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About the Project
Research interests/description of main research theme:
Fibrosis is a hard to treat condition of major socioeconomic importance, with ~45% of all deaths in the developed world being attributed to some type of chronic fibro-proliferative disease and is exemplified by heart disease. Cardiac fibrosis is highly predictive of hospitalization and mortality. Patients diagnosed with dilated or non-ischemic cardio-myopathy concurrent with cardiac fibrosis are 18x more likely to die from cardiovascular disease than those without fibrosis. This is because cardiac fibrosis translates into impaired heart pumping, reduced myocardial electrical transmission and increased arrhythmia, often leading to heart failure and sudden cardiac death.
As a therapeutic target, the need to tackle fibrosis is well-recognized internationally but the mechanisms driving cardiac fibrosis are unclear. Our work is focused on development of multi-cellular cardiac fibrosis models[1] and identification of novel anti-fibrotic targets[2]. Our work has recently highlighted reduced reversibility of fibrosis when fibroblasts are chronically activated in vitro. Whether this is the case in vivo needs investigation.
We will utilise a combination of in vitro cardiac fibrosis models, in vivo work and in silico modelling studies to examine the mechanisms driving the cardiac fibrosis. Our expertise in cardiac optical mapping will be used to assess mechanisms driving fibrosis-mediated electrical dysfunction and arrhythmias[3-8].
Project Aims
Our work has recently highlighted reduced reversibility of fibrosis when fibroblasts are chronically activated in vitro [9]. Whether this is the case in vivo needs investigation.
Research Environment and Learning Outcomes: Required equipment is available at the Institute of Cardiovascular Sciences. Dr Pavlovic has an excellent track record in supervising postgraduate students to completion and acts as Deputy Director for Postgraduate Studies at the College of Medical and Dental Sciences. He has published over 55 papers. Dr Pavlovic leads a team of 1 postdoctoral researcher and 4 PhD students. He also acts as Editor in Chief of JMCC Plus [link] and is a Council member of the European Section of the International Society for Heart Research [link].
Person Specification
Applicants should have a commitment to cardiovascular research and have an interest in translational medicine (application of discovery science skills to advance clinical practice). Applicants should preferably have some experience in 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 please see:
http://www.birmingham.ac.uk/staff/profiles/cardiovascular-sciences/pavlovic-davor.aspx
https://www.birmingham.ac.uk/research/cardiovascular-sciences/cardiac-diseases
To apply, please submit your CV and a covering email/letter for consideration to Dr Davor Pavlovic (d.pavlovic@bham.ac.uk).
Applicants will need to submit the following documentation during the application process.
· Detailed CV, including your nationality and country of birth;
· Covering letter highlighting your research experience/capabilities and why you wish to undertake a PhD in the team;
· Names and addresses of two referees;
· Copies of your degree certificates with transcripts written in English;
· Evidence of your proficiency in the English language, if applicable.
· Evidence of scholarship application/funding or independent funding.
Additional Information
University of Birmingham offers pre-sessional English Language courses through the Birmingham International Academy – https://www.birmingham.ac.uk/international/bia/presessional/index.aspx
For additional information on postgraduate studying at University of Birmingham please click - https://www.birmingham.ac.uk/study/postgraduate
For additional information on research at the College of Medical and Dental Sciences please click – https://www.birmingham.ac.uk/research/activity/mds/index.aspx
For additional information on research in the Institute of Cardiovascular Sciences please click – https://www.birmingham.ac.uk/research/cardiovascular-sciences/index.aspx
Funding Notes
Applicants should indicate 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 who wish to apply for their own funding (e.g. Islamic Development Bank International PhD Scholarships, China Scholarship Council).
We would only consider applications from prospective students with:
- a good biomedical degree, with interests in any of the areas above,
- good command of the English language as outlined in the postgraduate prospectus,
- a source of funding to cover tuition and bench fees.
We would only consider applications from prospective students with:
- a good biomedical degree, with interests in any of the areas above,
- good command of the English language as outlined in the postgraduate prospectus,
- a source of funding to cover tuition and bench fees.
References
References:
[1] M. Ackers-Johnson, P.Y. Li, A.P. Holmes, S.M. O'Brien, D. Pavlovic, R.S. Foo, A Simplified, Langendorff-Free Method for Concomitant Isolation of Viable Cardiac Myocytes and Nonmyocytes From the Adult Mouse Heart, Circ Res, 119 (2016) 909-920.
[2] J.P. Law, A.M. Price, L. Pickup, A. Radhakrishnan, C. Weston, A.M. Jones, H.M. McGettrick, W. Chua, R.P. Steeds, L. Fabritz, P. Kirchhof, D. Pavlovic, J.N. Townend, C.J. Ferro, Clinical Potential of Targeting Fibroblast Growth Factor-23 and alphaKlotho in the Treatment of Uremic Cardiomyopathy, J Am Heart Assoc, 9 (2020) e016041.
[3] C. O'Shea, S.N. Kabir, A.P. Holmes, M. Lei, L. Fabritz, K. Rajpoot, D. Pavlovic, Cardiac optical mapping - State-of-the-art and future challenges, Int J Biochem Cell Biol, (2020) 105804.
[4] C. O'Shea, J. Winter, A.P. Holmes, D.M. Johnson, J.N. Correia, P. Kirchhof, L. Fabritz, K. Rajpoot, D. Pavlovic, Temporal irregularity quantification and mapping of optical action potentials using wave morphology similarity, Prog Biophys Mol Biol, (2019).
[5] C. O'Shea, D. Pavlovic, K. Rajpoot, J. Winter, Examination of the Effects of Conduction Slowing on the Upstroke of Optically Recorded Action Potentials, Front Physiol, 10 (2019) 1295.
[6] C. O'Shea, A.P. Holmes, T.Y. Yu, J. Winter, S.P. Wells, B.A. Parker, D. Fobian, D.M. Johnson, J. Correia, P. Kirchhof, L. Fabritz, K. Rajpoot, D. Pavlovic, High-Throughput Analysis of Optical Mapping Data Using ElectroMap, J Vis Exp, (2019).
[7] C. O'Shea, A.P. Holmes, J. Winter, J. Correia, X. Ou, R. Dong, S. He, P. Kirchhof, L. Fabritz, K. Rajpoot, D. Pavlovic, Cardiac Optogenetics and Optical Mapping - Overcoming Spectral Congestion in All-Optical Cardiac Electrophysiology, Front Physiol, 10 (2019) 182.
[8] C. O'Shea, A.P. Holmes, T.Y. Yu, J. Winter, S.P. Wells, J. Correia, B.J. Boukens, J.R. De Groot, G.S. Chu, X. Li, G.A. Ng, P. Kirchhof, L. Fabritz, K. Rajpoot, D. Pavlovic, ElectroMap: High-throughput open-source software for analysis and mapping of cardiac electrophysiology, Sci Rep, 9 (2019) 1389.
[9] Hall, C., Law, J. P., Reyat, J. S., Cumberland, M. J., Hang, S., Vo, N. T. N., Raniga, K., Weston, C. J., O'shea, C., Townend, J. N., Gehmlich, K., Ferro, C. J., Denning, C. & Pavlovic, D. 2023. Chronic activation of human cardiac fibroblasts in vitro attenuates the reversibility of the myofibroblast phenotype. Sci Rep, 13, 12137.
[1] M. Ackers-Johnson, P.Y. Li, A.P. Holmes, S.M. O'Brien, D. Pavlovic, R.S. Foo, A Simplified, Langendorff-Free Method for Concomitant Isolation of Viable Cardiac Myocytes and Nonmyocytes From the Adult Mouse Heart, Circ Res, 119 (2016) 909-920.
[2] J.P. Law, A.M. Price, L. Pickup, A. Radhakrishnan, C. Weston, A.M. Jones, H.M. McGettrick, W. Chua, R.P. Steeds, L. Fabritz, P. Kirchhof, D. Pavlovic, J.N. Townend, C.J. Ferro, Clinical Potential of Targeting Fibroblast Growth Factor-23 and alphaKlotho in the Treatment of Uremic Cardiomyopathy, J Am Heart Assoc, 9 (2020) e016041.
[3] C. O'Shea, S.N. Kabir, A.P. Holmes, M. Lei, L. Fabritz, K. Rajpoot, D. Pavlovic, Cardiac optical mapping - State-of-the-art and future challenges, Int J Biochem Cell Biol, (2020) 105804.
[4] C. O'Shea, J. Winter, A.P. Holmes, D.M. Johnson, J.N. Correia, P. Kirchhof, L. Fabritz, K. Rajpoot, D. Pavlovic, Temporal irregularity quantification and mapping of optical action potentials using wave morphology similarity, Prog Biophys Mol Biol, (2019).
[5] C. O'Shea, D. Pavlovic, K. Rajpoot, J. Winter, Examination of the Effects of Conduction Slowing on the Upstroke of Optically Recorded Action Potentials, Front Physiol, 10 (2019) 1295.
[6] C. O'Shea, A.P. Holmes, T.Y. Yu, J. Winter, S.P. Wells, B.A. Parker, D. Fobian, D.M. Johnson, J. Correia, P. Kirchhof, L. Fabritz, K. Rajpoot, D. Pavlovic, High-Throughput Analysis of Optical Mapping Data Using ElectroMap, J Vis Exp, (2019).
[7] C. O'Shea, A.P. Holmes, J. Winter, J. Correia, X. Ou, R. Dong, S. He, P. Kirchhof, L. Fabritz, K. Rajpoot, D. Pavlovic, Cardiac Optogenetics and Optical Mapping - Overcoming Spectral Congestion in All-Optical Cardiac Electrophysiology, Front Physiol, 10 (2019) 182.
[8] C. O'Shea, A.P. Holmes, T.Y. Yu, J. Winter, S.P. Wells, J. Correia, B.J. Boukens, J.R. De Groot, G.S. Chu, X. Li, G.A. Ng, P. Kirchhof, L. Fabritz, K. Rajpoot, D. Pavlovic, ElectroMap: High-throughput open-source software for analysis and mapping of cardiac electrophysiology, Sci Rep, 9 (2019) 1389.
[9] Hall, C., Law, J. P., Reyat, J. S., Cumberland, M. J., Hang, S., Vo, N. T. N., Raniga, K., Weston, C. J., O'shea, C., Townend, J. N., Gehmlich, K., Ferro, C. J., Denning, C. & Pavlovic, D. 2023. Chronic activation of human cardiac fibroblasts in vitro attenuates the reversibility of the myofibroblast phenotype. Sci Rep, 13, 12137.
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