Dr Davor Pavlovic DPhil FHEA

Dr Davor Pavlovic

Institute of Cardiovascular Sciences
Lecturer in Cardiovascular Sciences

Contact details

Address
Institute of Cardiovascular Sciences
College of Medical and Dental Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
UK

Davor has joined University of Birmingham as a Lecturer in Cardiovascular Sciences within the Institute of Cardiovascular Sciences.

His primary research interest is to understand molecular mechanisms of ion transport in the heart and how these may be targeted to treat cardiovascular disease. Davor has published a number of research papers and review articles focused on regulation of ion homeostasis in normal physiology and disease, with a particular focus on heart failure, arrhythmias and cardiorenal syndrome.  For his work Davor has received awards by the International Society for Heart Research and European Society of Cardiology and is currently funded by the Wellcome Trust, Medical Research Council and British Heart Foundation.

Qualifications

  • Fellow of the Higher Education Academy 2013
  • DPhil Biochemistry 2005
  • BSc Biochemisty (1st) 2001

Biography

Dr Pavlovic gained his first class BSc (Hon) in Biochemistry from University of Huddersfield in 2001. During his undergraduate degree he spent a year working at Imperial College London in a laboratory of Prof Ten Feizi where he investigated the role of oligosaccharide ligands for proteins involved in innate and acquired immunity. He obtained his PhD from University of Oxford (Exeter College) under the guidance of the then head of department of Biochemistry Prof Raymond Dwek and Prof Nicole Zitzmann. At Oxford Dr Pavlovic worked with a Nobel Laureate Dr Baruch Blumberg where he showed that Hepatitis C virus p7 protein forms ion channels that can be blocked by long alkyl chain iminosugars. He then moved to King’s College London (St Thomas Hospital campus) and took up a post of a British Heart Foundation Research Fellow in the laboratory headed by Prof Michael Shattock, where he worked on regulation of the cardiac sodium pump. His work uncovered the role of protein called phospholemman in adrenergic, nitric oxide and phosphatase mediated regulation of the cardiac sodium pump in healthy and diseased hearts. In 2015, Dr Pavlovic was appointed as a Lecturer in Cardiovascular Sciences at the University of Birmingham.

Teaching

Here are video clips of four tutorials demonstrating Davor's teaching on the subjects of cardiac action potential, cardiac myocyte structure, cardiac contraction and membrane potential.

Research

Dr Pavlovic’s research is focused on three major themes:

- Regulation of the cardiac sodium pump

As the only quantitatively significant sodium efflux pathway out of cardiac cells, sodium pump is the primary regulator of intracellular sodium. The trans-membrane sodium gradient it establishes is essential for normal electrical excitability, numerous coupled-transport processes and, as the driving force for Na/Ca exchange, thus setting cardiac calcium load and contractility. As sodium influx varies with electrical excitation, heart rate and pathology, the dynamic regulation of sodium efflux is essential. Phospholemman, a 72 amino acid accessory protein that forms part of the sodium pump complex, is the key nexus linking cellular signaling to pump regulation. Phospholemman is the target of a variety of kinase and phosphatase-mediated post-translational modifications and these can dynamically alter the activity of the sodium pump. Current research is focused on identifying novel phosphatase-mediated regulatory pathways for the cardiac sodium pump and how these regulatory pathways are modified in disease.

- The role of Cardiotonic Steroids in the heart

Cardiotonic steroids are a new class of hormones that circulate in the blood and have the ability to bind and inhibit the sodium pump, thus regulating intracellular sodium in every living cell. During states of chronic volume expansion, such as chronic kidney disease or heart failure, cardiotonic steroids are elevated in the blood and have been implicated in development of cardiovascular disease. Current research is directed towards understanding the relationship between endogenous cardiotonic steroid concentrations in chronic kidney disease patients and development of cardiac dysfunction.

- Causes of Atrial Fibrillation

Atrial fibrillation is the most common sustained arrhythmia. Electrical and structural remodelling of the myocardium are the two main causes of atrial fibrillation development. Atrial fibrillation is mainly a left atrial disease and Pitx2c has been identified as the single most enriched gene in the left atrium, suggesting a relevant role of this gene for left atrial function in health and disease. Current research is focused on identifying whether Pitx2c is involved in the pathophysiology of atrial fibrillation.

PhD Students

Sian-Marie O’Brien
Started Sep 2015 – “Regulation of intracellular sodium in the atria”

Dannie Fobian
Started Sep 2016 – “Translating the effect of rate control therapy in atrial fibrillation: from cellular response to cardiac function”

Chris O’Shea 
Started Sep 2016 – “Developing a high-resolution optical mapping setup with integrated high-throughput analysis capabilites for dissecting molecular mechanisms of cardiac arrhythmias”  

Simon Wells 
Started Feb 2017 – “Cardiac estrogen synthesis and arrhythmia

Publications

Ackers-Johnson M, Li PY, Holmes AP, O'Brien SM, Pavlovic D and Foo RS. A Simplified, Langendorff-Free Method for Concomitant Isolation of Viable Cardiac Myocytes and Non-Myocytes from the Adult Mouse Heart. Circ Res. 2016 Aug 

Holmes AP, Yu YT, Tull S, Syeda F, Kuhlmann SM, O'Brien S, Patel P, Brain KL, Pavlovic D, Brown NA, Fabritz L and Kirchhof P (2016) A regional reduction in Ito and IKACh in the murine posterior left atrial myocardium is associated with action potential prolongation and increased ectopic activity. PLOS One May 5;11(5)

Thomassen M, Gunnarsson TP, Christensen PM, Pavlovic D, Shattock MJ and Bangsbo J (2016) Intensive training and reduced volume increases muscle FXYD1 expression and phosphorylation at rest and during exercise in athletes Am J Physiol Regul Integr Comp Physiol. Apr 1;310(7)

Medina RA, Mariotti E, Pavlovic D, Shaw KP, Eykyn TR, Blower PJ and Southworth RJ (2015) 64Cu-CTS: A Promising Radiopharmaceutical for the Identification of Low-Grade Cardiac Hypoxia by PET J Nucl Med. 2015 Jun;56(6):921-6.

Shattock M, Ottolia M, Bers M, Blaustein M, Boguslavskyi A, Bossuyt J, Bridge J, Chen-Izu Y, Clancy C, Edwards A, Goldhaber J, Kaplan J, Lingrel J, Pavlovic D, Philipson K, Sipido K and Xie ZJ (2015) Na+/Ca2+ exchange and Na+/K+-ATPase in the heart. Journal of Physiology Mar 15;593(6):1361-82

Pavlovic D (2014) The role of cardiotonic steroids in the pathogenesis of cardiomyopathy in chronic kidney disease. Nephron Clin Pract 128(1-2):11-21

Boguslavskyi A, Pavlovic D, Aughton K, Fuller W and Shattock MJ (2014) Cardiac hypertrophy in mice expressing unphosphorylatable phospholemman. Cardiovasc Res 104(1):72-82

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 9(5):e96909

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. J Mol Cell Cardiol 61:164-71

Pavlovic D, Fuller W and Shattock MJ (2013) Novel regulation of cardiac Na pump via phospholemman. J Mol Cell Cardiol 61:83-93