Research Topics
- Angiogenesis
- Apoptosis/Cell Death
- Blood-Brain Barrier
- Bone Metabolism
- Brain
- Cancer
- Cardiovascular
- Cartilage Biology
- Cellular Differentiation
- Chemokines
- Chemotaxis
- Cytokines
- Endothelial Cells
- Enzymology
- Fibrosis
- Gene Regulation
- Gene Therapy
- Genetics
- Genomics
- Human Genetics and Genetic Disorders
- Inflammation
- Lipid Signaling
- Lysosomal Storage Diseases
- Lysosomes/endosome
- Macrophage
- Mental Retardation
- Metastasis
- Neuro-degeneration/protection
- Protein Trafficking & Sorting
- Reproductive Biology
- Signal Transduction
- Stem Cells
- Tumorigenesis
Training Areas
Awards
2013 -
Inventor of the Year
New York Intellectual Property Law Association2012 -
Named Postdoctoral Fellowship
National Niemann-Pick Disease Foundation2008 -
Dean's Award for Translational Research
Ichan School of Medicine at Mount Sinai2007 -
Francis Crick Chair in Genetics and Genomic Sciences
Genetic Disease Foundation2003 -
Faculty Council Award for Academic Excellence
Ichan School of Medicine at Mount Sinai
Research
Specific Clinical/Research Interest:The biology and treatment of lysosomal storage disorders; the role of lipid hydrolases in cell signaling
Postdoctoral Fellows: Radoslav Savic, Michael Frobergh
Research Personnel:
Research Faculty: Xingxuan He, Research Assistant: Yi Ge, Fanli Meng, Changzhi Zhu
Summary of Research Studies:
Our laboratory studies the biology of lysosomal enzymes, genes and diseases. Two of the main projects in the lab are focused on the enzymes acid sphingomyelinase (deficient in Types A & B Niemann-Pick disease) and acid ceramidase (deficient in Farber Lipogranulomatosis or Farber disease). We integrate the tools of molecular biology, biochemistry, pharmacology and other disciplines to understand the pathogenic mechanisms causing these disorders and to develop new therapies. Our lab is responsible for the gene cloning of both enzymes, identification of the first mutations causing the human diseases, production and characterization of both human recombinant enzymes, and the construction of the first animal models for the human diseases. This work has led to the first enzyme replacement therapy clinical trials for Niemann-Pick disease (collaboration with the Genzyme/Sanofi), institution of the first genetic screening program for this disorder throughout the world, and the formation of a new company (Plexcera Therapeutics) to develop enzyme therapy for Farber disease. We continue to work closely on the role of acid sphingomyelinase and acid ceramidase in lipid-mediated cell signaling and to understand how these enzyme and genes are involved in various other disease pathologies, including common disorders such as type II diabetes and monogenic disorders such as cystic fibrosis. We also collaborate on the development of new therapies for another group of lysosomal storage disorders, the mucopolysaccharidoses.
Publications
Simonaro CM, D'Angelo M, He X, Schuchman EH, Shtraizent N, Haskins ME, Eliyahu E. Mechanism of glycosaminoglycan-mediated joint and bone disease: Implications for the mucopolysaccharodoses & other connective tissue diseases. Am. J. Path 2008; 172: 112-122.
Shtraizent N, Eliyahu E, Park J, He X, Shalgi R, Schuchman EH. Autoproteolytic cleavage and activation of human acid ceramidase. J. Biol. Chem 2008; 283: 11253-11259.
Smith EL, Schuchman EH. Acid sphingomyelinase enhances the anti-oncogenic effects of irradiation in vitro and in vivo. Mol. Ther 2008; 16: 1565-1571.
He X, Huang Y, Li B, Gong C, Schuchman H. Deregulation of sphingolipid metabolism in Alzheimer's disease [Epub ahead of print]. Neur. Biol. Ageing 2008;.
Jones I, He X, Darroch P, Schuchman EH. Characterization of common SMPD1 mutations causing types A and B Niemann-Pick disease and generation of mutation-specific mouse models. Mol. Gen. Met 2008; 95: 152-162.
Simonaro CM, Sachot S, Ge Y, He X, Deangelis VA, Eliyahu E, Leong DJ, Sun HB, Mason JB, Haskins ME, Richardson DW, Schuchman EH. Acid ceramidase maintains the chondrogenic phenotype of expanded primary chondrocytes and improves the chondrogenic differentiation of bone marrow-derived mesenchymal stem cells. PloS one 2013; 8(4).
Schuchman EH, Ge Y, Lai A, Borisov Y, Faillace M, Eliyahu E, He X, Iatridis J, Vlassara H, Striker G, Simonaro CM. Pentosan polysulfate: a novel therapy for the mucopolysaccharidoses. PloS one 2013; 8(1).
Simonaro CM, Ge Y, Eliyahu E, He X, Jepsen KJ, Schuchman EH. Involvement of the Toll-like receptor 4 pathway and use of TNF-alpha antagonists for treatment of the mucopolysaccharidoses. Proceedings of the National Academy of Sciences of the United States of America 2010 Jan; 107(1).
Savić R, He X, Fiel I, Schuchman EH. Recombinant human acid sphingomyelinase as an adjuvant to sorafenib treatment of experimental liver cancer. PloS one 2013; 8(5).
Dhami R, He X, Schuchman EH. Acid sphingomyelinase deficiency attenuates bleomycin-induced lung inflammation and fibrosis in mice. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 2010; 26(4-5).
Schuchman EH. Acid sphingomyelinase, cell membranes and human disease: lessons from Niemann-Pick disease. FEBS letters 2010 May; 584(9).
Eliyahu E, Shtraizent N, Martinuzzi K, Barritt J, He X, Wei H, Chaubal S, Copperman AB, Schuchman EH. Acid ceramidase improves the quality of oocytes and embryos and the outcome of in vitro fertilization. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2010 Apr; 24(4).
Industry Relationships
Physicians and scientists on the faculty of the Icahn School of Medicine at Mount Sinai often interact with pharmaceutical, device and biotechnology companies to improve patient care, develop new therapies and achieve scientific breakthroughs. In order to promote an ethical and transparent environment for conducting research, providing clinical care and teaching, Mount Sinai requires that salaried faculty inform the School of their relationships with such companies.
Below are financial relationships with industry reported by Dr. Schuchman during 2014 and/or 2015. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.
Consulting:
- Genzyme Corporation; Orphazyme
Service on Board of Directors: Service in a fiduciary capacity, such as an officer or director, for the following companies:
- Plexcera Therapeutics
Royalty Payments:
- Genzyme Corporation; Luminex Corporation
Equity (Stock or stock options valued at greater than 5% ownership of a publicly traded company or equity of any value in a privately held company)
- Plexcera Therapeutics
Mount Sinai's faculty policies relating to faculty collaboration with industry are posted on our website at http://icahn.mssm.edu/about-us/services-and-resources/faculty-resources/handbooks-and-policies/faculty-handbook. Patients may wish to ask their physician about the activities they perform for companies.
Icahn Medical Institute Floor 14 Room 14-26A (Lab)
1425 Madison Avenue
New York, NY 10029
Icahn Medical Institute Floor 14 Room 14-20A
1425 Madison Avenue
New York, NY 10029
Fax: 212-849-2447