Degranulation deconstructed.

Pediatricians first described the clinical features of chronic granulomatous disease (CGD) in 1959. Almost a decade later, in a collaborative effort that crossed disciplines, we participated in the discoveries that defined the cellular deficiencies of CGD, specifically finding that improper degranulation of leukocytes did not explain their failure to fight pathogens, rather that the fundamental defect was due to problems in the unique NADPH oxidase system of phagocytizing leukocytes. In the years that followed, the subunit components and structure of NADPH oxidase and their translocation during leukocyte phagocytosis to form the active enzyme were well described, leading to the identification of the component genes, the mapping of their chromosomal locations, and their subsequent cloning.

Quantitative proteomic analysis of fibroblast nuclear proteins after stimulation with mitogen activated protein kinase inhibiting heparan sulfate.

Certain structures of heparan sulfate (HS) inhibit cell proliferation of fibroblasts. Whether this inhibition is dependent on inhibition of mitogenic signaling pathways or nuclear translocation of HS is unknown. In this study we investigated possible mechanism(s) and structural requirements by which antiproliferative glycosaminoglycans exert their effects on mitogen-activated protein kinase (MAP kinase) phosphorylation, a key intermediate in cell signaling, followed by quantitative proteomic analysis of nuclear proteins by stable isotope coded affinity tags, multidimensional chromatography and tandem mass spectrometry.

Increased MMP-2 expression in connective tissue growth factor over-expression vascular smooth muscle cells.

Connective tissue growth factor (CTGF) is abundantly expressed in the vascular smooth muscle cells (VSMC) of atherosclerotic lesions but not in normal vessels. CTGF is able to promote VSMC proliferation and migration and influences the composition of extracellular matrix. The mechanisms for controlling these events remain unclear.