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Professor Jian-Mei Li

Professor of Cardiovascular Biology

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

Journal articles

  • Teng L, Fan LM, Meijles D, Li JM. (2012) 'Divergent Effects of p47phox Phosphorylation at S303-4 or S379 on Tumor Necrosis Factor-α Signaling via TRAF4 and MAPK in Endothelial Cells.'. Arterioscler Thromb Vasc Biol, United States: 32 (6), pp. 1488-1496.
    doi: 10.1161/ATVBAHA.112.247775
  • Howlin BJ, Meijles DN, Li JM. (2012) 'Consensus in silico computational modelling of the p22phox subunit of the NADPH oxidase'. Elsevier Computational Biology and Chemistry, 39, pp. 6-13.
    doi: 10.1016/j.compbiolchem.2012.05.001
  • Cahill-Smith S, Li JM. (2011) 'THE ROLE OF OXIDATIVE STRESS IN THE DEVELOPMENT OF ENDOTHELIAL DYSFUNCTION AND HYPERTENSION IN AGEING'. HEART, 97 (24)
    doi: 10.1136/heartjnl-2011-301156.22
  • Du J, Li J-M. (2011) 'Knockout of p47(phox) Attenuates Angiotensin II-induced Endothelial Dysfunction and Vessel Damage in Vivo'. CIRCULATION, 124 (21)
  • Teng L, Li J-M. (2011) 'Double Serine Phosphorylation of P47(Phox) At 303-304 is Critical for Acute Tnf alpha-Induced Ros Production but Not for Mapk Activation in Endothelial Cells'. CIRCULATION, 124 (21)
  • Du J, Li J-M. (2011) 'A Crucial Role of Nox2 In Middle-Age Obese-Related Hyperglycaemia and Endothelial Dysfunction in Mice'. CIRCULATION, 124 (21)
  • Tickner J, Fan LM, Du J, Meijles D, Li J-M. (2011) 'Nox2-derived ROS in PPARγ signaling and cell-cycle progression of lung alveolar epithelial cells'. Free Radical Biology and Medicine, 51 (3), pp. 763-772.
    doi: 10.1016/j.freeradbiomed.2011.05.027
  • Thakur S, Du J, Hourani S, Ledent C, Li J-M. (2010) 'Inactivation of Adenosine A(2A) Receptor Attenuates Basal and Angiotensin II-induced ROS Production by Nox2 in Endothelial Cells'. AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC JOURNAL OF BIOLOGICAL CHEMISTRY, 285 (51), pp. 40104-40113.
    doi: 10.1074/jbc.M110.184606
    Full text is available at: http://epubs.surrey.ac.uk/205737/
  • Fan LM, Teng L, Li J-M. (2009) 'Knockout of p47(phox) Uncovers a Critical Role of p40(phox) in Reactive Oxygen Species Production in Microvascular Endothelial Cells'. LIPPINCOTT WILLIAMS & WILKINS ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 29 (10), pp. 1651-U609.
    doi: 10.1161/ATVBAHA.109.191502
  • Fan L, Sawbridge D, George V, Teng L, Bailey A, Kitchen I, Li J-M. (2009) 'Chronic Cocaine-Induced Cardiac Oxidative Stress and Mitogen-Activated Protein Kinase Activation: The Role of Nox2 Oxidase'. AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 328 (1), pp. 99-106.
    doi: 10.1124/jpet.108.145201
  • Ribe D, Sawbridge D, Thakur S, Hussey M, Ledent C, Kitchen I, Hourani S, Li J-M. (2008) 'Adenosine A(2A) receptor signaling regulation of cardiac NADPH oxidase activity'. ELSEVIER SCIENCE INC FREE RADICAL BIOLOGY AND MEDICINE, 44 (7), pp. 1433-1442.
    doi: 10.1016/j.freeradbiomed.2007.12.035
  • Duncan ER, Walker SJ, Ezzat VA, Wheatcroft SB, Li J-M, Shah AM, Kearney MT. (2007) 'Accelerated endothelial dysfunction in mild prediabetic insulin resistance: the early role of reactive oxygen species'. AMER PHYSIOLOGICAL SOC AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 293 (5), pp. E1311-E1319.
    doi: 10.1152/ajpendo.00299.2007
  • Li J-M, Fan LM, George VT, Brooks G. (2007) 'Nox2 regulates endothelial cell cycle arrest and apoptosis via p21 (cip1) and p53'. ELSEVIER SCIENCE INC FREE RADICAL BIOLOGY AND MEDICINE, 43 (6), pp. 976-986.
    doi: 10.1016/j.freeradbiomed.2007.06.001

Conference papers

  • Meijles DN, Howlin BJ, Li J-M. (2012) 'BIOINFORMATIC IMAGING AND MOLECULAR INVESTIGATION FOR A ROLE OF P22(PHOX) C242T POLYMORPHISM IN INHIBITING ENDOTHELIAL ROS PRODUCTION'. B M J PUBLISHING GROUP HEART, Manchester, ENGLAND: Annual Conference of the British-Cardiovascular-Society (BCS) 98, pp. A68-A69.
    doi: 10.1136/heartjnl-2012-301877b.121
  • Teng L, Li J-M. (2010) 'TRANSCRIPTIONAL REGULATION OF P40PHOX AND P47PHOX EXPRESSION VIA HBP1 IN ENDOTHELIAL CELLS'. B M J PUBLISHING GROUP HEART, Univ Oxford, Oxford, ENGLAND: Conference on Myocardial Energetics and Redox in Health and Disease 96 (4)
    doi: 10.1136/hrt.2009.191064k
  • Teng L, Li J-M. (2010) 'ROLES OF P47PHOX S303/S304 PHOSPHORYLATION IN TNF alpha-INDUCED ENDOTHELIAL REACTIVE OXYGEN SPECIES PRODUCTION AND MITOGEN-ACTIVATED PROTEIN KINASE ACTIVATION'. B M J PUBLISHING GROUP HEART, Univ Oxford, Oxford, ENGLAND: Conference on Myocardial Energetics and Redox in Health and Disease 96 (4)
    doi: 10.1136/hrt.2009.191049g
  • Thakur S, Hourani S, Li JM. (2009) 'REGULATION OF ANGIOTENSIN II-INDUCED ROS PRODUCTION AND REDOX-SIGNALLING BY THE ADENOSINE A2A RECEPTOR IN ENDOTHELIAL CELLS'. LIPPINCOTT WILLIAMS & WILKINS HYPERTENSION, Nice, FRANCE: 14th Annual Meeting of the European-Council-for-Cardiovascular-Research 54 (5), pp. 1165-1165.
  • Fan L, Sawbridge D, Bailey A, Li JM. (2009) 'THE ROLE OF OXIDATIVE STRESS IN MEDIATING COCAINE-INDUCED MAPK ACTIVATION AND CARDIAC MYOCYTE INJURIES'. LIPPINCOTT WILLIAMS & WILKINS HYPERTENSION, Nice, FRANCE: 14th Annual Meeting of the European-Council-for-Cardiovascular-Research 54 (5), pp. 1177-1177.
  • Fan LM, Vinoj G, Brooks G, Li JM. (2008) 'Nox2 modulation of cell cycle inhibitory protein p21cip1 in endothelial cells'. B M J PUBLISHING GROUP HEART, Manchester, ENGLAND: Annual Scientific Conference of the British-Cardiovascular-Society/British-Society-for-Cardiovascular-Research 94, pp. A43-A44.
  • Fan L, Sawbridge D, Bailey A, Kitchen I, Li J-M. (2008) 'The mechanism of chronic cocaine exposure on cardiac reactive oxygen species production and mitogen-activated protein kinase activation'. B M J PUBLISHING GROUP HEART, Manchester, ENGLAND: Annual Scientific Conference of the British-Cardiovascular-Society/British-Society-for-Cardiovascular-Research 94, pp. A115-A115.
  • Fan L, George V, Brooks G, Li J-M. (2008) 'Nox2 modulation of cell cycle inhibitory protein p21(cip1) expression in endothelial cells'. ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, Athens, GREECE: 28th Annual Meeting of the European Section of the International-Society-for-Heart-Research 44 (4), pp. 713-713.
    doi: 10.1016/j.yjmcc.2008.02.006
  • Fan L, Sawbridge D, Bailey A, Kitchen I, Li J-M. (2008) 'The role of NADPH oxidase in cocaine-induced cardiac oxidative stress and redox signalling'. ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, Athens, GREECE: 28th Annual Meeting of the European Section of the International-Society-for-Heart-Research 44 (4), pp. 713-713.
    doi: 10.1016/j.yjmcc.2008.02.007
  • Ribe D, Li J-M. (2007) 'Modulation of NADPH oxidase activity and redox signalling by the adenosine A2A receptor antagonist SCH58261'. B M J PUBLISHING GROUP HEART, Univ Reading, Reading, ENGLAND: Spring Meeting of the British-Society-for-Cardiovascular-Research 93 (11)
  • George VT, Li J-M. (2007) 'The role of reactive oxygen species and NADPH oxidase in endothelial cell cycle regulation'. B M J PUBLISHING GROUP HEART, Univ Reading, Reading, ENGLAND: Spring Meeting of the British-Society-for-Cardiovascular-Research 93 (11)
  • Fan LM, George V, Brooks G, Li J-M. (2007) 'Nox2 signalling via p21(Cip1) and p53 in endothelial cell cycle regulation'. LIPPINCOTT WILLIAMS & WILKINS CIRCULATION, Orlando, FL: 80th Annual Scientific Session of the American-Heart-Association 116 (16), pp. 300-301.
  • Duncan E, Walker SJ, Ezzat V, Wheatcroft S, Li J-M, Shah A, Keamey M. (2006) 'Mild whole body insulin resistance and accelerated endothelial dysfunction: Increased reactive oxygen species derived from mitochondria during ageing despite preserved glycaemic control'. LIPPINCOTT WILLIAMS & WILKINS CIRCULATION, Chicago, IL: 79th Annual Scientific Session of the American-Heart-Association 114 (18), pp. 107-107.

Teaching

Pathology and Medicine BMS2046

Practical Physiology BMS1032

Clinical Immunology BMS3054