Calogera M Simonaro, PhD
- RESEARCH PROFESSOR | Genetics and Genomic Sciences
Research Topics:Apoptosis/Cell Death, Biomechanics/Bioengineering, Bone Biology, Cartilage Biology, Cellular Differentiation, Cytokines, Genetics, Inflammation, Lysosomal Storage Diseases, Pathology
BA, St. John's University
MS, Brooklyn College
PhD, New York University
Mount Sinai School of Medicine
MPh, New York University
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.