Arshad Rahman, Ph.D.

My laboratory has a long-standing interest in endothelial cell biology and lung physiology especially as it relates to molecular analysis of signal transduction and gene regulation, and in vivo gene delivery to the lung endothelium. Specifically, we want to know how the otherwise "antiadhesive, anticoagulant, and relatively restrictive (semipermeable)" microvasculature is rendered into a "proadhesive, procoagulant, and leaky" one during acute lung injury (ALI). We have made contributions to the understanding of regulation of nuclear factor-kappaB (NF-?B), a master regulator of inflammation that is implicated in regulating these phenotypes of microvasculature during ALI and other inflammatory conditions. Another area of my research focuses on understanding the regulation and function of endothelial cells (EC) autophagy and its relationship with EC inflammation in the context of ALI. Our novel and exciting findings that autophagy and inflammation are linked in the lung endothelium and collaborate in causing lung injury form the basis of our ongoing research to identify the mechanistic link between these two fundamental processes (autophagy and inflammation), and address the relevance of this linkage in the pathogenesis of ALI.

More recently, we have been focusing on Spleen Tyrosine Kinase (Syk) and Mechanistic/Mammalian Target of Rapamycin (MTOR) as critical mechanistic targets for modulation of ALI pathogenesis. The Syk project seeks to clarify the mechanism by which Syk regulates EC dysfunction (permeability and inflammation) in ALI and evaluate the therapeutic efficacy of Syk inhibition against evolving ALI in mice with sepsis. The MTOR project builds logically on our prior work and seeks to clarify the role of MTOR in ALI and evaluate the preventive and therapeutic efficacy of modulation of MTOR signaling against ALI. In a nutshell, the research in my lab uses genetically modified mice, primary cell cultures, and multidisciplinary approaches ranging from biochemical, cellular, and molecular biology to in vivo gene delivery (cell-specific transfer of genes and shRNA to endothelial cells in the lung) and multiple mouse models of ALI to identify viable therapeutic targets and mechanisms to limit ALI.