(410) 706-6240 (office)
Education and Training
Ph.D. in Pathophysiology, Southern Medical University, Guangzhou, China.
Studied the role of large-conductance Ca2+ activated K+ channel (BKCa) in hemorrhagic shock-induced vascular hyporeactivity.
Postdoc in Physiology, University of Tennessee Health Science Center, Memphis, TN.
Studied the physiological regulation of cerebral artery by ion channels and Ca2+ signaling proteins (BKCa, IP3R, TRPC).
Dr. Guiling Zhao’s research is focused on investigating the cellular and molecular mechanisms under which cardiovascular function is regulated by calcium, calcium related proteins and ion channels. She has discovered that type 1 IP3R (inositol trisphosphate receptor) is dominant in cerebral artery smooth muscle cells and that it regulates the vasoconstriction and dilatation, not only through calcium release from SR (sarcoplasmic reticulum), but also through crosstalk with plasma membrane ion channels (i.e. BKCa, TRPC3). Dr. Zhao also discovered that STIM1 (stromal interaction molecule 1), a calcium sensitive protein located in SR, regulates SERCA (Sarco/endoplasmic reticulum Ca2+ ATPase) activity in the steady state and the rate of SR Ca2+ leak in ventricular myocytes.
Taking advantage of her vascular biology background and being driven by her interest in cardiovascular physiology, Dr. Zhao’s current work centers on the regulation of blood flow control under microcirculation in the heart, using the unique working models and tools she has developed. She has found that ATP-sensitive K+ Channels (KATP) in cardiac myocyte drive the local blood flow through Electro-Metabolic signaling. Her ultimate goal is to make a mechanistic contribution and support in the development of new strategies to treat cardiovascular diseases.
Cardiovascular Disease, Physiology, Blood Pressure, Calcium Signaling, Calcium Spark, IP3Rs, STIM1, BKCa, Microcirculation, Blood flow control, Arterial smooth muscle cell, Ventricular Myocyte, Endothelial Cell, Cerebral Artery, Coronary Artery, Mesenteric Artery, Electrophysiology, Super Resolution Imaging, Confocal Imaging, Patch Clamp, Pressurized artery, Capillary, Pericyte, Electro-Metabolic Signaling
Zhao G*, Joca HC, Nelson MT*, Lederer WJ* (2020). ATP- and voltage-dependent electro-metabolic signaling regulates blood flow in heart. Proc Natl Acad Sci U S A. 2020 Mar 31;117(13):7461-7470. PMID:32170008 (*Corresponding author. See commentary "Metabolic-electrical control of coronary blood flow" by Grainger and Santana. Proc Natl Acad Sci U S A. 2020, 117(15):8231-8233. Editor's choice by Science).
Zhao G, Kaplan A, Greiser M, Lederer WJ (2020). The surprising complexity of KATP channel biology and of genetic diseases. J Clin Invest. 130(3):1112-1115. PMID:32065592
Boyman L, Coleman AK, Zhao G, Wescott AP, Joca HC, Greiser BM, Karbowski M, Ward CW, Lederer WJ (2019). Dynamics of the mitochondrial permeability transition pore: Transient and permanent opening events. Arch Biochem Biophys. 666:31-39. PMID: 30930285
Lin Q, Zhao G, Fang X, Peng X, Tang H, Wang H, Jing R, Liu J, Lederer WJ, Chen J, and Ouyang K (2016). IP3 receptors regulate vascular smooth muscle contractility and hypertension. JCI Insight. 1(17):e89402. PMCID: PMC5070959
Zemen BG, Lai MH, Whitt JP, Khan Z, Zhao G, and Meredith AL (2015). Generation of Kcnma1fl-tdTomato, a conditional deletion of the BK Channel a Subunit in mouse, Physiological Reports. 3(11):e12612. PMCID: PMC4673641
Zhao G, Li TY, Brochet DXP, Rosenberg P and Lederer WJ (2015). STIM1 enhances SR Ca2+ content through binding phospholamban in rat ventricular myocytes. Proc Natl Acad Sci U S A. 112 (34): E4792-801(Editor’s choice by Science Signaling). PMCID: PMC4553828
Zhang H, Sun AY, Kim JJ, Graham V, Nepliouev I, Finch EA, Zhao G, Li TY, Lederer WJ, Stiber JA, Pitt GS, Bursac N and Rosenberg PB (2015). STIM1-Ca2+ signaling modulates automaticity of the mouse sinoatrial node. Proc Natl Acad Sci U S A. 112(41):E5618-27. PMCID: PMC4611639
Lin L, Zhao L, Gao N, Yin R, Li S, Sun H, Zhou L, Zhao G, Purcell SW, Zhao J (2020). From multi-target anticoagulants to DOACs, and intrinsic coagulation factor inhibitors. Blood Rev. 39:100615 (Review). PMID:31492462
Lederer WJ, Hagen B, Zhao G (2012). Superresolution subspace signaling. Science. 336 (6081): 597-601. PMCID: PMC4235996
Zhao G*, Neeb ZP*, Leo MD, Pachuau J, Adebiyi A, Ouyang K, Chen J, and Jaggar JH (2010). Type 1 IP3 receptors activate BKCachannels via local molecular coupling in arterial smooth muscle cells. J Gen Physiol. 36(3):283-91 (* equal contribution). Journal of General Physiology Journal Club Article by Mujica and González. Selected for Journal of General Physiology Facebook Discussion. PMCID: PMC2931145
Adebiyi A, Zhao G, Narayanan D, Thomas CM, Bannister J, and Jaggar JH (2010). Isoform-selective physical coupling of TRPC3 channels to IP3 receptors in smooth muscle cells regulates arterial contractility. Circ Res. 106 (10):1603-12. PMCID: PMC3050672
Xi Q, Umstot E, Zhao G, Narayanan D, Leffler CW, and Jaggar JH (2010). Glutamate regulates Ca2+ signals in smooth muscle cells of newborn piglet brain slice arterioles through astrocyte- and heme oxygenase-dependent mechanisms. Am J Physiol Heart Circ Physiol. 298(2): H562-9. PMCID: PMC2822590
Bannister JP, Adebiyi A, Zhao G, Narayanan D, Thomas CM, Feng J, and Jaggar JH (2009). Alpha2delta-1 controls arterial diameter through acute and chronic regulation of smooth muscle cell CaV1.2 a1 subunits. Circ Res. 105: 948-955. PMID: 19797702
Zhao G, Adebiyi A, Blaskova E, Xi Q, and Jaggar JH (2008). Type 1 inositol 1,4,5-trisphosphate receptors mediate UTP-induced cation currents, Ca2+ signals, and vasoconstriction in cerebral arteries. Am J Physiol Cell Physiol. 295(5):C1376-84. PMCID: PMC2585000
Xi Q, Adebiyi A, Zhao G, Chapman KE, Waters CM, Hassid A, and Jaggar JH (2008). IP3 constricts cerebral arteries via IP3 receptor-mediated TRPC3 channel activation and independently of sarcoplasmic reticulum Ca2+ release. Circ Res. 102: 1118-1126. PMCID: PMC2430658
Zhao G, Zhao Y, Pan B, Liu J, Huang X, Zhang X, Cao C, Hou N, Wu C, Zhao KS, and Cheng H (2007). Hypersensitivity of BKCa to Ca2+ Sparks underlies vascular hyporeactivity in arterial smooth muscle. Circ Res. 101(5): 493-502. PMID: 17641230
Zhao G, Adebiyi A, Xi Q, and Jaggar, JH (2007). Hypoxia reduces KCa channel activity by inducing Ca2+ spark uncoupling in cerebral artery smooth muscle cells. Am J Physiol Cell Physiol. 292(6):C2122-8. PMCID: PMC2241735
Adebiyi A, Zhao G, Cheranov SY, Ahmed A, and Jaggar, JH (2007). Caveolin-1 abolishment attenuates the myogenic response in murine cerebral arteries. Am J Physiol Heart Circ Physiol. 292(3):H1584-92. PMCID: PMC2241733
Pan BX, Zhao GL, Huang XL, Zhao KS (2004). Calcium mobilization is required for peroxynitrite-mediated enhancement of spontaneous transient outward currents in arteriolar smooth muscle cells. Free Radical Biology & Medicine. 37(6):823-838. PMID: 15384203
Pan BX, Zhao GL, Huang XL, Zhao KS (2004). Mobilization of intracellular calcium by peroxynitrite in arteriolar smooth muscle cells from rats. Redox Report. 9(1): 49-55. PMID: 15035827
Pan BX, Zhao GL, Huang XL, Jin JQ, Zhao KS (2004). Peroxynitrite induces arteriolar smooth muscle cells membrane hyperpolarization with arteriolar hyporeactivity in rats. Life Sciences. 74 (10): 1199-1210. PMID: 14697404
Wang SH, Wei C, Zhao G, Brochet DXP, Shen J, Song LS, Wang W, Yang D and Cheng H (2004). Imaging Microdomain Ca2+ in muscle cell. Circ Res. 94(8):1011-22 (review). PMID: 15117829
Zhao KS, Huang X, Liu J, Huang Q, Jin C, Jiang Y, Jin J, Zhao G (2002). New approach to treatment of shock--restitution of vasoreactivity. Shock. 18(2):189-92. PMID: 12166785
Zhao Y, Wu ZH, Zhao GL (2006). Isolation and physiological characterization of mesenteric arterial smooth muscle cells. Nan Fang Yi Ke Da Xue Xue Bao (J South Med Univ). 26 (7):954-8. PMID: 16864085
Jin JQ, Zhao KS, Zhao GL, Huang XL, Pan BX (2004). Effect of SOD and NaHCO3 on the vascular hyporeactivity of rats after severe hemorrhagic shock. Di Yi Jun Yi Da Xue Xue Bao (J First Mil Med Univ). 24 (2):144-7. PMID: 14965811
Zhao GL, Pan BX, Huang XL, Zhao KS (2003). Properties of large-conductance calcium-activated potassium channel in rat mesenteric arteriole smooth muscle cells. Di Yi Jun Yi Da Xue Xue Bao (J First Mil Med Univ). 23(8):786-90. PMID: 12919898
Zhao GL, Pan BX, Huang XL, Jin J and Zhao KS (2003). Role of large conductance calcium-activated potassium channel of arteriolar smooth muscle cells in cell membrane hyperpolarization after severe hemorrhagic shock. Chin J Traumatol. 19(6): 329-332.
Zhang J, Huang Q, Liu Y, Huang X, Zhao G, Pan B, Kan W, Zhao K (2003). Effect of complex dribbing-pill of xue shuan tong on thrombus formation and microcirculation in rat. Zhong Yao Cai. 26 (12):881-2. PMID: 15058210
Zhao GL, Zhao KS (2002). Effect of Ca2+- activated K+ channel on regulation of myocyte tone in vascular smooth muscle. Chin J Traumatol. 18 (6): 382-384 (review).
Huang X, Jin J, Liu J, Zhao G, Huang Q, and Zhao K (2002). A study on therapeutic effect of glybenclamide and tiron recovering vasoreactivity in severe hemorrhagic shock rats. Chin J Traumatol. 18 (10): 620-623.
Zhao GL and Xu S (1998). Effects of Sodium Alginate Sulfates on haemorhological properties and platelet aggregation. Natural product Research and Development. 10(2):56-61.
Xu S, Zhao G, Zeng Z, Zheng G (1998). Effects of sodium alginate sulfates on antithrombosis and anticoagulant activity. Trop Oceanol (Redai Haiyang). 17 (2):32-37.
We are interested in the cardiovascular physiology, with an emphasis on Ca2+ signaling and its regulation in heart and vasculature. Specifically, the PI and her research team have been working on the following three projects:
STIM1 in heart.
As a SR Ca2+ sensing protein, STIM1 is well known as a stimulator of store-operated Ca2+ channel (SOCC) or Ca2+ release activated Ca2+ channel (CRAC), especially in non-excitable cells. However, the role of STIM1 in heart is not well understood. Using confocal, immunochemistry, patch clamp, and viral transfection techniques, we found that STIM1 in rat ventricular myocytes is not sensitive to SR Ca2+ depletion. Instead, STIM1 overexpression causes SR Ca2+ overload and cell arrhythmia. Further study indicates that STIM1 binds to phospholamban, an endogenous SERCA regulator and thus releases and activates SERCA. See Zhao et al (2015). PNAS.
Stretch-dependent Ca2+ signaling in arterial smooth muscle.
Using the new device developed in our lab, we were able to stretch single cardiac myocytes, skeletal muscle cells, as well as arterial smooth muscle cells. And cell length, cell tension, and Ca2+ signal are able to be recorded at the same time. The combination of the state-of-the-art techniques (single cell stretch, patch clamp, Ca2+ imaging) allows us to better understand the mechanisms of how pressure (stretch)-induced vasoconstriction occurs.
Blood flow control in heart.
One key question for us to ask is how heart blood flow is controlled by cardiomyocytes? Or how does heart communicate with arterioles? With this question, we have built a new ex vivo working model which enables us to image cardiac myocytes, capillary bed and coronary arteriole in the right ventricle papillary muscle at different pressures. Combining with our state-of-the-art optical imaging system, we were able to monitor the "blood flow" ex vivo as well as to image the diameter change of capillaries and arterioles. In addition, the function of cardiac pericytes is being investigated using this ex vivo working model.
July 2010 - June 2014: National Scientist Development Grant
Biochemistry, electrophysiology, imaging system, single cell stretch, and pressurizing artery enable us to investigate the function and the regulation of the muscle from single ion channel level to integrated tissue level.