Debabrata Patra, PhD

Washington University in St. Louis (WU)

Mammalian skeleton development requires the commitment of mesenchymal stem cells to chondrogenic (cartilage) and osteogenic (bone) lineages and the activation of cartilage and bone specific genes. This commitment requires the interplay of a large number of transcription factors and signaling molecules whose timely regulation determine cell fate and a carefully crafted developmental outcome. My research interests lie in understanding the contributions of a protein called Site-1 Protease to skeletal development and homeostasis. My studies have shown that Site-1 Protease (S1P) is a critical regulator of mammalian skeletal development with crucial roles in cartilage and bone development. I have been systematically investigating the importance of S1P to skeletal development in a progressive set of S1P knock-out mouse models using Col2-Cre, Col2-CreER(T) and Osx-Cre mice. S1P ablation in chondroprogenitor cells via Col2-Cre, the S1Pcko model, demonstrated chondrodysplasia in mice. S1P ablation in the osterix (Osx)-expressing lineage using Osx-Cre results in mice with fragile bones and scoliosis. My research aims to elucidate mechanisms behind these phenotypes and will provide novel insights into the regulation of protein secretory pathways and how their disruptions may lead to clinical phenotypes of skeletal dysplasia, osteopenia, osteoporosis, and kyphoscoliosis.