Projects per year
Personal profile
Personal profile
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.
Research interests
Dr. Le's research focuses on mechanisms by which atherosclerotic plaques are dominantly formed in areas of blood vessel wall that are exposed to disturbed flow (d-flow) but rarely formed in areas of blood vessel wall that are exposed to laminar flow (l-flow). Previously, Dr. Le's group demonstrated that in endothelial cells (ECs), the increased p90RSK activity promotes EC activation, dysfunction, apoptosis, and senescence, all of which are acting in concert, which ultimately promotes atherosclerotic plaque formation in areas where blood vessel are exposed to d-flow. Particularly, d-flow-mediated p90RSK activation causes EC dysfunction and atherosclerosis via downregulating the anti-inflammatory and anti-atherogenic effect of ERK5, a kinase with transcriptional activity domain that also plays an important role in the anti-inflammatory effect of statins in heterotopic heart transplantation mouse model. Once activated, p90RSK binds SENP2 and phosphorylates SENP2 T368, the cellular event that triggers SENP2 nuclear export, and consequently results in the increased SUMOylation of ERK5 and p53 and thus atherosclerosis. Simultaneously, the activated p90RSK directly binds to, and phosphorylates telomeric repeat-binding factor 2-interacting protein (TERF2IP) at S205 residue, the cellular event that is required for the TERF2IP-TRF2 complex nuclear export. An unbiased transcriptome analysis demonstrated that under d-flow-mediated p90RSK activation, TERF2IP S205A phosphorylation alters the expression of a distinct set of genes, including rapamycin-insensitive companion of mTOR (RICTOR) and makorin-1 (MKRN1) ubiquitin E3 ligase, leading to EC activation, senescence (increased telomere shortening, p53, p21 expression, decreased telomerase induction), apoptosis, and atherosclerosis. Recently, Dr. Le's group reported that various drugs including the combination antiretroviral therapy (cART) used in HIV therapies, ionizing radiation (IR) and ponatinib used in cancer therapies also can induce p90RSK activation, which “prime” the cells to the secondary toxicity insults, leading to the sustained chronic inflammation. Sharing the common signaling pathway with d-flow, IR and ponatinib increases ERK5 SUMOylation, promoting EC activation and inflammation, the events that are known to increase atherosclerosis. Because both d-flow and IR are strongly associated with an increased risk of atherosclerosis and cardiovascular diseases, both d-flow and IR share common signaling pathways that are involved in atherosclerosis and cardiovascular diseases, the major goal of current studies is to investigate mechanisms by which radiotherapy used in cancer treatment can lead to cardiovascular diseases even 5-10 years later.
External positions
Associate Professor of Vascular Biology in Cardiothoracic Surgery, Weill Cornell Medical College
Jul 1 2012 → …Free-text keywords
- Atherosclerosis
- Endothelial cell function
- Disturbed flow
- Cardio-oncology
Research Area Keywords
- Molecular Medicine
- Immunobiology & Inflammation
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Projects
- 2 Active
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Pathological flow-induced endothelial damage and plaque erosion
7/15/19 → 6/30/23
Project: Federal Funding Agencies
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A Novel Role for MAGI1 in regulating non-canonical LATS signaling and atherosclerotic plaque formation
1/1/18 → 2/28/22
Project: Federal Funding Agencies
Research output
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SARS-CoV-2 Mediated Endothelial Dysfunction: The Potential Role of Chronic Oxidative Stress
Chang, R., Mamun, A., Dominic, A. & Le, N. T., Jan 15 2021, In : Frontiers in Physiology. 11Research output: Contribution to journal › Review article
Open Access -
Bone marrow transplantation platform to investigate the role of dendritic cells in graft-versus-host disease
Nguyen, H. D., Huong, P. T., Hossack, K., Gurshaney, S., Ezhakunnel, K., Huynh, T. H., Alvarez, A. M., Le, N. T. & Luu, H. N., Mar 2020, In : Journal of Visualized Experiments. 2020, 157, e60083.Research output: Contribution to journal › Article
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p90RSK-MAGI1 Module Controls Endothelial Permeability by Post-translational Modifications of MAGI1 and Hippo Pathway
Abe, R. J., Savage, H., Imanishi, M., Banerjee, P., Kotla, S., Paez-Mayorga, J., Taunton, J., Fujiwara, K., Won, J. H., Yusuf, S. W., Palaskas, N. L., Banchs, J., Lin, S. H., Schadler, K. L., Abe, J. & Le, N-T., Nov 13 2020, In : Frontiers in Cardiovascular Medicine. 7, p. 255 1 p.Research output: Contribution to journal › Article
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Time-dependent replicative senescence vs. disturbed flow-induced pre-mature aging in atherosclerosis
Dominic, A., Banerjee, P., Hamilton, D. J., Le, N-T. & Abe, J. I., Oct 2020, In : Redox Biology. 37, 101614.Research output: Contribution to journal › Review article
3 Scopus citations -
Cancer Treatment (CTCT) Promotes Oxidative Stress and Alters Monocyte/ macrophage Biology
Kotla, S., Zhang, A., Ae Ko, K., Imanishi, M., Mazhar, H., Thomas, T., Gi, Y., Vu, H. T., Krishnan, S., McBeath, E., Lin, S., Kleinerman, E., Schadler, K., Fujiwara, K., Gupte, A. A., Le, N-T., Hamilton, D. J. & Abe, J. I., Dec 2019, In : Free Radical Biology and Medicine. 145, S1, p. S134Research output: Contribution to journal › Conference article