE & FARBER DISEASE
    EDWARD SCHUCHMAN; Fiscal Year: 2007
    ..We will continue to characterize the inhibitory effects of novel sphingolipid analogues in vitro and in situ, and evaluate their use for chaperone therapy of Farber disease. ..
  6. ACID CERAMIDASE, CERAMIDE & FARBER DISEASE
    EDWARD SCHUCHMAN; Fiscal Year: 2006
    ..We will continue to characterize the inhibitory effects of novel sphingolipid analogues in vitro and in situ, and evaluate their use for chaperone therapy of Farber disease. ..
  7. ACID SPHINGOMYELINASE & NIEMANN-PICK DISEASE
    EDWARD SCHUCHMAN; Fiscal Year: 2007
    ..These studies will also investigate the broader role of ASM in health & disease, in particular the relationship between ASM activity & pulmonary fibrosis. ..
  8. ACID SPHINGOMYELINASE & NIEMANN-PICK DISEASE
    EDWARD SCHUCHMAN; Fiscal Year: 2009
    ..These studies will also investigate the broader role of ASM in health & disease, in particular the relationship between ASM activity & pulmonary fibrosis. ..
  9. ACID SPHINGOMYELINASE AND NIEMANN-PICK DISEASE
    EDWARD SCHUCHMAN; Fiscal Year: 2005
    ..We believe that this research will provide fundamental insights into the underlying biology of NPD & ASM, and lead to the development of effective treatments for these disorders and/or methods to prevent or minimize NPD births. ..
  10. ACID SPHINGOMYELINASE AND NIEMANN-PICK DISEASE
    EDWARD SCHUCHMAN; Fiscal Year: 2004
    ..We believe that this research will provide fundamental insights into the underlying biology of NPD & ASM, and lead to the development of effective treatments for these disorders and/or methods to prevent or minimize NPD births. ..
  11. CERAMIDASES, CERAMIDE, AND FARBER DISEASE
    EDWARD SCHUCHMAN; Fiscal Year: 2004
    ..abstract_text> ..
  12. CERAMIDASES, CERAMIDE, AND FARBER DISEASE
    EDWARD SCHUCHMAN; Fiscal Year: 2001
    ..abstract_text> ..
  13. ACID SPHINGOMYELINASE AND NIEMANN-PICK DISEASE
    EDWARD SCHUCHMAN; Fiscal Year: 2001
    ..These animal model studies are expected to provide fundamental information on the pathophysiology of NPD and the role of ASM in mammalian development and disease pathogenesis. ..
  14. CERAMIDASES, CERAMIDE, AND FARBER DISEASE
    EDWARD SCHUCHMAN; Fiscal Year: 2002
    ..abstract_text> ..
  15. ACID SPHINGOMYELINASE AND NIEMANN-PICK DISEASE
    EDWARD SCHUCHMAN; Fiscal Year: 2003
    ..We believe that this research will provide fundamental insights into the underlying biology of NPD & ASM, and lead to the development of effective treatments for these disorders and/or methods to prevent or minimize NPD births. ..
  16. CERAMIDASES, CERAMIDE, AND FARBER DISEASE
    EDWARD SCHUCHMAN; Fiscal Year: 2003
    ..abstract_text> ..
  17. ACID SPHINGOMYELINASE AND NIEMANN-PICK DISEASE
    EDWARD SCHUCHMAN; Fiscal Year: 2002
    ..We believe that this research will provide fundamental insights into the underlying biology of NPD & ASM, and lead to the development of effective treatments for these disorders and/or methods to prevent or minimize NPD births. ..
  18. ACID SPHINGOMYELINASE AND NIEMANN-PICK DISEASE
    EDWARD SCHUCHMAN; Fiscal Year: 2000
    ..These animal model studies are expected to provide fundamental information on the pathophysiology of NPD and the role of ASM in mammalian development and disease pathogenesis. ..
  19. ACID SPHINGOMYELINASE AND NIEMANN-PICK DISEASE
    EDWARD SCHUCHMAN; Fiscal Year: 1999
    ..These animal model studies are expected to provide fundamental information on the pathophysiology of NPD and the role of ASM in mammalian development and disease pathogenesis. ..
  20. ACID SPHINGOMYELINASE & NIEMANN-PICK DISEASE
    EDWARD HOWARD SCHUCHMAN; Fiscal Year: 2010
    ..These studies will also investigate the broader role of ASM in health &disease, in particular the relationship between ASM activity &pulmonary fibrosis. ..