The main focus of the research in my laboratory is on the cellular events that regulate pro-inflammatory gene expression and Reactive Oxygen Species (ROS) production in vascular cells.

1. We study the transcription factor NF-kappaB in regulating expression pro-inflammatory genes. Due to the vast variety of activating signals and target genes, NF-kappaB has often been named ?the master switch of immune response?. While there are several Rel family members, the p50 and p65 subunits are most ubiquitously expressed and p65 shows the highest transcriptional activity of all subunits on most genes tested. We analyze the role protein phosphorylation of the p65 subunit in activating and repressing NF-kappaB activity and try to define protein kinase modules that are involved in such regulation.

We are interested in the transcriptional regulation of NADPH oxidase subunits. NADPH oxidase is a multiprotein complex that contributes to cellular superoxide production. While highly expressed in macrophages and neutrophiles where the enzyme complex is an integral part of the innate immunity response to kill pathogens, it is also expressed at lower levels in several other cell types including endothelial, vascular smooth muscle cells and neurons. In these cells, NADPH oxidase is integrated in several signaling pathways most prominently in the Angiotensin II signaling cascade leading to a changed vascular gene expression profile that has been linked to vasculopathies in chronic hypertension and development of arteriosclerosis. In our laboratory we study the transcriptional regulation of several NADPH oxidase subunits in endothelial cells and macrophages. We hypothesize that specific transcriptional activation and repression of components of the Angiotensin II-NADPH oxidase system might change the cellular response in pathologic condition such as hypertension and arteriosclerosis and contribute to the disease process.

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