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. 

Keywords

    Free-text keywords

  • Atherosclerosis, Endothelial cell function, Disturbed flow, Cardio-oncology

    Research Area Keywords

  • Molecular Medicine
  • Immunobiology & Inflammation

Fingerprint

Sumoylation
Concept: Sumoylation
Weight: 100%
Domain: Medicine & Life Sciences
Endothelial Cells
Concept: Endothelial Cells
Weight: 83%
Domain: Medicine & Life Sciences
Apoptosis
Concept: Apoptosis
Weight: 47%
Domain: Medicine & Life Sciences
Atherosclerosis
Concept: Atherosclerosis
Weight: 47%
Domain: Medicine & Life Sciences
Phosphorylation
Concept: Phosphorylation
Weight: 47%
Domain: Medicine & Life Sciences
Ubiquitin-Protein Ligases
Concept: Ubiquitin-Protein Ligases
Weight: 35%
Domain: Medicine & Life Sciences
Mitogen-Activated Protein Kinase 7
Concept: Mitogen-Activated Protein Kinase 7
Weight: 35%
Domain: Medicine & Life Sciences
SUMO-1 Protein
Concept: SUMO-1 Protein
Weight: 33%
Domain: Medicine & Life Sciences
Streptococcus pneumoniae
Concept: Streptococcus pneumoniae
Weight: 33%
Domain: Medicine & Life Sciences
Ubiquitin
Concept: Ubiquitin
Weight: 32%
Domain: Medicine & Life Sciences
Research OutputsResearch Output authored by Nhat-Tu Le is tagged with the concept

Journals

Circulation

ISSNs: 0009-7322, 1524-4539

Lippincott Williams and Wilkins

Journal

3

Infection and Immunity

ISSNs: 0019-9567

American Society for Microbiology

Journal

3

JCI Insight

ISSNs: 2379-3708

Additional searchable ISSN (Electronic): 2379-3708

The American Society for Clinical Investigation

Scopus rating (2018): CiteScore 5.33

Journal

3

Circulation research

ISSNs: 0009-7330

Additional searchable ISSN (Electronic): 1524-4571

Lippincott Williams and Wilkins

Journal

2

Arteriosclerosis, thrombosis, and vascular biology

ISSNs: 1079-5642, 1524-4636

Lippincott Williams and Wilkins

Journal

2
has published Research OutputsResearch Output by Nhat-Tu Le

Research Network

Visualization: Institutional Network

Click on a line in the diagram to see collaboration details.

Click icons to see information about the content.

Nhat-Tu Le

Visualization: Co-author Network

Click on a line in the diagram to see collaboration details.

Click icons to see information about the content.

Nhat-Tu Le

Shared Pub. Internal Organizations

Houston Methodist Hospital

Organizational unit: Schools & Hospitals

5

Center for Bioenergetics

Organizational unit: Programs

1

Department of Cardiology

Organizational unit: Departments

1

Department of Medicine

Organizational unit: Departments

1
has Research OutputsResearch Output by Nhat-Tu Le

Shared Pub. External Organizations

University of Rochester Medical Center

External organization: Academic

11

University of Texas M. D. Anderson Cancer Center

External organization: Unknown

6

Department of Cardiovascular Sciences, Houston Methodist Research Institute,

External organization: Academic

3

Department of Cardiology, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Unit 1101, 1515 Holcombe Blvd., Houston, Texas, 77030-4009, USA. nle3@mdanderson.org.

External organization: Unknown

2

Department of Cardiology - Research, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: jabe@mdanderson.org.

External organization: Unknown

2
has Research OutputsResearch Output by Nhat-Tu Le

Shared Pub. Internal co-authors

has co-authored Research OutputsResearch Output with Nhat-Tu Le

Shared Pub. External co-authors

Jun ichi Abe

External person

25

Keigi Fujiwara

External person

20

Kyung-Sun Heo

External person

11

Eugene Chang

External person

8

Chang-Hoon Woo

External person

7
has co-authored Research OutputsResearch Output with Nhat-Tu Le

ID: 32959173