The first project is the role of gap junction proteins in intercellular communication. We have found that macrophages and lymphocytes express gap junction proteins; we believe that gap junction proteins function as a means of transient intercellular communication in these cells. We are also studying the expression and regulation of gap junction proteins in osteoblastic cells and in insulin-secreting cells.
The second area is the structure and function of macrophage receptors for extracellular ATP. Mouse macrophages express both the recently cloned P2Z and P2U purinergic receptors, and we have evidence for a third receptor we are currently characterizing.
A major area of interest, which encompasses both of the above projects, is the mechanism and function of intercellular calcium waves. These are rises in cytosolic calcium that pass from cell to cell. We have identified intercellular calcium waves in a variety of cell types, and have distinguished three distinct mechanisms by which these waves are propagated: autocrine activity of secreted ATP on P2U purinergic receptors (in macrophages and other cell types); activation of voltage-gated calcium channels by gap-junction mediated ionic traffic (in insulin-secreting cells); and a second gap-junction dependent mechanism that involves calcium influx but is not voltage dependent (in osteoblastic cells).
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