Calogera M Simonaro, PhD

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.