Venkatesh Sampath, MD, MRCPCH
Dr. Venkatesh Sampath's research focuses on the role of innate immune receptors in the causation of diseases of preterm infants. Toll-like receptors (TLR) are pathogen recognition receptors which are pivotal for mediating specific, innate immune responses against a host of bacterial and viral ligands. Altered TLR signaling plays an important role in many diseases like a sepsis, chronic mucosal inflammation, ARDS and possibly in atherosclerosis. We are using translational and basic science approaches to examine the pathogenesis of bronchopulmonary dysplasia (a debilitating chronic lung disease) and sepsis in preterm infants in the context of alterations in TLR signaling.
Sequence variation in TLRs and diseases of prematurity. This multi-center project involves genotyping preterm infants for SNPs in the TLR pathway genes to determine whether hypomorphic/hypermorphic variants alter susceptibility to diseases like bronchopulmonary dysplasia and sepsis in the preterm infant. Additionally, we will assess whether said variants alter the inflammatory response to TLR ligands using cell-culture approaches and cord-blood monocyte assays.
Basic Science Focus
Mechanisms underlying TLR-mediated oxidative stress in BPD. This project examines the mechanisms and implications of TLR mediated oxidative stress in primary human lung endothelial cells. We believe that lipopolysaccharide (LPS) mediated endothelial injury is critical to the pathogenesis of lung disease in premature infants. We are investigating interactions between NADPH oxidases and TLRs that mediate oxidative stress and endothelial injury using a cell-culture model. Additionally, the effect of environmental oxygen tension on these interactions in BPD is being examined.
Sampath V, Radish AC, Eis AL, Broniowska K, Hogg N, Konduri GG. Attenuation of lipopolysaccharide-induced oxidative stress and apoptosis in fetal pulmonary artery endothelial cells by hypoxia. Free Radical Biol Med. 2009 Mar 1; 46(5):663-71.
Altered postnatal lung development in C3H/HeJ (tlr4 Lps-d) mice. Venkatesh Sampath, Katy Davis, Albert P Sent, Theresa B Richardson; Joseph A Kitzmiller, Pierre Y Berclaz, Thomas R Korfhagen. Pediatr Res. 2006 Dec; 60(6):663-8.
The fetal origins hypothesis – implications for the 21st century. Sampath V. Indian Journal of Practical Pediatrics. Nov 2005.
Non-immune Hydrops Fetalis and Fulminant Disease due to Congenital Cytomegalovirus Infection in a Premature Infant. Sampath V, Narendran V, Donovan EF, Stanek J and Schleiss M. J Perinatol. 2005 Sep; 25(9):608-11.
Risk Factors for Adverse Neurodevelopment in Extremely Low Birth Weight infants with Normal Neonatal Cranial Ultrasound. Sampath V. Bowen J, Gibson F. Journal of Perinatology. 2005 Mar; 25(3):210-215.
Publications as listed in PubMed