515-271-7849 (Office Phone)
Areas of Expertise
|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 cardiovascular pathobiology and therapeutics, in particular disorders associated with menopause, heart failure and hypertension. A primary focus is on the regulation and therapeutic targeting of a number of G Protein-Coupled Receptors (GPCRs) that are involved in these conditions. We use a combination of molecular, biochemical and cellular approaches coupled with animal studies to investigate the mechanisms of action and therapeutic potential for these receptors. Current areas of emphasis include:
- Role of estrogen in cardiovascular pressor responses: Tissue responses through vasopressor receptors and adrenergic receptors play essential roles in the physiology and pathophysiology of the cardiovascular system. The increases in the risk and incidence of cardiovascular morbidity following menopause are attributed to the decline in circulating estrogen and are associated with abnormal adrenergic responses. Hormone replacement therapy (HRT), however, has not brought about the desired effects. Fine-tuning HRT unavoidably requires more in-depth understanding of the modes of actions of the different receptors for estrogen. A current focus in my laboratory is to understand the roles of these receptors, in particular the new G protein-coupled estrogen receptor 1 (GPER/GPR30) in the regulation of vasopressor responses in the cardiovascular system.
- Role of calmodulin (CaM) in the regulation of GPCR functions: CaM is the ubiquitous transducer of cellular Ca2+ signals and is estimated to interact with 300 cellular proteins. The expression of CaM, however, is insufficient for its targets, rendering CaM a limiting factor in all cardiovascular tissues. CaM has been shown to interact with a number of GPCRs; however, the roles of CaM in the many aspects of GPCR functions are still largely unknown. We recently introduced a new approach using biosensors to exhaustively identify CaM-binding domains in GPCRs and quantitatively characterize interaction properties. Using this approach, we have identified multiple locations for interaction with CaM with drastically different interaction properties and functional impacts on a number of GPCRs. Studies are underway to explore the roles of CaM in different aspects of GPCR functions, from regulation of agonist responses, trafficking as well as GPCR interactions with other partners.
- Regulation of cardiovascular Ca2+ signaling by GPER/GPR30: The dynamics of Ca2+ signaling in the cells of the blood vessel wall play a critical role in controlling vascular functions. Estrogen affects many Ca2+-dependent processes in the cardiovascular system; however, its effects and associated mechanisms of actions on components of the Ca2+ signaling machinery are largely unknown. We have recently found direct interaction and mutual functional impact between the new G protein-coupled estrogen receptor 1 (GPER/GPR30) and the plasma membrane Ca2+-ATPase4b, a major Ca2+ extrusion mechanism in the vasculature. Further studies are underway to examine the influence of this new receptor on other key molecular switchers of the Ca2+ signaling machinery. These studies will provide useful information to exploit this novel receptor therapeutically.
These studies are supported by the National Institutes of Health and the Iowa Osteopathic and Educational Research Funds.
- Whitcomb V, Wauson E, Christian D, Clayton S, Giles J, Tran QK*. Regulation of Beta Adrenoceptor-mediated Myocardial Contraction and Calcium Dynamics by the G Protein-coupled Estrogen Receptor 1. Biochem Pharmacol. 2019 Nov. 21:113727. Doi: 10.1016/j.bcp.2019.113727. *Corresponding author.
- Black DJ, Tran QK, Keightley A, Chinawalkar A, McMullin C, Persechini A. Evaluating Calmodulin-Protein Interactions by Rapid Photoactivated Cross-Linking in Live Cells Metabolically Labeled with Photo-Methionine. J. Proteome Res. 2019 Oct 4;18(10):3780-3791. doi: 10.1021/acs.jproteome.9b00510. Epub 2019 Sep 20.
- Gebert-Oberle B, Giles J, Clayton S, Tran QK*. Calcium/calmodulin regulates signaling at the alpha1A adrenoceptor. Eur J Pharmacol. 2019 Apr 5;848:70-79. doi: 10.1016/j.ejphar.2019.01.042. Epub 2019 Jan 25. *Corresponding author.
- Ehlers K, Clements R, VerMeer M, Giles J, Tran QK*. Novel regulations of the angiotensin II receptor type 1 by calmodulin. Biochem Pharmacol 2018 Jun;152:187-200. doi: 10.1016/j.bcp.2018.03.027. Epub 2018 Mar 30. *Corresponding author.
- Terry LE, VerMeer M, Giles J, Tran QK*. Suppression of store-operated Ca2+ entry by activation of GPER: contribution to a clamping effect on endothelial Ca2+ signaling. Biochem J. 2017 Oct 23;474(21):3627-3642. doi: 10.1042/BCJ20170630. *Corresponding author.
- Watanabe H, Tran QK. Targeting the NO-sGC-cGMP pathway in Pulmonary Arterial Hypertension. (Book Chapter) in: Diagnosis and Management of Pulmonary Arterial Hypertension – From Bench to Bedside. Springer 2017. ISBN: 978-981-287-840-3 (eBook); 978-981-287-839-7 (Hardcover)
- Tran QK*, Firkins RM, Giles J, Francis S, Matnishian V, Tran P, VerMeer M, Jasurda JS, Burgard MA, Gebert-Oberle B. Estrogen Enhances Linkage in the Vascular Endothelial Calmodulin Network via a Feedforward Mechanism at the G Protein-Coupled Estrogen Receptor 1. J. Biol. Chem. 2016 May 13;291(20):10805-23. doi: 10.1074/jbc.M115.697334. *Corresponding author.
- Tran QK*, VerMeer M, Burgard MA, Hassan AB, Giles J. Hetero-oligomeric complex between the G protein-coupled estrogen receptor 1 and the plasma membrane Ca2+-ATPase 4b. (2015) J Biol Chem 2015 May 22;290(21):13293-307. doi: 10.1074/jbc.M114.628743. *Corresponding author.
- Arnett DC, Persechini A, Tran QK, Black DJ, Johnson CK. FEBS Lett. 2015 Apr 11. pii: S0014-5793(15)00237-9. doi: 10.1016/j.febslet.2015.03.035. Fluorescence quenching studies of structure and dynamics in calmodulin-eNOS complexes.
- Odagiri K, Inui N, Miyakawa S, Hakamata A, Wei J, Takehara Y, Sakahara H, Sugiyama M, Alley M, Tran QK, Watanabe H. Abnormal Hemodynamics in the Pulmonary Artery Depicted with Time-resolved 3D Phase Contrast Magnetic Resonance Imaging (4D-Flow) in a Young Patient with Idiopathic Pulmonary Arterial Hypertension. Circ J 2014; 78(7): 1770-1772.
- 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. “State of the Nation: How can the US ensure its medical research and healthcare does not fall behind on the global stage?” Research Roundtable Group Interview, International Innovation, US Focus Issue, Jul. 2013, 21 – 23.
- Tran QK. The GPER Effect. International Innovation, US Focus Issue, Jul. 2013, 88.
- Tran QK. Renewed hope for HRT users. International Innovation, US Focus Issue, Jul. 2013, 89-90.
- 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 Chem2009;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, Watanabe H. Calcium signaling in the endothelium. Handb Exp Pharmacol. 2006(176 Pt.1)145-87.
- 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.
- Tran QK, Watanabe H. Myosin Light Chain Kinase in Endothelial Cell Calcium Signaling and Endothelial Functions. (Book Chapter) In: Atherosclerosis, Hypertension and Diabetes (Book series: Progress in Experimental Cardiology. Vol. 8, pp 163-174; 2003). Eds. Pierce G.N., Nagano M, Zahradka P, and Dhalla NS. Kluwer Academic/Plenum Publishers. ISBN 1-4020-7311-9.
- 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, Ohashi K, Watanabe H. Calcium signaling in endothelial cells. Cardiovasc Res 2000;48(1);13-22
- 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.
2018 – Distinguished Scholar Award, Des Moines University
2012 – 2015 – Academic Enhancement Research Award, National Institutes of Health, NHLBI
2012 – President, Iowa Physiological Chapter, American Physiological Society
2012 – Excellence in Scholarship Award, Des Moines University
2001 – International Research Exchange 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
Email Kim Tran