Nhat Tu Le, Ph.D.

Nhat Tu Le, Ph.D.

Contact Information

Aab Cardiovascular Research Institute
211 Bailey Road
West Henrietta, NY 14586

Research Bio

Disturbed flow of blood (d-flow) is known to contribute to atherosclerosis. However the unique underlying molecular mechanisms mediating this process are not well understood. As such, answering the question of how d-flow leads to atherosclerosis is critical and will have broad implications in endothelial biology, endothelial dysfunction and cardiovascular diseases.



My career goal is to discover treatments for diabetes-related complications of cardiovascular diseases. Diabetes is on the rise worldwide. It is a common condition that contributes to illness, disability and early death. Every year, billion U.S. dollars are spent on the disease, yet more than 200,000 people die as a result of this disease. A combination of risk factors such as diabetes and obesity creates a pro-inflammatory environment that leads to endothelial inflammation and dysfunction. This endothelial dysfunction is exacerbated by d-flow.

I am interested in the molecular mechanisms that cause endothelial cell dysfunction, and subsequently, atherosclerosis formation. Recently, I have used a combination of in vitro molecular, cellular, and biochemical approaches, together with in vivo and ex vivo approaches, including en face confocal microscopy and intravital microscopy to identify the mechanisms that contribute to endothelial dysfunction. These approaches have allowed me to identify a critical role for p90RSK activation in endothelial inflammation, dysfunction and atherosclerosis formation.

Currently, my research focus is on the upstream regulator of p90RSK: Syk, and its downstream target: MAGI-1. I am testing the hypothesis that d-flow uniquely mediates PECAM1/Syk activation in EC in atheroprone areas that elevates p90RSK activation, which increases MAGI-1 phosphorylation and decreases MAGI-1-SUMOylation, thereby promoting EC dysfunction and atherosclerosis. The successful completion of this study will provide novel insights into the molecular mechanism by which Syk-p90RSK-MAGI-1 signaling accelerates EC dysfunction, which might reveal promising targets and strategies for prevention and treatment of endothelial dysfunction associated diseases such as atherosclerosis and heart failure. This study will allow me to use the skills and techniques that I acquired during my graduate and postdoctoral work to solidify my independent research program, and to further my career goal of identifying the mechanisms that promotes endothelial inflammation, dysfunction and subsequent atherosclerosis, especially in diabetes.

Awards & Honors (National)

Scientist Development Grant (SDG) Award (PI) | American Heart Association 2013 - 2016
The Melvin L. Marcus Young Investigator Award Finalist | Council on Basic Cardiovascular Sciences 2011
Invited speaker at Keystone symposia on | Keystone 2011
AHA Postdoc Fellowship Award (PI) | AHA 2009 - 2011

Recent Journal Articles

Showing the 5 most recent journal articles. 9 available »

2013 Feb
Heo KS, Chang E, Takei Y, Le NT, Woo CH, Sullivan MA, Morrell C, Fujiwara K, Abe JI. "Phosphorylation of protein inhibitor of activated STAT1 (PIAS1) by MAPK-activated protein kinase-2 inhibits endothelial inflammation via increasing both PIAS1 transrepression and SUMO E3 ligase activity." Arteriosclerosis, thrombosis, and vascular biology.. 2013 Feb; 33(2):321-9. Epub 2012 Nov 29.
2013 Jan 29
Le NT, Heo KS, Takei Y, Lee H, Woo CH, Chang E, McClain C, Hurley C, Wang X, Li F, Xu H, Morrell C, Sullivan MA, Cohen MS, Serafimova IM, Taunton J, Fujiwara K, Abe JI. "A crucial role for p90RSK-mediated reduction of ERK5 transcriptional activity in endothelial dysfunction and atherosclerosis." Circulation.. 2013 Jan 29; 127(4):486-99. Epub 2012 Dec 14.
2012 Feb 17
Le NT, Takei Y, Shishido T, Woo CH, Chang E, Heo KS, Lee H, Lu Y, Morrell C, Oikawa M, McClain C, Wang X, Tournier C, Molina CA, Taunton J, Yan C, Fujiwara K, Patterson C, Yang J, Abe JI. "p90RSK targets the ERK5-CHIP ubiquitin E3 ligase activity in diabetic hearts and promotes cardiac apoptosis and dysfunction." Circulation research.. 2012 Feb 17; 110(4):536-50. Epub 2012 Jan 19.
2012
Le NT, Corsetti JP, Dehoff-Sparks JL, Sparks CE, Fujiwara K, Abe J. "Reactive Oxygen Species, SUMOylation, and Endothelial Inflammation." International journal of inflammation. 2012 2012:678190. Epub 2012 Sep 06.
2011 May 30
Heo KS, Lee H, Nigro P, Thomas T, Le NT, Chang E, McClain C, Reinhart-King CA, King MR, Berk BC, Fujiwara K, Woo CH, Abe J. "PKC? mediates disturbed flow-induced endothelial apoptosis via p53 SUMOylation." The Journal of cell biology. 2011 May 30; 193(5):867-84.

Current Appointments

Research Assistant Professor - Department of Medicine, Aab Cardiovascular Research Institute (SMD) - Primary

Education

PhD | Microbiology | Sungkyunkwan University, South Korea2008