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Mechanisms of oxidative stress and Nox-signalling in cardiovascular diseases related to insulin-resistance and diabetes

  • Full or part time
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

Metabolic disorders such as obesity, insulin resistance and type-II diabetes are primary risk factors for the development of cardiovascular diseases. Recently, oxidative stress due to the activation of NADPH oxidase (Nox) has been found to play a key role in the pathogenesis of metabolic disorder-related cardiovascular diseases such as hypertension and atherosclerosis. The Nox family has at least 7 members (Nox 1-5, Duox 1-2). However, it remains unclear about the role of individual Nox enzyme and their signalling pathways in mediating metabolic disorders and cardiovascular dysfunction. Therefore, the overall aim of this PhD research project is to investigate the mechanisms and the signalling pathways of these Noxes in the pathogenesis of insulin-resistance, diabetes and cardiovascular diseases using animal model of human diseases of wild-type versus Nox2 knockout and Apo E knockout mice.

The student will attend the training course for in vivo work and will learn many in vivo skills and pathology of cardiovascular diseases. The student will have plenty opportunity to learn the biochemical and molecular techniques such as measurements of reactive oxygen species production in tissues and in cells, the Western blot; immunofluorescence, confocal microscopy, HPLC, and molecular techniques such as genotyping, quantitative real-time RT-PCR of gene expression. The student will also have plenty opportunities to present his/her research data at national and international conferences.

Funding Notes

Degree (at least 2:1 or a master degree) in biological/ medical sciences or related subject.
Experience in laboratory research.
Self-motivated and keen to learn


1. Fan, L.M., G. Douglas, J.K. Bendall, E. McNeill, M. J. Crabtree, A. B. Hale, A. Mai, J-M. Li, M. A. McAteer, J. E. Schneider, R. P. Choudhury, and K. M. Channon. Endothelial Cell-Specific ROS Production Increases Susceptibility to Aortic Dissection. Circulation. 2014;129:2661-2672.
2. Meijles D.N., L.M. Fan, B. J. Howlin, and J-M. Li. Molecular Insights of p47phox Phosphorylation Dynamics in the Regulation of NADPH Oxidase Activation and Superoxide Production. J. Biol. Chem. 2014; 289:22759-22770.
3. Du, J., L. M. Fan, A. Mai, and J-M. Li. Crucial roles of Nox2-derived oxidative stress in deteriorating insulin receptor and endothelial function in dietary obesity of mice after middle age. Br. J. Pharmacol. 2013;170:1064-1077.
4. Teng, L., L. M. Fan, D. Meijles, and J-M. Li. Divergent effects of p47phox phosphorylation at S303-4 or S379 on TNFα-signaling via TRAF4 and MAPK in endothelial cells. Arterioscler. Thromb. Vasc. Biol. 2012; 32:1488-1496.
5. 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.

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