Identification of mechanisms underlying atrial fibrillation and effective therapies

Dr X Wang
Dr Vicky Liu
Applications accepted all year round
Self-Funded PhD Students Only

Faculty of Biology, Medicine and Health, University of Manchester

About This PhD Project

Project Description
Funding Notes
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References

Project Description

Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice with particular high prevalence in aged populations. To understand the mechanisms underlying the development of AF is crucial for developing effective therapy for AF. As part of electrical remodeling, gap junction remodeling leading to electrical perturbation favours the recurrence or perpetuation of AF. However, the underlying signalling mechanism is largely unknown. Using tissue specific conditional knockout technique, we have established a number of atrium-specific knockout mouse models in which the components of the MAP kinases are specifically deleted in atrial cardiomyocytes. The aim of this project is to determine the role of MAP kinase signalling pathway in atria and in relation to atrial arrhythmogenesis. Novel mathematical models will be generated in this project as tools to determine the key aetiological factor in atrial fibrillation, and to identify molecular targets for the treatment of AF.

This project will provide a comprehensive training for a PhD student in a wealth of molecular and cellular approaches, in vivo cardiac functional study on genetically modified mice, electrophysiology and computational simulation methods.

Funding Notes

This project has a Band 2 fee. Details of our different fee bands can be found on our website (View Website). For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (View Website).

Informal enquiries may be made directly to the primary supervisor.

References

Liu W, Zi M, Naumann R, Ulm S, Jin J, Taglieri DM, Prehar S, Gui J, Xiao R, Neyses L, Soralo RJ, Ke Y, Cartwright EJ, Lei M, Wang X. Pak1 is a novel signaling regulator attenuating cardiac hypertrophy in mice. Circulation. 2011;124(24):2702-2715.

Liu W, Zi M, Chi H., Jin J, Prehar S, Neyses L, Cartwright EJ, Flavell RA, Davis RJ, Wang X. Deprivation of MKK7 in cardiomyocytes provokes heart failure in mice when exposed to pressure overload. J Mol Cell Cardiol. 2011;50 (4):702-711.

Kimura TE, Jin JW, Zi M, Prehar S, Liu W, Oceandy D, Abe JI, Neyses L, Weston AH, Cartwright EJ, Wang X. Targeted Deletion of the Extracellular Signal-Regulated Protein Kinase 5 Attenuates Hypertrophic Response, and Promotes Pressure Overload-Induced Apoptosis in the Heart. Circ Res. 2010;106:961-970.

Liu W, Zi M, Jin JW, Prehar S, Oceandy D, Kimura TE, Lei M, Neyses L, Weston AH, Cartwright EJ, Wang X. Cardiac-Specific Deletion of Mkk4 Reveals Its Role in Pathological Hypertrophic Remodeling, but Not in Physiological Cardiac Growth. Circ Res. 2009;104:904-914.

Zi M, Kimura TE, Liu W, Jin J, Higham J, Kharche S, Hao G, Shi Y, Shen W, Prehar S, Mironov A, Neyses L, Bierhuizen MFA, Boyett MR, Zhang H, Cartwright EJ, Lei M, Wang X. MKK4 deficiency in cardiomyocytes causes connexin 43 remodeling and couples hypertrophic signals to ventricular arrhythmogenesis. J Biol Chem. 2011;286:17821-17830.

Wang, X. (2009) Cre transgenic mouse lines. In Transgenesis, 3rd Edition. Editor: Elizabeth J. Cartwright. Methods Mol Biol. 561, 265-273.

Cartwright, E.J. and Wang, X. (2009) Transgenesis. Molecular Biology and Biotechnology. Editor: JM Walker and R Rapley. 5th Edition, 1-10.

Egom E, Mohamed T, Mamas M, Shi Y, Liu W, Chirico D, Stringer S, Ke Y, Shaheen M, Wang T, Chacko S, Wang X, Solaro S, Fath-Ordoubadi F, Cartwright E, Lei M. Activation of Pak1/Akt/eNOS signaling following sphingosine-1-phosphate release as part of amechanism protecting cardiomyocytes against ischemic cell injury. Am J Phyiology. 2011;301(4):H1487-H1495.

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Identification of mechanisms underlying atrial fibrillation and effective therapies

University of Manchester

Faculty of Biology, Medicine and Health

Manchester