Praveen Mannam MBBS, MS
Assistant Professor of Medicine (Pulmonary)
Innate Immune Mechanisms of Sepsis and Lung Injury
Extensive Research Description
Sepsis is a leading cause of acute lung injury. Sepsis-induced lung injury leads to numerous intensive care units admissions with high mortality and morbidity. Although the outlook has improved with better clinical care there is a need for more research to develop targeted biologic therapies. Endothelial activation and oxidant injury are key events in the pathogenesis of sepsis-induced lung injury. The signaling pathways leading to these events remain poorly defined and are an important area of study. We are investigating the role of MKK3, a mitogen-activated protein kinase signaling molecule, in the pathogenesis of sepsis-induced lung injury. We have recently identified an important role for a novel oxidant-generating enzyme NADPH oxidase 3 (Nox3) in lung and endothelial oxidant generation. Our overall goal is to examine the role of MKK3 in sepsis-induced lung injury and to identify the mechanisms whereby endothelial MKK3 regulates the oxidant milieu. We propose to determine the role of the MKK3 signaling pathway and what we believe to be a novel oxidant pathway, Nox3, in modulating LPS-induced endothelial and tissue injury. Collectively, these insights may lead to new endothelial targeted therapeutic approaches to sepsis-induced lung injury.