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Nhat-Tu Le, PhD

Associate Professor of Cardiovascular Sciences, Institute for Academic Medicine
Associate Member, Research Institute
Houston Methodist
Weill Cornell Medical College


Biography

Dr. Nhat-Tu Le earned Bachelor and Master of Science degrees in microbiology from the University of Science in Ho Chi Minh City, Vietnam.  In 2008 she completed her PhD, also in microbiology, at Sungkyungkwan University College of Pharmacy in South Korea. The focus of her PhD training was to understand the roles of the Streptococcus pneumoniae heat shock protein ClpL in pneumococcal adherence to host cells. Her first study was published in 2007, describing the effects of Streptococcus pneumoniae heat shock protein ClpL (Caseinolytic protease L) in pathogenesis and translocation of virulence factors.  Dr. Le’s postdoctoral training was under the guidance of Dr. Jun-ichi Abe at the University of Rochester studying the role of endothelial p90RSK-ERK5 complex in the heart and the vessel. Before joining Houston Methodist in July of 2017, Dr. Le was an assistant professor at MD Anderson Cancer Center since 2014.

Description of Research

Many agents used in cancer treatment result in significant vascular complications such as angina, myocardial infarction, venous or arterial thrombosis, and newly developed or worsened hypertension. These events are caused by the dysfunction of endothelial cells including apoptosis, inflammation, and decreased NO production. Nhat Tu Le’s research group has developed various systems to examine disturbed flow-induced signaling both in vitro and in vivo, and found the formation of a pro-inflammatory and pro-Senescence complex consisting of p90RSK, shelterin complex member, and p65. They have also found that endothelial ERK5 plays a role in regulating statin-induced anti-inflammatory effect using the mouse heart transplantation model. Recently, she discovered MAGI1 (the membrane-associated guanylate kinase-1) as an unexplored molecule that regulates both endothelial inflammation and anti-viral response. Our long-term goal is to establish an “Onco-cardiology” research field at the Houston Methodist Research Institute.

Publications

Regulation of Kir2.1 Function Under Shear Stress and Cholesterol Loading
Le, N-T & Abe, J-I 2018, Journal of the American Heart Association, vol. 7, no. 5. DOI: 10.1161/JAHA.118.008749

Induction of the pneumococcal vncRS operon by lactoferrin is essential for pneumonia
Ghosh, P, Kwon, H, Park, S-S, Kim, G-L, Choi, S-Y, Kim, E-H, Tran, TD-H, Seon, SH, Le, NT, Iqbal, H, Lee, S, Pyo, S & Rhee, D-K 2018, Virulence, vol. 9, no. 1, pp. 1562-1575. DOI: 10.1080/21505594.2018.1526529

Ionizing Radiation Induces Endothelial Inflammation and Apoptosis via p90RSK-Mediated ERK5 S496 Phosphorylation
Vu, HT, Kotla, S, Ko, KA, Fujii, Y, Tao, Y, Medina, J, Thomas, T, Hada, M, Sood, AK, Singh, PK, Milgrom, SA, Krishnan, S, Fujiwara, K, Le, N-T & Abe, J-I 2018, Frontiers in cardiovascular medicine, vol. 5, pp. 23. DOI: 10.3389/fcvm.2018.00023

Ponatinib Activates an Inflammatory Response in Endothelial Cells via ERK5 SUMOylation
Paez-Mayorga, J, Chen, AL, Kotla, S, Tao, Y, Abe, RJ, He, ED, Danysh, BP, Hofmann, M-CC & Le, N-T 2018, Frontiers in cardiovascular medicine, vol. 5, pp. 125. DOI: 10.3389/fcvm.2018.00125

Sub-cellular localization specific SUMOylation in the heart
Le, N-T, Martin, JF, Fujiwara, K & Abe, J-I 2017, Biochimica et Biophysica Acta - General Subjects, vol. 1863, no. 8, pp. 2041-2055. DOI: 10.1016/j.bbadis.2017.01.018

Endothelial-to-Osteoblast Conversion Generates Osteoblastic Metastasis of Prostate Cancer
Lin, SC, Lee, YC, Yu, G, Cheng, CJ, Zhou, X, Chu, K, Murshed, M, Le, NT, Baseler, L, Abe, JI, Fujiwara, K, deCrombrugghe, B, Logothetis, CJ, Gallick, GE, Yu-Lee, LY, Maity, SN & Lin, SH 2017, Developmental Cell, vol. 41, no. 5, pp. 467-480.e3. DOI: 10.1016/j.devcel.2017.05.005

Flow signaling and atherosclerosis
Le, N-T, Sandhu, UG, Quintana-Quezada, RA, Hoang, NM, Fujiwara, K & Abe, J-I 2017, Cellular and Molecular Life Sciences, vol. 74, no. 10, pp. 1835-1858. DOI: 10.1007/s00018-016-2442-4

Coordination of Cellular Localization-Dependent Effects of Sumoylation in Regulating Cardiovascular and Neurological Diseases
Abe, J-I, Sandhu, UG, Hoang, NM, Thangam, M, Quintana-Quezada, RA, Fujiwara, K & Le, NT 2017, Advances in Experimental Medicine and Biology, vol. 963, pp. 337-358. DOI: 10.1007/978-3-319-50044-7_20

Role for SUMOylation in disturbed flow-induced atherosclerotic plaque formation
Abe, JI, Le, NT & Heo, KS 2015, Biomedical Engineering Letters, vol. 5, no. 3, pp. 162-171. DOI: 10.1007/s13534-015-0199-6

Platelet Extracellular Regulated Protein Kinase 5 Is a Redox Switch and Triggers Maladaptive Platelet Responses and Myocardial Infarct Expansion
Cameron, SJ, Ture, SK, Mickelsen, D, Chakrabarti, E, Modjeski, KL, McNitt, S, Seaberry, M, Field, DJ, Le, N-T, Abe, J-I & Morrell, CN 2015, Circulation, vol. 132, no. 1, pp. 47-58. DOI: 10.1161/CIRCULATIONAHA.115.015656

Disturbed flow-activated p90RSK kinase accelerates atherosclerosis by inhibiting SENP2 function
Heo, K-S, Le, N-T, Cushman, HJ, Giancursio, CJ, Chang, E, Woo, C-H, Sullivan, MA, Taunton, J, Yeh, ETH, Fujiwara, K & Abe, J 2015, The Journal of clinical investigation, vol. 125, no. 3, pp. 1299-310. DOI: 10.1172/JCI76453

Erratum for Le et al., Modulation of Adherence, Invasion, and Tumor Necrosis Factor Alpha Secretion during the Early Stages of Infection by Streptococcus pneumoniae ClpL
Le, N-T, Jeong, H-Y, Kwon, H-Y, Ogunniyi, AD, Paton, JC, Pyo, S-N & Rhee, D-K 2015, Infection and Immunity, vol. 83, no. 3, pp. 1224. DOI: 10.1128/IAI.03125-14

Identification of activators of ERK5 transcriptional activity by high-throughput screening and the role of endothelial ERK5 in vasoprotective effects induced by statins and antimalarial agents
Le, N-T, Takei, Y, Izawa-Ishizawa, Y, Heo, K-S, Lee, H, Smrcka, AV, Miller, BL, Ko, KA, Ture, S, Morrell, C, Fujiwara, K, Akaike, M & Abe, J 2014, Journal of Immunology, vol. 193, no. 7, pp. 3803-15. DOI: 10.4049/jimmunol.1400571

Streptococcus pneumoniae ClpL modulates adherence to A549 human lung cells through Rap1/Rac1 activation
Nguyen, CT, Le, N-T, Tran, TD-H, Kim, E-H, Park, S-S, Luong, TT, Chung, K-T, Pyo, S & Rhee, D-K 2014, Infection and Immunity, vol. 82, no. 9, pp. 3802-10. DOI: 10.1128/IAI.02012-14

De-SUMOylation enzyme of sentrin/SUMO-specific protease 2 regulates disturbed flow-induced SUMOylation of ERK5 and p53 that leads to endothelial dysfunction and atherosclerosis
Heo, K-S, Chang, E, Le, N-T, Cushman, H, Yeh, ETH, Fujiwara, K & Abe, J 2013, Circulation research, vol. 112, no. 6, pp. 911-23. DOI: 10.1161/CIRCRESAHA.111.300179

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
Heo, K-S, Chang, E, Takei, Y, Le, N-T, Woo, C-H, Sullivan, MA, Morrell, C, Fujiwara, K & Abe, J 2013, Arteriosclerosis, thrombosis, and vascular biology, vol. 33, no. 2, pp. 321-9. DOI: 10.1161/ATVBAHA.112.300619

A crucial role for p90RSK-mediated reduction of ERK5 transcriptional activity in endothelial dysfunction and atherosclerosis
Le, N-T, Heo, K-S, Takei, Y, Lee, H, Woo, C-H, 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, J-I 2013, Circulation, vol. 127, no. 4, pp. 486-99. DOI: 10.1161/CIRCULATIONAHA.112.116988

p90RSK targets the ERK5-CHIP ubiquitin E3 ligase activity in diabetic hearts and promotes cardiac apoptosis and dysfunction
Le, N-T, Takei, Y, Shishido, T, Woo, C-H, Chang, E, Heo, K-S, 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, J 2012, Circulation research, vol. 110, no. 4, pp. 536-50. DOI: 10.1161/CIRCRESAHA.111.254730

Reactive Oxygen Species, SUMOylation, and Endothelial Inflammation
Le, N-T, Corsetti, JP, Dehoff-Sparks, JL, Sparks, CE, Fujiwara, K & Abe, J-I 2012, International Journal of Inflammation, vol. 2012, pp. 678190. DOI: 10.1155/2012/678190

PKC? mediates disturbed flow-induced endothelial apoptosis via p53 SUMOylation
Heo, K-S, Lee, H, Nigro, P, Thomas, T, Le, N-T, Chang, E, McClain, C, Reinhart-King, CA, King, MR, Berk, BC, Fujiwara, K, Woo, C-H & Abe, J 2011, Journal of Cell Biology, vol. 193, no. 5, pp. 867-84. DOI: 10.1083/jcb.201010051