
David X. Zhang, PhD
Associate Professor
Locations
- Pharmacology and Toxicology
Contact Information
General Interests
Education
Research Interests
The overall emphasis of our laboratory is to understand signaling mechanisms in regulation of blood vessel reactivity and homeostasis under normal states as well as in diseases such as coronary artery disease (CAD), hypertension, and diabetes.
This regulation involves two major cell types in the vessel wall, namely the endothelial and smooth muscle cells. The endothelium is a single layer of cells lining the lumen of blood vessels. It regulates vascular tone and homeostasis through the release of various vasoactive factors. In response to either mechanical (e.g., flow or shear stress) or chemical (e.g., receptor agonists) cues, the endothelium synthesizes and releases nitric oxide (NO), prostacyclin (PGI2), and less well-understood endothelium-derived hyperpolarizing (EDH) factors such as metabolites of arachidonic acid and hydrogen peroxide (H2O2). These endothelial factors can diffuse out of the endothelial layer into the medial layer of the vessel wall and in turn regulate many functions of smooth muscle cells, including smooth muscle resting tone, relaxation and contraction response, and cell proliferation. In human coronary arterioles, H2O2 serves as a key flow-elicited vasodilator factor in the presence of CAD whereas other traditional factors (NO and PGI2) play a more significant role in vasodilation in the absence of CAD or its risk factors. Although both H2O2 and NO dilate coronary arterioles, each mediator has different or opposing non-vasomotor effects on vascular homeostasis and propensity for atherosclerosis. It remains largely unsolved how flow elicits two distinct classes of vasodilators in subjects with CAD versus those without. In addition, whether and how vascular smooth muscle of the human microcirculation changes function during CAD and other diseases remains poorly understood.
The current research is focused on the role of transient receptor potential (TRP) channels, a newly recognized family of calcium-permeable cation channels expressed in vascular endothelial cells, in mediating the conversion of vasodilator factors (NO/PGI2 in health and H2O2 in disease) in human coronary microcirculation. A second line of research relates to the function of smooth muscle K+ channels, such as Ca2+-activated K+ (KCa) and voltage-gated K+ (KV) channels, in arterioles from subjects with and without CAD. These smooth muscle K+ channels are the key end-effector of vasomotor control in the microcirculation. The studies are biomedically significant because they involve the use of human tissue in addition to animal models. Studies are performed with an integrated approach ranging from cellular and molecular techniques (Ca2+ imaging, protein mutagenesis), electrophysiology (patch clamping), to isolated vessel reactivity and in vivo vascular function assays.
Publications
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(Zhang DX, Gutterman DD.) Arterioscler Thromb Vasc Biol. 2019 12;39(12):2454-2456 PMID: 31770031 PMCID: PMC6980742 SCOPUS ID: 2-s2.0-85075688768 11/27/2019
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TRPV4 regulates matrix stiffness and TGFβ1-induced epithelial-mesenchymal transition.
(Sharma S, Goswami R, Zhang DX, Rahaman SO.) J Cell Mol Med. 2019 02;23(2):761-774 PMID: 30450767 PMCID: PMC6349341 SCOPUS ID: 2-s2.0-85056765656 11/20/2018
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(Palygin O, Miller BS, Nishijima Y, Zhang DX, Staruschenko A, Sorokin A.) FASEB J. 2019 02;33(2):2636-2645 PMID: 30303741 PMCID: PMC6338658 SCOPUS ID: 2-s2.0-85061064863 10/12/2018
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(Cao S, Anishkin A, Zinkevich NS, Nishijima Y, Korishettar A, Wang Z, Fang J, Wilcox DA, Zhang DX.) J Biol Chem. 2018 04 06;293(14):5307-5322 PMID: 29462784 PMCID: PMC5892583 SCOPUS ID: 2-s2.0-85045077479 02/21/2018
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(Nishijima Y, Korishettar A, Chabowski DS, Cao S, Zheng X, Gutterman DD, Zhang DX.) Microcirculation. 2018 01;25(1) PMID: 29161755 PMCID: PMC5760438 SCOPUS ID: 2-s2.0-85040240704 11/22/2017
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TRPV4 ion channel is a novel regulator of dermal myofibroblast differentiation.
(Sharma S, Goswami R, Merth M, Cohen J, Lei KY, Zhang DX, Rahaman SO.) Am J Physiol Cell Physiol. 2017 May 01;312(5):C562-C572 PMID: 28249987 PMCID: PMC6105932 SCOPUS ID: 2-s2.0-85018753321 03/03/2017
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TRPV4 ION Channel Is Associated with Scleroderma.
(Goswami R, Cohen J, Sharma S, Zhang DX, Lafyatis R, Bhawan J, Rahaman SO.) J Invest Dermatol. 2017 04;137(4):962-965 PMID: 27889423 SCOPUS ID: 2-s2.0-85015888580 11/28/2016
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(Nishijima Y, Cao S, Chabowski DS, Korishettar A, Ge A, Zheng X, Sparapani R, Gutterman DD, Zhang DX.) Circ Res. 2017 Feb 17;120(4):658-669 PMID: 27872049 PMCID: PMC5315616 SCOPUS ID: 2-s2.0-85000399498 11/23/2016
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(Gebremedhin D, Zhang DX, Weihrauch D, Uche NN, Harder DR.) PLoS One. 2017;12(5):e0176796 PMID: 28472069 PMCID: PMC5417564 SCOPUS ID: 2-s2.0-85019077900 05/05/2017
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(Gebremedhin D, Zhang DX, Carver KA, Rau N, Rarick KR, Roman RJ, Harder DR.) Prostaglandins Other Lipid Mediat. 2016 07;124:16-26 PMID: 27174801 PMCID: PMC5287377 SCOPUS ID: 2-s2.0-84973896991 05/14/2016
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A novel TRPV4-specific agonist inhibits monocyte adhesion and atherosclerosis.
(Xu S, Liu B, Yin M, Koroleva M, Mastrangelo M, Ture S, Morrell CN, Zhang DX, Fisher EA, Jin ZG.) Oncotarget. 2016 Jun 21;7(25):37622-37635 PMID: 27191895 PMCID: PMC5122337 SCOPUS ID: 2-s2.0-84978176831 10/23/2016
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(Baumgardt SL, Paterson M, Leucker TM, Fang J, Zhang DX, Bosnjak ZJ, Warltier DC, Kersten JR, Ge ZD.) Circ Heart Fail. 2016 Jan;9(1):e002424 PMID: 26763290 PMCID: PMC4714787 SCOPUS ID: 2-s2.0-84955258675 01/15/2016