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Investigating the link between chronic kidney disease and cardiovascular disease


Institute of Cardiovascular Sciences

Applications accepted all year round Self-Funded PhD Students Only

About the Project

Patients with chronic kidney disease are 40% more likely to develop cardiovascular disease, however, mechanisms driving the cardiovascular pathogenesis are unclear. We are offering an opportunity for an excellent candidate to apply for a 3 year PhD studentship examining the cellular basis of cardiovascular disease in patients with chronic kidney disease.

By having access to serum samples from a large, prospectively collected and followed cohort of kidney patients (1-3) this study will afford a unique opportunity to assess the biological impact of endogenous cardiotonic steroids on both organ and cellular cardiac function, and allow development of new biomarkers for chronic kidney disease and cardiovascular disease. Specifically, we propose to examine the role of intracellular sodium/calcium and cardiotonic steroids (4) in determining cardiac dysfunction using novel fluorescence techniques (5,6) and examine the steroidogenesis pathways. Using a translational approach, the PhD Student will utilise the full capabilities of the new Institute of Cardiovascular Sciences at the University of Birmingham. The impact of endogenous cardiotonic steroids on cardiovascular pathogenesis will be examined by a combination of liquid chromatography-mass spectrometry, novel fluorescence bioassays and use of human induced pluripotent stem cell-derived cardiomyocytes, within the laboratory of Dr Davor Pavlovic at the Institute of Cardiovascular Sciences and Prof Wiebke Arlt and Dr Angela Taylor at the Institute of Metabolism and Systems Research. The key outcomes of the PhD Studentship will be: 1. Development of analytical tools for detection and quantification of cardiotonic steroids; 2. A paper on the role of endogenous cardiotonic steroids in development of cardiovascular disease in patients with chronic kidney disease; 3. A paper on the steroid synthesis and conversion pathways.

Required equipment is available at the Institute of Cardiovascular Sciences and the Institute of Metabolism and Systems Research. The supervisory team provides a full translational approach, including basic science and the interface between these disciplines.

Applicants should have a commitment to cardiovascular research and have an interest in translational medicine (application of basic science skills to advance clinical practice). Applicants should preferably have some experience in analytical chemistry techniques (liquid chromatography-mass spectrometry), cellular and organ level cardiovascular methods, electrophysiology and molecular biology techniques. Applicants need to be able to work as part of a multidisciplinary research team.

For more information about the Pavlovic research group, the Institute of Cardiovascular Sciences, Institute of Metabolism and Systems Research and Birmingham Cardiorenal group please see :

http://www.birmingham.ac.uk/staff/profiles/cardiovascular-sciences/pavlovic-davor.aspx
http://www.birmingham.ac.uk/research/activity/cardiovascular-sciences/index.aspx
http://www.birmingham.ac.uk/research/activity/metabolism-systems/index.aspx
http://www.birmingham.ac.uk/research/activity/cardiovascular-sciences/research/bcrg/index.aspx


To apply, please submit your CV and a covering email/letter for consideration to Dr Davor Pavlovic.


Funding Notes

Applicants should indicate in their applications how they intend to fund their studies. We have a thriving community of international PhD students and encourage applications from students of any nationality able to fund their own studies (Government scholarship), or wish to apply for their own funding (e.g. China Scholarship Council, Commonwealth Studentships etc).

We would only consider applications from prospective students with:
- a good biomedical degree, with interests in any of the areas outlined above,
- good command of the English language,
- a source of funding to cover tuition fees and bench fees

References

1. Chue CD, Townend JN, Steeds RP, Ferro CJ. Evaluating the effects of sevelamer carbonate on cardiovascular structure and function in chronic renal impairment in birmingham: The crib-phos randomised controlled trial. Trials. 2011;12:30

2. Moody WE, Tomlinson LA, Ferro CJ, Steeds RP, Mark PB, Zehnder D, Tomson CR, Cockcroft JR, Wilkinson IB, Townend JN. Effect of a reduction in glomerular filtration rate after nephrectomy on arterial stiffness and central hemodynamics: Rationale and design of the earnest study. American heart journal. 2014;167:141-149 e142

3. Stringer S, Sharma P, Dutton M, Jesky M, Ng K, Kaur O, Chapple I, Dietrich T, Ferro C, Cockwell P. The natural history of, and risk factors for, progressive chronic kidney disease (ckd): The renal impairment in secondary care (riisc) study; rationale and protocol. BMC nephrology. 2013;14:95

4. Pavlovic D (2014) The role of cardiotonic steroids in the pathogenesis of cardiomyopathy in chronic kidney disease. Nephron Clinical Practice 128(1-2):11-21.
5. Pavlovic D, Hall A, Kenninton E, Fuller W, Despa S, Bers D and Shattock MJ (2013) Nitric oxide regulates cardiac intracellular Na+ and Ca2+ by modulating Na/K ATPase via PKC and phospholemman-dependent mechanism. Journal of Molecular and Cellular Cardiology Aug; 61:164-71

6. Mahmmoud YA, Shattock M, Cornelius F and Pavlovic D (2014) Inhibition of K transport through NaK-ATPase by Capsazepine: Role of membrane span 10 of the a-subunit in the modulation of ion gating. PLoS One. May 9;9(5):e96909.

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