University of Surrey

Faculty of Health and Medical Sciences

Research FHMS Blood Cells : Anna Tanczos Paramedics FHMS

Professor Jian-Mei Li

Professor of Cardiovascular Biology

Image of Jian-Mei Li
Image of Jian-Mei Li

Qualifications:MBBS (ShanXi Medical University, China), MD(Geneva University, Switzerland), PhD (King.s College London, UK)

Email:
Phone: Work: 01483 68 6475
Room no: 12 AY 02

Further information

Research Interests

Redox-signalling through NADPH oxidase

 

Cardiovascular cells such as cardiac myocytes, smooth muscle cells, endothelial cells and fibroblasts express constitutively a multi-subunit NADPH oxidase, which appears to be an important source of O2- generation in these cells. Under physiological condition, the activity of this oxidase is very low and the small amount of O2- thus generated has been suggested to modulate redox-sensitive intracellular signalling pathways to maintain normal cellular function. However, the activity of this enzyme can be up-regulated by agonists such as protein kinase C activators (PMA), cytokines (TNF-a), growth factors (EGF) and angiotensin II. Enhanced oxidant signalling through NADPH oxidase is involved in the development of atherosclerosis, hypertension and cardiac hypertrophy. We are in the process of investigating the mechanisms involved in the regulation of NADPH oxidase signalling in cardiovascular cells using molecular approaches including site-directed mutagenesis, gene knockout and over-expression and the state of the art techniques of microarray and proteinomics.

Reactive oxygen species signalling in endothelial cell cycle regulation

Endothelial cell growth, death and function are important determinants of vascular homeostasis related to many diseases such as atherosclerosis, diabetes, and are also involved in ageing. Very recently, it has been discovered that endothelial cell function and cell fate (as well as in other cardiovascular cells) are tightly coupled to the cellular redox state. Controlled endogenous reactive oxygen species (ROS) generation is absolutely necessary for normal vascular cell proliferation, angiogenesis and remodelling. However, excessive ROS production causes abnormal vascular cell cycling, and even death. We aim to identify the precise upstream and downstream signalling pathways linked to NADPH oxidase and its product (ROS) in the regulation of cell cycle control in endothelial cells.

The role of reactive oxygen species and NADPH oxidase in the development of endothelial dysfunction and in the pathogenesis of atherosclerosis, hypertension and diabetes

Endothelial dysfunction characterized by increased ROS production (oxidative stress) occurs in the early stage of atherosclerosis, hypertension and diabetes. Recent research has revealed that a multicomponent NADPH oxidase constitutively expressed in endothelial cells is a major source of ROS production and the activation of this enzyme contributes to endothelial dysfunction. This research programme includes human studies, in vivo transgenic models, ex vivo organ studies and in vitro cell culture. We are investigating the role of ROS and the NADPH oxidase in the pathophysiology of these diseases. In the mean time we are trying to identify the molecules that are regulated by ROS.

Adenosine receptor regulation of NADPH oxidase activity

Adenosine, a metabolite of ATP abundantly produced in the cardiovascular system, has important effects on endothelial function. Adenosine has 4 receptor subtypes. Among them, the A2A receptor is the predominant form expressed in endothelium and is involved in mediating microvascular dilation. Our recent work has discovered an important role of adenosine through its receptors in the regulation of NADPH oxidase activity in the cardiovascular system. We are using multiple approaches to investigate the mechanism and signalling pathways that link the activity of adenosine receptors to the levels of ROS production in endothelial cells. We aim to discover new drug and to develop better therapeutic strategies for oxidative stress related cardiovascular diseases.

Publications

    1. Fan L., L. Teng, and J-M. Li. Knockout of p47phox uncovers a critical role of p40phox in reactive oxygen species production in microvascular endothelial cells. Arterioscler. Thromb. Vasc. Biol. 2009; 29 [Epub ahead of print] See Paper Dio:10.1161/ATVBAHA.109.191502.
    2. Fan L., D. Sawbridge, V. George, L. Teng, A. Bailey, I. Kitchen, and  J-M, Li. Chronic cocaine induced Cardiac oxidative stress and MAPK activation: The role of Nox 2 oxidase. J. Pharmacol. Exp. There. 2009.328: 99-106.
    3. Ribe D., D. Sawbridge, S. Thakur, M. Hussey, C. Ledent, I. Kitcken, S. Hourani, J-M. Li . Adenosine A2A receptor signalling regulation of cardiac NADPH oxidase activity. Free. Rad. Biol. Med. 2008; 44:1433-1442.
    4. Duncan E., S. Walker, V. Ezzat, S. Wheatcroft, J-M. Li , A. Shah, M. Kearney. Accelerated endothelial dysfunction in mild pre-diabetic insulin resistance: the early role of reactive oxygen species. Am. J. Physiol. Endoc. & Metab. 2007; 293:E1131-1139.
    5. Li J-M., L.M. Fan, V. T. George, G. Brooks. Nox2 regulates endothelial cell cycle arrest and apoptosis via p21cip1 and p53. Free. Rad. Biol. Med. 2007; 43: 976-986.
    6. Li J-M., L.M. Fan, M.R. Christie, A. Shah. Acute TNFα signaling via NADPH oxidase in microvascular endothelial cells: Role of p47phox phosphorylation and binding to TRAF4. Mol. Cell. Biology 2005; 25:2320-2330.
    7. Noronha, B.T., J-M. Li , S.B. Wheatcroft, A.M. Shah, M.T. Kearney. Inducible nitric oxide synthase has divergent effects on vascular and metabolic function in obesity. Diabetes. 2005; 54:1082-1089.
    8. Li J-M., and A.M. Shah. Endothelial cell superoxide generation: regulation and relevance for cardiovascular pathophysiology (Invited Review). Am. J Physiol. Regulatory, Integrative and Comparative Physiology. 2004; 287:R1014-R1030.
    9. Wheatcroft S.B., A.M. Shah, J-M. Li , E. Duncan, B.T. Noronha, P.A. Crossey, M.T. Kearney. Preserved glucoregulation but attenuation of the vascular actions of insulin in mice heterozygous for knockout of the insulin receptor. Diabetes. 2004; 53:2645-2652.
    10. Li J-M., S. B. Wheatcroft, L. M. Fan, M. T. Kearney and A. M. Shah. Opposing roles of p47phox in basal versus angiotensin II-stimulated alterations in vascular O2.- production, vascular tone and mitogen-activated protein kinase activation. Circulation. 2004; 109:1307-1313.
    11. Li J-M., L. M. Fan, A. Shah and G. Brooks. Targeting αvβ3 and α5β1 for gene delivery to proliferating VSMC. synergistic effect of TGF-β1. Am. J. Physiol. Heart Circ. Physiol. 2003;285:H1123-H1131
    12. Byrne, J.A., D. J. Grieve, J. K. Bendall, J-M. Li , C. Gove, J.D. Lambeth, A.C. Cave, and A.M. Shah. Contrasting Role of NADPH oxidase isoform in pressure-overload versus angiotensin II-induced cardiac hypertrophy. Circ. Res. 2003;93:802-804.
    13. Li, J-M., and A.M.Shah. Mechanism of endothelial cell NADPH oxidase activation by angiotensin II: Role of the p47phox subunit. J. Biol. Chem. 2003; 278:12094-12100.
    14. Li, J-M., and A.M.Shah. ROS generation by non-phagocytic NADPH oxidase: Potential relevance in diabetic nephropathy. J. Am. Soc. Nephrol. 2003;14: S221-S226.
    15. Li, J-M. A.M. Mullen, S. Yun, F. Wientjes, G. Brouns, A.J. Thrasher, J. Rose and A.M. Shah. Essential role of the NADPH oxidase subunit p47phox in endothelial cell superoxide production in response to phorbol ester and tumor necrosis factor-α. Circ. Res. 2002;90:143-150.
    16. Li, J-M. and A.M. Shah. Intracellular localization and preassembly of the NADPH oxidase complex in cultured endothelial cells. J. Biol. Chem. 2002; 277:19952-19960.
    17. Li, J-M., N. P. Gall, D. J. Grieve, M. Y. Chen, and A.M. Shah. Activation of myocardial NADPH oxidase and mitogen activated protein kinases during progression of pressure overload cardiac hypertrophy to failure. Hypertension 2002;40:504-510.
    18. Layland, J., J-M. Li , and A.M. Shah. Role of cyclic GMP-dependent protein kinase in the contractile response to exogenous nitric oxide in isolated cardiac myocytes. J. Physiol. 2002; 540.2:457-467.
    19. Li, J-M. A.M. Mullen, and A.M. Shah. Phenotypic properties and characteristics of superoxide production by mouse coronary microvascular endothelial cells. J. Mol. Cell. Cardiol. 2001;33:1119-1131.
    20. Li, J-M. and A.M. Shah. Differential NADPH- versus NADH-driven superoxide production by phagocyte-type endothelial cell NADPH oxidase. Cardiovasc. Res. 2001; 52:477-486.
    21. Tavernier, B., J-M. Li , M. M. El-Omar, S. Lanone, Z-K. Yang, I. P. Trayer, A. Mebazaa and A. M. Shah. Cardiac contractile impairment associated with increased phosphorylation of troponin I in endotoxemic rats. FASEB J. 2001; 15:294-296.

Teaching

Pathology and Medicine BMS2008

Practical Physiology BMS1009

Practical Biochemistry and Immunology BMS2002

Peripheral Pharmacology BMS3037

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