Harvard Catalyst Profiles

My laboratory studies skeletal and vascular morphogenesis, growth and remodeling/repair. Work is currently directed at three project areas.

In the first project we study skeletal morphogenesis and growth. We are interested in genes that control differentiation of mesenchymal cells to chondrocytes and osteoblasts, the control of spatial patterns of mesenchymal condensations during skeletal development, the molecular mechanisms controlling the formation of ossification centers, the regulation of proliferation and differentiation of chondrocytes in growth plates, and molecular mechanisms responsible for accrual of bone mass and remodeling of the vertebrate skeleton in response to mechanical stress. In addition to using knock-out, knock-in, and conditional knock-out mice in studies of specific genes, we make extensive use of genetic approaches in mice and humans. This includes mapping of inherited disorders, gene identification and mutation detection.

In the second project we investigate the molecular basis for vascular morphogenesis, using a combination of human genetics and studies of cells in culture. In addition, we study mice with inactivated alleles for collagens that are expressed in vascular walls, and use conditional knock-out techniques to inactivate VEGF and its receptors in mice.

In the third project we are studying genetic causes of degenerative joint disease (osteoarthritis) in humans and mice. One approach involves identification of mutations responsible for early-onset osteoarthritis as part of inherited osteochondrodysplasias and cellular/molecular analyses of pathogenetic mechanisms.