Viswanathan Natarajan

I am basic/translational research scientist and the overall goal of my research is to understand molecular mechanisms and signaling pathways that mediate lung inflammation and injury and develop novel therapeutic agents to ameliorate pulmonary leak, lung edema, and restore barrier integrity. Three major areas of focus are: (i) mechanisms of ROS production and role of ROS regulation of pro-inflammatory genes in lung disorders, (ii) Sphingolipids in lung pathologies and intracellular S1P as a co-epigenetic regulator of lung inflammation and injury, and (iii) Role of cardiolipin (CL) and CL remodeling enzyme, lysocardiolipin acyltransferase in development, progression and metastasis of non-small cell lung cancer. The underlying premise is that understanding basis of altered chromatin remodeling by ROS and S1P in different lung pathologies will help to identify signaling targets and develop new pharmacological approaches to restore lung function and integrity. Recently, my group has initiated new and exciting studies on S1P as a co-epigenetic regulator of chromatin remodeling and expression of pro-inflammatory genes in sepsis- and bacteria-mediated lung inflammation and injury. Our preliminary data show that in sepsis-induced lung injury, S1P generated by SphK1 regulated chromatin remodeling while in Pseudomonas aeruginosa infection of the mouse lung, nuclear SphK2 played an important role in H3 and H4 histone acetylation and chromatin remodeling. These data suggest an intriguing role for S1P as a co-epigenetic regulator of cell functions. I have been continuously funded by NIH/HLBI since 1993 to work on mechanisms of lung vascular permeability, including the current P01 HL98050. I have trained more than 30 post-doctoral and pulmonary fellows in my laboratory in the past 20 years. I have the ability and expertise and commitment to the Program Director of this PPG and to ensure that it maintains highest scientific level and integrity. It is anticipated that the outstanding investigations will make novel contributions to facilitate development of new and novel therapeutic approaches to minimize lung injury.

Ebenezer DL, Fu P, Suryadeva V, Natarajan V. Epigenetic regulation of pro-inflammatory cytokine secretion by sphingosine1-phosphate (S1P) in acute lung injury: Role of S1P Lyase. Advances in Biological Regulation, S2212-4926 (16)30044-6. Doi: 10.1016/j.jbior.2016.09.007, 2016.

Fu P, Ebenezer DL, Berdyshev EV, Bronova IA, Shaaya M, Harijith A, Natarajan V. Role of Sphingosine Kinase 1 and S1P Transporter Spns2 in HGF-mediated lamellipodia formation in lung endothelium. Journal of Biological Chemistry, 291: 27187-27203, 2016

Jiang Y, Sverdlov MS, Toth PT, Du G, Huang L, Liu Y, Natarajan V, Minshall RD. RalA activation of PLD2-mediated phosphatidic acid production stimulates caveolae-mediated endocytosis and trafficking of endothelial cells. Journal of Biological Chemistry, 291; 20729-20738, 2016.

Ackerman SJ, Park GY, Christman JW, Nyenhuis S, Berdyshev E, Natarajan V. Polyunsaturated lysophosphatidic acid as a potential biomarker. Biomarkers in Medicine, 10: 123-135, 2016.

Black KE, Bain G, Berdyshev E, Castelino FV, Shea BS, Probst CK, Fontaine B, Bronova I, Goulet L, Lagares D, Ahluwalia N, Knipe RS, Natarajan V, Tager AM. Autotaxin activity increases following lung injury, but is not required for LPA production in the lung or for pulmonary fibrosis. FASEB J, 30: 2435-2450, 2016.

Harijith A, Pendyala S, Ebenezer D, Ha A, Fu P, Ma K, Toth P, Berdyshev E, Kanteti P, Natarajan V. Hyperoxia- induced p47phox activation and ROS generation is mediated through S1P transporter Spns2, and S1P/S1P1&2 signaling axis in lung endothelium. Am J Physiol Lung Cell Mol Physiol, 311: L337-L351, 2016.

Hunag L, Berdyshev EV, Tran JT, Xie L, Chen J, Ebenezer DL, Mathew B, Gorshkova I, Zhang W, Reddy SP, Harijith A, Wang G, Feghali-Bostwick C, Noth I, Ma S-F, Zhou T, Ma W, Garcia JGN, Natarajan V. Sphingosine-1-phosphate lyase is an endogenous suppressor of pulmonary fibrosis: Role of S1P signaling and autophagy. Thorax, 70: 1138-1148, 2015.