Photo of Calogera Simonaro

Calogera Simonaro

  • RESEARCH PROFESSOR Genetics and Genomic Sciences
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Education

  • B.A., St. John's University

  • M.S., Brooklyn College

  • Ph.D., New York University

  • Mount Sinai School of Medicine

  • M.Ph., New York University

Research


Postdoctoral Fellows: Michael Frobergh

Research Personnel: Research Assistant: Yi Ge, Fanli Meng, Changzhi Zhu

 The overall goal of our research is to fill the void in our understanding of MPS bone and joint disease and to develop new and improved therapies that might benefit MPS patients. We specifically study two animal models with MPS VI, but anticipate that the results obtained can be applicable to the general class of MPS disorders and benefit a wide range of patients.

Our studies carried out over the past five years have revealed that glycosaminoglycan GAG accumulation is a direct cause of chondrocyte death (apoptosis) in the articular cartilage and growth plates of MPS animals, leading to abnormal matrix homeostasis. This enhanced cell death also triggers a series of signaling events that lead to marked inflammatory disease with characteristic increases in proinflammatory cytokines, metalloproteinases (MMPs), and apoptotic cells. Together, these two factors (enhanced cell death and inflammation), lead to the characteristic bone and joint disease in the MPS disorders. In addition, cellular defects associated with the maturation of MPS growth plates are likely contributing to abnormal bone growth.

Enzyme replacement studies in MPS animals and human patients have revealed that chondrocytes in joints and bones are difficult to reach following injection due to the poor vascular supply to these tissues and the fact that the target cells are embedded in a dense matrix. With the availability of enzyme replacement it is important to continue to investigate new approaches for improving enzyme delivery to these critical target tissues.

Our findings have important implications for the treatment of MPS individuals, as well as for the identification of novel biomarkers to monitor disease progression and therapeutic efficacy. In addition, many of the pathologic processes in the MPS bones and joints have close similarities to those that occur in arthritis. Thus, some of the important biomarkers and therapeutic targets for arthritis should be considered for MPS.

Publications

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, 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, Simonaro CM. The genetics of sphingolipid hydrolases and sphingolipid storage diseases. Handbook of experimental pharmacology 2013;(215).

Lai A, Simonaro CM, Schuchman EH, Ge Y, Laudier DM, Iatridis JC. Structural, compositional, and biomechanical alterations of the lumbar spine in rats with mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome). Journal of orthopaedic research : official publication of the Orthopaedic Research Society 2013 Apr; 3(4).

Eliyahu E, Wolfson T, Ge Y, Jepsen KJ, Schuchman EH, Simonaro CM. Anti-TNF-alpha therapy enhances the effects of enzyme replacement therapy in rats with mucopolysaccharidosis type VI. PloS one 2011; 6(8).

Simonaro CM. Cartilage and chondrocyte pathology in the mucopolysaccharidoses: The role of glycosaminoglycan-mediated inflammation. Journal of pediatric rehabilitation medicine 2010; 3(2).

Simonaro CM, D'Angelo M, He X, Shtraizent N, Haskins ME, Schuchman EH. Mechanism of Glycosaminoglycan-Mediated Bone & Joint Disease: Implications for the Mucopolysaccharidoses & Other Connective Tissue Diseases. Amer J Path 2008; 172(1): 112-122.

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. Simonaro during 2012 and/or 2013. Please note that this information may differ from information posted on corporate sites due to timing or classification differences.

Consulting:

  • BioMarin Pharmaceutical Inc.

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.

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Address

Icahn Medical Institute Floor 14 Room 14-26A (Lab)
1425 Madison Avenue
New York, NY 10029


Address

Icahn Medical Institute Floor 14 Room 14-25
1425 Madison Avenue
New York, NY 10029

Tel: 212-659-6738