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My research interests are in bone cell biology. Bone is a dynamic
tissue that is continually remodeled and renewed throughout life,
and it serves as a structural framework for the body, physiological
reservoir for minerals, and the birthplace of hematopoietic cells in
the marrow. To fulfill these functions, the activities of
bone-degrading osteoclasts and bone-forming osteoblasts are normally
precisely balanced. However, this homeostasis is disturbed in diseases
such as osteoporosis, osteopetrosis, Paget’s, rheumatoid arthritis,
periodontal disease, or certain cancers, and the consequent effects
can be severe to life-threatening.
We are particularly interested in the osteoclast (Oc)-related phase
of this coupled bone resorption/formation process and have been studying
how Oc form within bone, what special attributes of an Oc enable only
this cell type to resorb bone, and what circulating or local signals
control Oc development, function, and survival. Recently, we have focused
on how endothelial cells lining the vasculature of bone directly regulate
Oc formation and resorption through their expression of cell-associated
and soluble signals. Our goal is to learn how precursor cells in the
circulation become attracted to and migrate through blood vessels to give
rise to Oc within bone, what signals initiate or mediate this, and what
determines how many Oc will form or where bone will be resorbed and rebuilt
in normal and disease states. Our work indicates that certain cytokines,
chemokines, free radicals, cell adhesion molecules, proteolytic enzymes,
and other specific signaling molecules are important in these events. This
research is being conducted in collaboration with Dr. Philip Osdoby in Biology
and employs a wide variety of tissue culture, immunological, microscopic,
biochemical, molecular, and functional (resorption) assays.
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Section of human bone stained with the antibody RANKL to show that activated vascular endothelial cells and bone-forming osteoblasts express this important regulatory molecule responsible for causing the formation of bone-resorbing osteoclasts.
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