RESEARCH PROGRAMS AND AFFILIATIONS
Skeletal development, maturation and maintenance; Mesenchymal stem cell biology; Radiobiology of skeletal tissues; Radiosensitization of pediatric musculoskeletal sarcoma.
ASSOCIATIONS / MEMBERSHIPS
Skeletal development, maturation and maintenance: The structures that form the skeleton arise very early in embryonic development, continue to grow during childhood, and are actively remodeled throughout our lives. My research in this area focuses on how intercellular signaling between bone forming osteoblasts, bone resorbing osteoclasts, hematopoietic and vascular cells, along with input from systemic endocrine stimuli, collaboratively regulate bone integrity. Perturbation of these signaling circuits can lead to variety of structural and metabolic bone diseases, such as osteoporosis, and can result in fractures. Greater understanding of signaling within this bone microenvironment may translate to new strategies to prevent or correct bone disease.
Mesenchymal stem cell biology: Mesenchymal stem cells (MSCs) derive from the embryonic mesoderm and give rise to the connective tissues throughout the body. Lineage restricted derivatives of these cells persist through post-natal growth, and function in maintenance and repair of connective tissues throughout our life span. Whether these MSC's persist post-natally as truly, multipotent 'stem cells' is unresolved due to a lack of sufficiently specific molecular markers, which identify these cells in situ. My research in this area focuses on identifying the factors that specify differentiation of MSC and their post-natal derivatives, toward the bone, cartilage, and adipose lineages. Better understanding of the biology of these cells will enhance our ability to identify these cells, and may facilitate the use of such cells in therapeutic applications.
Radiobiology of skeletal tissues: Ionizing radiation is used in the treatment of many solid cancers, but can cause collateral damage to healthy tissues surrounding the targeted tumor. Occasionally, irradiation of skeletal structures is unavoidable, and can result in localized radiation-induced bone disease, and elevated susceptibility to atraumatic fracture. My research in this area will study the radiobiologic response of the bone microenvironment, to determine the mechanisms that result in persistent osteogenitor depletion and replacement of hematopoietic marrow with adipose tissue. The goal of this line of research is to develop strategies which prevent or repair bone damage resulting from radiation exposure, and minimize the impact of radiation-induced bone disease on the quality of life of cancer survivors.
Radiosensitization of pediatric musculoskeletal sarcoma: Sarcomas are a family of cancers that develop in connective tissues such as the muscle or bone. Ewing's sarcoma and rhabdomyosarcoma, which develop in bone and muscle respectively, are pediatric cancers with a tendency to occur adjacent to areas of active bone growth. In addition to surgery and chemotherapy, ionizing radiation is used to treat these cancers, but may result in permanent damage to growing bone including asymmetric growth arrest, angular deformity and increased susceptibility to fracture. The severity of bone injury is largely determined by the dose of radiation that the bone receives. Therefore it is reasoned that strategies which selectively sensitize tumor tissue to radiation could lower the dose of radiation needed to achieve local control, and minimize collateral injury of adjacent healthy tissue.