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.
- MKK3 regulates mitochondrial biogenesis and mitophagy in sepsis induced lung injury. Mannam P, Shinn ASS, Srivastava A, Neamu RF, Walker WE, Bohanon M, Merkel J, Kang MJ, Dela Cruz CS, Ahasic AM, Pisani MA, Trentalange A, West AP, Shadel GS, Shen J, Elias JA, Lee PJ. Am J Physiol Lung Cell Mol Physiol. 2014
- Macrophage Migration Inhibitory Factor Deficiency in Chronic Obstructive Pulmonary Disease. Sauler M, Leng L, Trentalange M, Haslip M, Shan P, Piecychna M, Zhang Y, Andrews N, Allore H, Fried T, Mannam P, Bucala R, Lee PJ. Am J Physiol Lung Cell Mol Physiol. 2014
- Endothelial MKK3 is a critical mediator of lethal murine endotoxemia and acute lung injury. Mannam P, Zhang X, Shan P,Zhang Z, Shinn AS, Zhang Y, Lee PJ.mJournal of Immunology 2013, 190(3).
- Analytic review: management of life-threatening asthma in adults. Mannam P, Siegel MD. J Intensive Care Med. 2010 Jan-Feb;25(1):3-15.
- Successful Treatment of Chylous Ascites Secondary to Sarcoidosis with Methotrexate. Mannam P, Boselli JM, Schulman ES. Hosp Pract (Minneap). 2009 Dec;37(1):144-6.
- Pulmonary Hypertension in the Elderly: More Common Than We Thought? Mannam P, Trow TK. Clinical Pulmonary Medicine. 14(4):240-242, July 2007.
- Mucosal vaccine made from live, recombinant Lactococcus lactis protects mice against pharyngeal infection with Streptococcus pyogenes. Mannam P, Jones KF, Geller BL. Infect Immun. 2004 Jun; 72(6):3444-50.
- Innate Immunity During REM Sleep Deprivation. Anand Sivaprakash RM, Mathew Jeraud, Mannam P, Sheela Devi R, Namasivayam A. Biomedicine. 2001, 21(1): 41-45.