Our laboratory is interested in the differentiation, function, and activation of cells of the myeloid lineage that are important in innate immunity and autoimmune/inflammatory diseases. These cells include macrophages and dendritic cells (DCs) that activate immune/inflammatory responses and osteoclasts that mediate inflammatory bone loss (osteolysis). These cells are regulated by soluble proteins termed cytokines that trigger signal transduction and gene activation cascades. Recent breakthroughs in the treatment of autoimmune/inflammatory diseases have arisen from biological therapies that target myeloid cells and cytokines.
We study crosstalk among major myeloid cell signal transduction pathways, with an emphasis on the Janus kinase ? signal transducer and activator of transcription (Jak-STAT) pathway that is utilized by many cytokines. We are delineating molecular mechanisms by which activating inputs from Jak-STAT, Toll-like receptor, and ITAM-dependent signaling pathways are integrated to activate cell effector functions. We study the functional relationships between signaling events and downstream effects on gene expression, cell function, and the severity of inflammation and related tissue damage. We are also interested in understanding how the production and function of homeostatic/suppressive cytokines (such as IL-10) are regulated. We are developing the idea that dynamic modulation or ?reprogramming? of cytokine signaling during innate immunity and inflammation is an important determinant of the balance of cytokine action and the extent and nature of immune and inflammatory reactions.
The laboratory takes an integrated bench to bedside approach and studies signal transduction defects in defined in vitro systems using purified cells, in animal models of arthritis, lupus and osteolysis, and in human disease samples. Biochemical approaches are complemented by genetic approaches that utilize RNA interference or knockout mice, and by microarray analysis of genome-wide gene expression. The long term goals of our laboratory are to define the molecular basis of the regulation of cytokine signaling during innate immunity and inflammation, and to target signaling pathways as a novel approach to therapy.
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(212) 606-1653 
(212) 774-2337
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