Our Scientific Advisors
Seng Cheng, PhD – Global Head of Research, Rare Diseases Division at Sanofi.
Dr. Cheng received his BSc, and PhD degrees in Biochemistry from the University of London, U.K. He trained as a postdoctoral fellow at the National Institute for Medical Research in London, U.K., in the field of tumor biology. He was a Staff Scientist at Integrated Genetics Inc., and later joined Genzyme Corporation to work on several discovery projects including the structure and function of the cystic fibrosis transmembrane conductance regulator. As Group Vice President of Genetic Diseases Science at Genzyme, he also managed the development of novel gene delivery vector systems as well as translational research of genetic diseases, a number of which transitioned to clinical testing. Areas of focus included inherited metabolic, muscle, lung and neurodegenerative diseases. He has published over 240 research articles and reviews, and is a named inventor on 45 issued patents in the area of biotechnology. In his current position, he is responsible for directing the translational research and early clinical development activities in rare genetic diseases.
Edward H. Schuchman, PH. D – Professor Genetics and Geomics Sciences at Mount Sinai, NY. Cancer Biology (CAB) and genetics and Genomic Sciences (GGS).
B.S., State University of New York at Stony Brook. Biochemistry. Ph.D., Mount Sinai School of Medicine Human Genetics. Postodoctoral, Yale University School of Medicine. Molecular Genetics.
Specific Clinical/Research Interest:
The biology and treatment of lysosomal storage disorders; the role of lipid hydrolases in cell signaling
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.
Maria Dolores (LOLA) Ledesma, PH.D – Center of Molecular Biology in Spain. Molecular Neuobiology Specialty.
Our laboratory is interested in understanding the role that lipids play in neuronal physiology and pathology with special emphasis on its participation in the synapse. In recent years much progress has been made in understanding the protein machinery that regulates synaptic transmission. However, much less is known about the contribution of lipid although essential synaptic activity is regulated by protein binding to the membranes , the lipids are major components . Also, dynamic membranes is the basis for the transmission of information . The fact that most lipidosis caused cognitive defects and mental retardation is also a reflection of the importance of the lipids in this process . Lipids are focused our studies sphingolipids and cholesterol because, among other reasons , they are particularly abundant in neurons , and are capable of forming signaling platforms . Mice were used as experimental models in which enzymes involved in the metabolism of these lipids are genetically altered and which allow in vivo analysis . The models that we are currently mice deficient in acid sphingomyelinase and the Seladin one responsible recycling of sphingomyelin and cholesterol synthesis , respectively. These mice mimic human genetic diseases such as Niemann Pick type A or desmosteroslosis that cause severe mental retardation. Furthermore, we have found lipid abnormalities in these mice ( Crameri et al , EMBO J , 2006,. . . . Galvan et al , Mol Biol Cell, 2008 ) are similar to those found in aged brains. This opens the possibility that our results have implications not only in the formation and maintenance of synapses but also in functional decline during aging. We hope therefore contribute to understanding neurological diseases of childhood and neurodegenerative as Alzheimer ‘s disease.
Dr. Melissa Wasserstein – Clinical Genetics MD, Clinical Biochemical Genetics
Medical Genetics, Pediatric Genetics, Inborn Errors of Metabolism, Lysosomal Storage Diseases, Newborn Screening, Urea Cycle Disorders, Hyperammonemia, Fatty Acid Oxidation Defects, Organic Acidemias, Maple Syrup Urine Disease
Dr. Wasserstein is the Director of the Program for Inherited Metabolic Diseases (PIMD) at Mount Sinai Medical Center. This program is one of the largest metabolic disease treatment programs in the country, treating several hundred patients who are diagnosed with rare inborn errors of metabolism. The PIMD is a New York State Newborn Screening designated referral center for infants with inherited metabolic diseases, and is also the leading referral center in the region for the evaluation of patients with suspected inborn errors of metabolism. Disorders that are treated at the PIMD include:
Dr. Wasserstein is part of Mount Sinai’s International Center for Types A and B Niemann-Pick disease. She is also a clinical researcher, focusing on evaluating the safety and effectiveness of novel treatments for patients with inborn errors of metabolism.