Investigating the Mechanisms for Cardiac Fibrosis Development

University of Birmingham

Institute of Cardiovascular Sciences

Project Description

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 by the EU consortium FibroTargets [link] 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].

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].

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 34 papers, 15 of which in the last 3 years. Dr Pavlovic leads a team of 2 postdoctoral researchers and 3 PhD students. He also acts as a mid-career lead for the International Society for Heart Research [link] and has run a highly successful Cardiovascular Webinar series [link].

For more information about the Pavlovic research group, the Institute of Cardiovascular Sciences please see:
Dr D Pavlovic Staff Profile
Our Research in Atrial Fibrillation and Heart Failure
Institute of Cardiovascular Sciences

Funding Information

This project is to be self-funded.

Eligibility Requirements

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.

Application Process

To apply, please submit your CV and a covering email/letter for consideration to Dr Davor Pavlovic ([email protected])

Supplementary Information

To find out more about studying for a PhD at the University of Birmingham, including full details of the research undertaken in each Institute, the funding opportunities for each subject, and guidance on making your application, you can now order your copy of the new Doctoral Research Prospectus.

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.

To apply for this PhD, please email d.pavlovic@bham.ac.uk.

Before sending your email, please double check you have followed all guidelines in this listing and have included a reference number if asked to do so.

Overview
Location