Associate professor - Physiology and Pharmacology
Associate professor - Master of Science in Biomedical Sciences
Associate professor - Doctor of Osteopathic Medicine
|Education||Postdoctoral Training, University of Missouri-Kansas City|
Ph.D. in Medical Sciences, Hamamatsu University School of Medicine, Japan
Advanced Training in Clinical Cardiology, Hamamatsu University Hospital, Japan
Residency, Internal Medicine & Cardiology, HCMC University Hospitals
M.D., University of Medicine and Pharmacy at HoChiMinh City, Vietnam
My laboratory is interested in various aspects of vascular biology, in particular vascular disorders associated with menopause, diabetes and hypertension. Calmodulin is the most important transducer of intracellular Ca2+ signals by virtue of its requirement for the functions of numerous cellular proteins and its insufficient expression for all its targets. Modulating aspects of calmodulin-dependent signaling thus represents therapeutic potential for many cardiovascular disorders. We use a combination of molecular, cellular and biochemical approaches coupled with multi-wavelength intracellular imaging techniques to investigate the mechanisms and therapeutic options for alterations in calmodulin-dependent signaling associated with menopause, diabetes and hypertension. Currently we are focusing on two main areas:
- Regulation of GPER-mediated signaling in the vasculature by calmodulin: Despite the clear linkage between postmenopause and cardiovascular disease, hormone replacement therapy has not proven to be cardioprotective. The novel G protein-coupled estrogen receptor 1 (GPER, or GPR30) has been implicated in a vast array of cardiovascular functions, cancer, bone development, brain functions, and reproductive functions. Studies in this project aim at identifying GPER as a novel calmodulin-binding protein and test the overall hypothesis that GPER activation triggers in the vasculature feed-forward mechanisms that involve calmodulin both at the receptor level and downstream effectors, linking signaling pathways mediated by different estrogen receptors. The role of GPER in intracellular Ca2+ signaling and cell-cell interaction via modulation of calmodulin-dependent activities are also being examined. We are developing novel biosensors that allow studies of specific interactions between GPER and other binding partners. We expect that these studies will provide timely information that help form the basis for targeting estrogen receptor subtypes for preventive and therapeutic purposes. More information on this project can be found in the July 2013 (US Focus) issue (pp. 88-91) of International Innovation (http://www.research-europe.com/magazine/HEALTHCARE2/RR4/index.html).
- Intercellular interactions in the control of vascular functions: Vascular endothelial cells and smooth muscle cells are two principal cell types of vascular tissue. Interactions between these two cell types are essential in the coordinated regulation of vascular functions. We are investigating paracrine and autocrine mechanisms of intercellular interactions in the vasculature via calmodulin-dependent activities through which endothelial and smooth muscle cell functions are coordinated. Novel models of primary vascular cells for intercellular studies and intracellular imaging, coupled with other molecular and biochemical approaches are employed. These studies are expected to reveal novel mechanisms governing intercellular interactions in physiological processes such as angiogenesis and vasculogenesis, and disease states associated with endothelial regeneration following vascular injuries.
These studies are currently supported by the National Institutes of Health (HL112184) and the Iowa Osteopathic and Educational Research Funds (IOER-R&G).
- Tran QK*, VerMeer M. Biosensor-based approach identifies four distinct calmodulin-binding domains in the G Protein-coupled Estrogen Receptor 1. PLOS ONE 2014; 9(2): e89669.doi:10.1371/journal.pone.0089669. *Corresponding author.
- Tran QK*, Watanabe H. Novel oral prostacyclin analog with thromboxane synthase inhibitory activity for management of pulmonary arterial hypertension. Circ J. 2013; 77 (8), 1994-5. *Corresponding author.
- Persechini A, Tran QK, Black DJ, Gogol EP. Calmodulin facilitates electron transfer in endothelial nitric oxide synthase by positioning the reductase domains near the oxygenase domains. FEBS Letters 2013; 587:297-301.
- Tran QK*, Newton A, Smith K, Stumbo T, Mortensen L., Plundo D. An Interdisciplinary Learning Opportunity Affecting Attitudes in Interprofessional Care. Med. Sci. Ed. 2013; 23(3S) 482 – 493. *Corresponding author.
- Tran QK, Leonard J, Black DJ, Persechini A. Effects of combined phosphorylation at Ser-617 and Ser-1179 in endothelial nitric oxide synthase on EC50(Ca2+) values for calmodulin binding and enzyme activation. J. Biol Chem 2009;284(18):11892-9.
- Tran QK, Leonard J, Black DJ, Persechini A. Phosphorylation within an Autoinhibitory Domain in Endothelial Nitric Oxide Synthase Reduces the Ca2+ Concentrations Required for Calmodulin To Bind and Activate the Enzyme. Biochemistry 2008;47(28):7557-66.
- Tran QK, Black DJ, Persechini A. Dominant affectors in the calmodulin network shape the time courses of target responses in the cell. Cell Calcium 2005;37(6):541-553.
- Black DJ, Tran QK, Persechini A. Monitoring the total available calmodulin concentration in intact cells over the physiological range in free Ca2+. Cell Calcium 2004; 35(5):415-25
- Takeuchi K, Watanabe H, Tran QK, Ozeki M, Sumi D, Hayashi T, Iguchi A, Ignarro LJ, Ohashi K, Hayashi H. Nitric oxide: inhibitory effects on endothelial cell calcium signaling, prostaglandin I2 production and nitric oxide synthase expression. Cardiovasc Res 2004;62:194-201.
- Tran QK, Black DJ, Persechini A. Intracellular coupling via limiting calmodulin. J. Biol. Chem. 2003;278(27):24247-50.
- Takeuchi K, Watanabe H, Tran QK, Ozeki M, Uehara A, Katoh H, Satoh H, Terada H, Hayashi H. Effects of cytochrome P450 inhibitors on agonist-induced Ca2+ responses and production of NO and PGI2 in vascular endothelial cells. Mol Cell Biochem. 2003;248(1-2):129-34.
- Watanabe H, Ohashi K, Takeuchi K, Yamashita K, Yokoyama T, Tran QK, Satoh H, Terada H, Ohashi H, Hayashi H. Sildenafil for primary and secondary pulmonary hypertension. Clin Pharmacol Ther. 2002;71(5):398-402.
- Tran QK, Watanabe H, Le H-Y, Takeuchi K, Hattori Y, Tomioka H, Ohashi K, Hayashi H. Insulin inhibits coronary endothelial cell Ca2+ entry and coronary artery relaxation. J Cardiovas Pharmacol 2001; 38 (6):885-892.
- Tran QK, Watanabe H, Le H-Y, Ling P, Seto M, Takeuchi K, Ohashi K. Myosin light chain kinase regulates capacitative Ca2+ entry in human monocytes/macrophages. Arterioscler Thromb Vasc Biol 2001;21; 509-515.
- Watanabe H, Tran QK, Takeuchi K, Fukao M, Liu MY, Kanno M, Hayashi T, Iguchi A, Seto M, Ohashi K. Myosin light-chain kinase regulates endothelial Ca2+ entry and endothelium-derived vasodilation. FASEB J. 2001; 15(2):282-284.
- Tomioka H, Hattori Y, Fukao M, Watanabe H, Akaishi Y, Sato A, Tran QK, Sakuma I, Kitabatake A, Kanno M. Role of endothelial Ni2+-sensitive Ca2+ entry pathway in regulation of EDHF in porcine coronary artery. Am J Physiol Heart Circ Physiol 2001; 280:H730-H737.
- Tran QK, Watanabe H, Le H-Y, Yang J, Takeuchi K, Kadomatsu K, Muramatsu T, Ohashi K. Midkine inhibits bradykinin-induced endothelial Ca2+ signaling and nitric oxide production. Biochem Biophys Res Commun. 2000; 276;830-836.
- Tran QK, Watanabe H, Zhang XX, Takahashi R, Ohno R. Involvement of myosin light chain kinase in chloride-sensitive Ca2+ influx in porcine aortic endothelial cells. Cardiovasc Res. 1999;44:623-631.
- Watanabe H, Takahashi R, Tran QK, Takeuchi K, Kosuge K, Satoh H, Uehara A, Terada H, Hayashi H, Ohno R, Ohashi K. Increased cytosolic Ca2+ concentration in endothelial cells by calmodulin antagonists. Biochem Biophys Res Commun. 1999;265:697-702.
- Fukao M, Hattori H, Sato A, Liu MY, Watanabe H, Tran QK, Kanno M. Relationship between NaF- and thapsigargin-induced endothelium-dependent hyperpolarization in rat mesenteric artery. Brit J Pharmacol. 1999;126:1567-1574.
Awards and honors
2012-2014 - Academic Enhancement Research Award, National Institutes of Health
2012 - Distinguished Scholar Award, Des Moines University
2001 - International Exchange Travel Award (Shizuoka, Japan)
1997-2001 - Fellow of the Ministry of Education, Culture and Science of Japan
1996-1997 - Fellow of the Asian Youth Fellowship Program, Japanese Government