A. ?Personal Statement

My long-standing research focuses on exploring the mechanisms underlying the regulation of cardiac excitation - contraction (EC) coupling regulating mechanisms, including exploring new regulation genes and epigenetic regulatory mechanism of the expression of ion channel subunits in normal heart and ion channel remodeling in diseased heart, and the study of the novel mechanism and treatment of cardiac hypertrophy and heart failure. I have served as the dean for the department of pathophysiology, Shenzhen University School of Medicine ?since 2009. Research in my lab has been continuously supported by 4 regular grants of the National Natural Science Foundation in China (NSFC) and 4 grants of Basic Research Foundation of Shenzhen since 2009. I have published more than 40 papers in the peer-reviewed professional journals just as Cell, Circ Res, Cardiovasc Res, J Mol Cell Cardiol, Free Radical Biology & Medcine. I have mentored 7 PhD candidates and 10 MSc candidates in all.

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B. ?Positions and Honors

Positions and Employment

09/89 – 07/91 ???????? Teaching assistant, Third Military Medical University; Chongqing, China

09/95 – 04/09 ???????? Lecturer, Associate professor, Professor, First Military Medical University (Southern

Medical University); Guangzhou, China

04/09 –present ????? Professor, Shenzhen University School of Medicine, Shenzhen, Guangdong, China

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C. ?Publications (*: corresponding/co-corresponding author)

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Our research fall in the regulation mechanisms of ion channels, calcium signaling, and cardiac function in normal heart, and structural and functional remodeling in diseased heart, using many kinds of methods including advanced molecular biology methods, confocal microscopic imaging, and patch clamp technique and animal model of heart failure, so that to fundamentally enrich our understanding in cardiac EC coupling regulation mechanism and provide new targets and therapeutic strategies for heart disease.

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1.????? Yang J, Zhang R, Jiang X, Lv J, Li Y, Ye H, Liu W, Wang G, Zhang C, Zheng N, Dong M, Wang Y, Chen P, Santosh K, Jiang Y*, Liu J*. Toll-like receptor 4 induced ryanodine receptor 2 oxidation and sarcoplasmic reticulum Ca²⁺ leakage promote cardiac contractile dysfunction in sepsis. J Biol Chem. 2018 Jan 19;293(3):794-807.

2.????? Zhang C, Chen B, Wang Y, Guo A, Tang Y, Khataei T, Shi Y, Kutschke WJ, Zimmerman K, Weiss RM, Liu J, Benson CJ, Hong J, Ma J, Song LS. MG53 is dispensable for T-tubule maturation but critical for maintaining T-tubule integrity following cardiac stress. J Mol Cell Cardiol. 2017 Nov;112:123-130.

3.????? Liu W, Chen P, Deng J, Lv J, Liu J*. Resveratrol and polydatin as modulators of Ca²⁺ mobilization in the cardiovascular system. Ann N Y Acad Sci. 2017 Sep; 1403(1):82-91.

4.????? Dong M, Zheng N, Ren LJ, Zhou H, Liu J*. Increased expression of STIM1/Orai1 in platelets of stroke patients predictive of poor outcomes. Eur J Neurol. 2017 Jul;24(7):912-919.

5.????? Dong M, Liao S, Chen Y, Zheng N, Ma J, Xiao Z, Li Y, Ding W, Liu J. Trans-Polydatin protects the mouse heart against ischemia/reperfusion injury via inhibition of the renin-angiotensin system (RAS) and Rho kinase (ROCK) activity. Food Funct. 2017 Jun 21;8(6):2309-2321.

6.????? Tang H, Wang H, Lin Q, Fan F, Zhang F, Peng X, Fang X, Liu J, Ouyang K. Loss of IP3 Receptor-Mediated Ca²⁺ Release in Mouse B Cells Results in Abnormal B Cell Development and Function. J Immunol. 2017 Jul 15;199(2):570-580.

7.????? Lin Q, Zhao G, Fang X, Peng X, Tang H, Wang H, Jing R, Liu J, Lederer WJ, Chen J, Ouyang K. IP3 receptors regulate vascular smooth muscle contractility and hypertension. JCI Insight. 2016 Oct 20;1(17):e89402.

8. Liu WJ, Deng JX, Wang G, Gao KP, Lin ZX, Liu SY, Wang YH, Liu J*. Manipulation of KCNE2 expression modulates action potential duration, and Ito and IK in rat and mouse ventricular myocytes. Am J Physiol Heart Circ Physiol. 2015; 309(8):H1288-302

9. Dong M, Ding W, Liao Y, Liu Y, Yan D, Zhang Y, Wang R, Zheng N, Liu S, ?Liu J*. Polydatin prevents hypertrophy in phenylephrine induced neonatal mouse cardiomyocytes and pressure-overload mouse models. Eur J Pharmacol. 2015;746:186-97

10. Yan D, Luo X, Li Y, Liu W, Deng J, Zheng N, Gao K, Huang Q, Liu J*. Effects of Advanced Glycation End Products on Calcium Handling in Cardiomyocytes. Cardiology 2014; 129(2):75-83

11. Ding W, Dong M, Deng J, Yan D, Liu Y, Xu T, Liu J*. Polydatin attenuates cardiac hypertrophy through modulation of cardiac Ca2+ handling and calcineurin-NFAT signaling pathway. Am J Physiol Heart Circ Physiol. 2014 Sep 1; 307(5):H792-802.

12. Liu W, Deng J, Wang G, Zhang C, Luo X, Yan D, Su Q, Liu J*. KCNE2 modulates cardiac L-type Ca2+ channel. J Mol Cell Cardiol. 2014 Jul; 72:208-18.

13. Zhang C, Mo M, Ding W, Liu W, Yan D, Deng J, Luo X, Liu J*. High-mobility group box 1 (HMGB1) impaired cardiac excitation-contraction coupling by enhancing the sarcoplasmic reticulum (SR) Ca2+ leak through TLR4-ROS signaling in cardiomyocytes. J Mol Cell Cardiol. 2014 September; 74: 260–273.

14. Zhang W, Li K, Zhu X, Wu D, Shang W, Yuan X, Huang Z, Zheng M, Wang X, Yang D, Liu J*, Cheng H. Subsarcolemmal Mitochondrial Flashes Induced by Hypochlorite Stimulation in Cardiac Myocytes. Free Radic Res. 2014 Sep; 48(9):1085-94.

15. Jiang X, Liu W, Deng J, Lan L, Xue X, Zhang C, Cai G, Luo X, Liu J*. Polydatin protects cardiac function against burn injury by inhibiting sarcoplasmic reticulum Ca2+ leak by reducing oxidative modification of ryanodine receptors. Free Radic Biol Med 2013; 60: 292-9.

16. Ma X, Du J, Zhang P, Deng J, Liu J, Lam FF, Li RA, Huang Y, Jin J, Yao X. Functional Role of TRPV4-KCa2.3 Signaling in Vascular Endothelial Cells in Normal and Streptozotocin-Induced Diabetic Rats. Hypertension. 2013；62: 134 – 139.

17.Deng JX, Liu WJ, Wang YR, Dong M, Zheng M, Liu J*. Polydatin modulates Ca2+ handling, excitation-contraction coupling and b-adrenergic signaling in rat ventricular myocytes. J Mol Cell Cardiol, 2012; 53(5): 646-656.

18.Yang C, Mo X, Lv J, Liu X, Yuan M, Dong M, Li L, Luo X, Fan X, Jin Z, Liu Z, Liu J*. Lipopolysaccharide enhances FcRI-mediated mast cell degranulation by increasing Ca2+ entry through store-operated Ca2+ channels: implications for LPS exacerbating allergic asthma. Exp Physiol, 2012; 97(12): 1315 - 1327.

19.Yuan M, Li J, Lv J, Mo X, Yang C, Chen X, Liu Z, ?Liu J*. Polydatin (PD) inhibits IgE-mediated passive cutaneous anaphylaxis in mice by stabilizing mast cells through modulating Ca(2+) mobilization. Toxicol Appl Pharmacol, 2012; 264(3)：462-469.

20.Kaitao Li, Wanrui Zhang, Huaqiang Fang, Wenjun Xie, Jie Liu, Ming Zheng, Xianhua Wang, Wang Wang, Wenchang Tan, Heping Cheng. Superoxide Flashes Reveal Novel Properties of Mitochondrial Reactive Oxygen Species Excitability in Cardiomyocytes. Biophysic J, 2012, 102(5): 1011–1021.

22.He ML, Liu WJ, Sun HY, Wu W, Liu J, Tse HF, Lau CP, Li GR. Effects of ion channels on proliferation in cultured human cardiac fibroblasts. J Mol Cell Cardiol, Aug 2011; 51(2): 198-206.

23.Chen JB, Liu WJ, Che H, Liu J, Sun HY, Li GR. Adenosine-5'-triphosphate Up-regulates Proliferation in Cultured Human Cardiac Fibroblasts. Br J Pharmacol. 2012 Jun;166(3): 1140-50.

24.Luo X, Deng J, Liu N, Zhang C, Huang Q, Liu J*. Cellular mechanism underlying burn serum- generated bidirectional regulation of excitation-contraction coupling in isolated rat cardiomyocytes. Shock, 2011; 35(4): 388-95.

25.Liu W, Deng J, Xu J, Wang H, Yuan M, Liu N, Jiang Y, Liu J*. High-mobility group box 1 (HMGB1) downregulates cardiac transient outward potassium current (Ito) through downregulation of Kv4.2 and Kv4.3 channel transcripts and proteins. J Mol Cell Cardiol, Sep 2010; 49(3): 438-48.

26.Wang G, Zhu X, Xie W, Han P, Li K, Sun Z, Wang Y, Chen C, Song R, Cao C, Zhang J, Wu C, Liu ?J*, Cheng H. Rad As a Novel Regulator of Excitation–Contraction Coupling and ?-Adrenergic Signaling in Heart. Circ Res 2010 Feb 5;106(2):317-27.

27.Wang W, Fang H, Groom L, Cheng A, Zhang W, Liu J, Wang X, L i K, Han P, Zheng M, Yin J, Wang W, Mattson MP, Kao JPY, Lakatta1 EG., Sheu S-S, Ouyang K, Chen J, Dirksen RT, Cheng H. Superoxide Flashes in Single Mitochondria. Cell 2008 Jul 25;134(2):279-90.

28.Yan Y, Liu J*, Wei C, Li K, Xie W, Wang Y, Cheng H*. Bidirectional Regulation of Ca2+ Sparks by

Mitochondria-Derived ROS in Cardiac Myocytes. Cardiovasc Res, 2008; 77(2): 432-441.

29.Deng J, Wang G, Huang Q, Yan Y, Li, Tan W, Jin C, Wang Y, ?Liu J*. Oxidative Stress Induced Leaky Sarcoplasmic Reticulum Underlying Acute Heart Failure in Severe Burn Trauma. Free Radical Biology & Medicine. 2008; 44(3): 375-385.

30. Liu W, Wang H, Chen W, Deng J, Jiang Y, Liu J*. Co-expression of KCNE2 and KChIP2c modulates the electrophysiological properties of Kv4.2 current in COS-7 cells. Acta Pharmacologica Sinica 2008; 29(6):653-660.

31. Zhao G, Zhao Y, Pan B, Liu J, Huang X, Zhang X, Cao C, Hou N, Wu C, Zhao K, Cheng H. Hypersensitivity of BK_Ca to Ca^2＋ Sparks Underlies Hyporeactivity of Arterial Smooth Muscle in Shock. Circ Res. 2007;101:493-502.

32. Tseng GN, Sonawane KD, Zhang M, Liu J, Guy HR. Probing the outer mouth structure of the hERG channel with peptide toxin footprinting and molecular modeling. Biophys J. 2007; 92: 2524-2540.

33. Jiang M, Zhang M, Maslennikov IV, Liu J, Wu DM, Korolkova YV, Arseniev AS, Grishin EV, Tseng GN. Dynamic conformational changes of extracellular S5-P linkers in the hERG channel. J Physiol 2005；569(Pt 1):75-89.

34. Zhang M, Liu J, Tseng GN. Gating Charges in the Activation and Inactivation Processes of the hERG Channel. J Gen Physiol 2004; 124: 703 - 718.

35. Jiang M, Zhang M, Tang D, Clemo H, Liu J, Holwitt D, Kasirajan V, Pond AL, Wettwer E, Tseng GN. KCNE2 protein is expressed in ventricles of different species, and changes in its expression contribnute to electrical remodeling in diseased hearts. Circ 2004; 109: 1783-1788.

36. Liu J, Zhang M, Jiang M, Tseng G-N. Negative charges in the transmembrane domains of the HERG K channel are involved in the activation and deactivation gating processes. J Gen Physiol 2003;121(6): 599-614.

37. Liu J, Zhang M, Jiang M, Tseng G-N. Structural and functional role of the extracellular S5-P linker in the HERG potassium channel. J Gen Physiol 2002; 120(5): 723-737.

38. Pardo-Lopez L, Zhang M, Liu J, Jiang M, Possani LD, and Tseng G-N. Mapping the binding site of an HERG-specific peptide toxin (ErgTx) to the channel's outer vestibule. J Biol Chem 2002;277:16403-16411.

39. Zhao K, Huang X, Liu J, Huang Q, Jin C, Jiang Y, Jin J, Zhao G. New approach to treatment of shock-? ?restitution of vasoreactivity. Shock 2002; 18(2): 189-192.

40. Zhao K, Liu J, Yang G, Jin C, Huang Q, Huang X. Peroxynitrite leads to arteriolar smooth muscle cell? ?membrane? hyperpolarization and low vasoreactivity in severe shock.? Clinical Hemorheology and?Microcirculation 2000; 23: 259-267.D. ?Research Support

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Ongoing Research Support

NSFC (China) project (31671179) ? 01/01/2017 to 12/31/2020

Jie Liu, PI ￥610,000 (direct cost)

Investigation of the role and the underlying mechanisms of HDAC inhibition in the treatment of downregulation of KChIP2 expression and Ito activity in cardiac hypertrophy

Shenzhen Science and Technology Innovation Commission grant (JCYJ20160308091147262)? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ?07/01/2017 to 12/30/2018

Jie Liu, PI ?????????????????????????????????????????????????????????????????????????????????? ￥500,000

Mechanistic investigation of HIMF in the development of cardiac hypertrophy

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Completed Research Support

NSFC(China) project (31371159) ?? 01/01/2014 to 12/31/2017

Jie Liu, PI ￥860,000

The mechanisms underlying MG53 regulation of the expression of cardiac auxilliary subunit KChIP2 and the

role of which in the heart electricity steady state regulation

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NSFC(China) project (31171096) ?? 01/01/2012 to 12/31/2015

Jie Liu, PI ￥650,000

The molecular mechanisms underlying KCNE2 regulation of L-type Ca2+ channels and the physiological and pathological significance

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NSFC(China) project (30973122) ?? 01/01/2010 to 12/31/2012

Jie Liu, PI ￥380,000

The abnormal regulation of FKBP12.6 on RyR2 contributes to sarcoplasmic reticulum Ca2+ leak in burn generated cardiomyopathy

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NSFC(China) project (30570418) ?? 01/01/2006 to 12/31/2008

Jie Liu, PI ￥270,000

Exploration of the regulation of KCNE2 on Kv channels and the mechanisms for LQT6

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NSFC(China) project (30570418) ?? 01/01/2000 to 12/31/2002

Jie Liu, PI ￥140,000

Exploration of the mechanisms underlying shear stress-induced eNOS expression

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