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Further insight into the human atrioventricular node in health and disease - from molecules (miRs, lcRNA, mRNA) to whole tissue imaging with aid of A.I.

Personal profile

Biography

Halina Dobrzynski obtained a B.Sc. in Biological Sciences (Physiology) in 1996 and a Ph.D. in Biomedical Sciences (Cellular Cardiology) in 2000. Both degrees were obtained from the University of Leeds, UK. For five years she worked as a post-doctoral fellow at the University of Leeds. In 2005 she moved to the University of Manchester as a Lecturer in Cardiac Anatomy and Pathophysiology. Since August 2011 she is a Senior Lecturer in Cardiovascular Sciences, School of Medicine, University of Manchester. Her main focus is the macro- and micro- anatomy and molecular biology of the specialised electrical system of the heart - the cardiac conduction system - in health, ageing and disease in human and many small lab species as well as larger animals such as goat, cat, camel. Since 2019 she has also been affiliated with Department of Anatomy, Jagiellonian University, Cracow, Poland, and has a visiting professor post. She obtained a D.Sc. in Biomedical and Health Sciences in 2023 from Jagiellonian University.       

Other posts held:

2008-2012  Visiting Researcher, Washington University, St. Louis, USA

2005   Visiting Research Associate, National Institutes of Health, Baltimore, USA

2005  Visiting Research Associate, Washington University, St. Louis, USA

2002  Visiting Research Associate, Case Western Reserve University, Cleveland, USA

1996  Guest Ph.D. student, Research Institute of Environmental Medicine, Nagoya University, Japan

1995  Research Assistant, Department of Histopathology, Leeds General Infirmary, UK

Methodological knowledge

Halina's expertise is in macro- and micro- anatomy, immuno-histo/cyto-chemistry, molecular biology in relation to the conduction system of the heart has been sought by many laboratories throughout the world. She has recently been applying innovative image technology to visualise human, mice, pigs and cat hearts in 3D with aid of microCT, Amira, AI, VR, Microsoft HoloLense2.

 

Research interests

Halina focuses on anatomical and functional properties and cellular and molecular make-up of the cardiac conduction system of the heart in sickness and in health using a variety of techniques including well established techniques such as electrophysiology (in vivo and ex vivo ECG), histology, immunohistochemistry, Western blotting, molecular biology and recently microCT with aid of AI, VR and mixed reality.

The current focus of her research is the molecular make-up of the human sinoatrial and atrioventricular nodes and HIS-Purkinje system, as well as functional and structual changes in the cardiac conduction system in health, aging and disease in small laboratory animals. Her research has been sponsored by the BHF, NIH, Medtronic Inc, BBSRC, Leducq Foundation.

The current research group:

4 PhD students and 1 Postdoctoral Fellows.

Past supervision/co-supervision of PhD students and post-doctoral fellows:

2005-2006      

S. Yoo (PhD student); present position: Not known 

2005-2009      

H. Musa (post-doc); present position: Not known

2005-2009      

J. Tellez (post-doc); present position: NHS Clinical Scientist, UK 

2005-2009      

J. Yanni (PhD student); present position:  Clinician, NHS, UK

2005-2009      

E. Abd Allah (PhD student); present position: Lecturer, Egypt

2005-2009      

I. Greener (post-doc); present position: Not known

2005-2009      

N. Chandler (PhD student); present position: NHS Clinical Scientist, UK 

2006-2009      

G. Morris (PhD student); present position: Cardiologist, Australia 

2005-2010      

S. Inada (post-doc); present position: Scientist, Japan

2008-2011      

O. Fedorenko (post-doc); present position: Scientist, Russia

2008-2023       

A. Atkinson (MPhil/PhD student); present position: Research Fellow, University of Manchester, UK 

2009-2012      

O. Monfredi (PhD student); present position: Cardiologist, USA

2009-2012      

G. Hao (PhD student); present position: Scientist, China

2011-2014       

I. Temple (PhD student); present position: Cardiologist, NHS, UK

2011-2014      

Z. Borbas (PhD student); present postion: Cardiologist, NHS, UK

2012-2016       

Y. Saeed (PhD student); present position: Cardiologist, Pakistan

2012-2016      

M. Choudhury (PhD student); present position: Cardiologist, NHS, UK

2013-2017       

Y. Zhang (PhD student); present position: Scientist, China

2015-2019       

M. Petkova (PhD student); present position: Clinical Scientist, NHS, UK

2017-2022     

A.J. Aminu (PhD student); present postition: Medical Writer/Scientist, UK    

Invited talks:

2019                

Ohio State University, USA

Symposium on Cardiac Conduction System, Reykjavik, Iceland

Summer Undergraduate School, Moscow University, Russia

2018

The Third White Sea Comparative Physiology Summer School, White Sea Biological Station (MSU), Republic of Karelia, Russia  

University of Minnesota and Medtronic plc, Minneapolis,                                USA 

2017

Symposium on Cardiac Arrhythmia, University of Copenhagen, Denmark  

2016

American Heart Association, New Orleans, USA

2015                 

Symposium on Advances in Cardiac Structure and Function, Aarhus University Hospital, Denmark

2015               

39th meeting of the ESC Working Group on Cardiac Cellular Electrophysiology, Milan, Italy

2014

European Society of Cardiology Congress, Barcelona, Spain

2012

University of Bordeaux, France

2012

University of Minnesota, USA

2011

Leeds University, UK

2011

Newcastle University, UK

Heart Rhythm meeting, San Francisco, USA

Cardiology Meets Physics and Mathematics meeting, Koscielisko, Poland

2010

International Symposium on Arrhythmia and Heart Failure, University of Nagoya, Japan

2009

Medical University of South Carolina, Charleston, USA

Medtronic, Inc., Minneapolis, USA

2008

Faculty of Medicine, INSERM Nantes, France

International Society for Heart Research, Athens, Greece

Washington University, St Louis, USA

2007

University of Warsaw, Poland

International Meeting of Physiological Society, Manchester, UK

Symposium in honour of Professor R.H. Anderson; University College London, UK

2006

University of Würzburg, Germany

Grants (current and past):

~£4,635,960. Leducq programme grant network member. FANTASY; USA/Europenan network; 2019-2024.

£109,219; PI on the BHF project grant for Miss A. Juliet Aminu (PhD student): Mapping of the human cardiac conduction system; 2018-2022).

~£532,228; Co-applicant on the NIH grant. Integration of structure and signaling in cardiac pacemaker function. Vadim Fedorov, USA (PI); 2018-2022.

~£188,158. Co-investigator on a project sponsored by Zayed Center, UAE. The molecular basis of diabetic cardiomyopathy. Professor Frank Christopher Howarth, UAE (PI); 2018-2022.

£1,326,626. PI on the BHF 3-year programme grant: Control of ion channel expression in the cardiac conduction system in disease – search for potential new therapeutic targets. Professor M.R. Boyett (was PI; left in August 2019); 2018-2020. Other co-applicants: Dr. Elisabeth J. Cartwright, Dr. Xin Wang, Dr. Delvac Oceandy, Professor Sam Griffiths-Jones, Dr. Alicia D’Souza. 

£2,500,000; BHF 4 year PhD studentship programme, University of Manchester (2017-2020 intakes). Dr. EJ Cartwright (PI).

£109,219; PI on the BHF project grant for Miss Maria Petkova (PhD student): Investigation into the expression and function of key microRNAs in the human cardiac conduction system; 2015-2018.

~£300,000. Collaborator on a project sponsored by Russian Science Foundation. Investigation of the role of microRNA in structural and functional maturation of cardiac pacemaker and the possibility of cardiac cells reprogramming by microRNA for correction of rhythm disturbances. Dr. Vladislav Kuzmin, Russia (PI); 2019-2021.

£212,172. PI on the BHF project grant: Why Does Heart Block Occur at Night (Especially in Athletes)?; Professor M.R. Boyett (was PI left August 2019); 2017-2020. Other co-applicants: Dr. Alicia D’Souza, Dr. Elisabeth Cartwright. Professor Hugh Piggins (was also co-applicant – moved to the University of Bristol). PG/17/29/32945.

£118,243; PI on the BHF project grant: Detailed 3D modelling of human cardiac anatomy with emphasis on the conduction system using micro-Computer Tomography and mathematical modelling techniques - variation with ageing and heart failure; 2017-2019.

£200,000; Co-applicant on Cariplo Foundation: ACROSS – cardiac pacemaker ageing: cellular and molecular basis; Professor Dario DiFrancesco (PI); 2015-2018.

£214,177; Co-applicant on the BHF project grant: Why do bradyarrhythmias occur at night? An intrinsic circadian clock in the cardiac conduction system? Professor M.R. Boyett (PI); 2015-2018.

£221,669; Co-applicant on the BHF project grant: Molecular mechanisms underlying exercise training-induced arrhythmias. Professor M.R. Boyett (PI); 2014-2017.

£150,000; Co-applicant on the BHF project grant; Professor G.A. Ng (PI); 2014-2016.

£291,443; Co-applicant on the BHF project grant: Sinoatrial node dysfunction in ageing and failing hearts - the role of the membrane and Ca2+ clocks;Professor M. R. Boyett (PI); 2013-2016. 

£1,148,308; Co-applicant on the BHF programme grant: Mapping cardiac conduction system disease; Professor M.R. Boyett (PI), 2011-2016.

£200,000; Co-applicant the BHF project grant: Biopacemakers: new targets and new mechanisms; Dr. Gilliam M. Morris (PI); 2012-2015.

£128,690; Co-applicant on the BHF project grant: The molecular basis of arrhythmogenesis in tetralogy of Fallot. Clinical Research Training Fellowship for Dr. Haiko Schneider (PI); 2012-2015.

£1440; PI on Biomedical Vacation Scholarships for Mr Vinci Naruka; the Wellcome Trust: Anatomical mapping of the Purkinje fibers in health and heart failure;summer 2014.

£15,000; PI on a project grant; Novartis, Switzerland: Expression of novel receptors in the human sinoatrial node;2013-2014.

£50,000; Collaborator; the Polish Ministry of Education project: To treat better elderly subjects with cardiovascular deseases: is nebivolol more effective than metoprolol? Dr. Michal Maczewski (PI), University of Warsaw, Poland; 2011-2014.

£229,499; PI on the BHF project grant: Charaterisation of the structural and functional properties of subsidiary atrial pacemakers in goat model of sinus node dysfunction; 2010-2013.

£3,000; Co-PI with Professor Dario DiFrancesco on a symposium sponsored by the IUPS: Molecular basis of cardiac conduction system disease; Birmingham, UK; July 2013.

£1440; PI on Biomedical Vacation Scholarships for Miss Sandy Chu; the Wellcome Trust: Anatomical mapping of the cardiac conduction system within tissue sections through whole human heart in order to produce 3D model; summer 2012.

£154,571; Co-applicant on a PoP project; UMIP: A virtual whole human heart model for drug cardiotoxicity testing; Professor M. R. Boyett (PI). 2011-2012.

£260,372. Co-applicant on the BHF project grant: Effect of athletic training on the cardiac conduction system: ups and downs. Professor M. R. Boyett (PI); 2010-2013.

£200,000; Co-applicant on a project grant from Astra Zeneca, UK: Computer modelling of canine ventricular action potentials;Professors M. R. Boyett (PI); 2009-2012.

£173,319; PI on the BHF project grant: Functional and molecular investigation into the arrhythmogenic properties of the atrioventricular ring tissue;2008-2011.

$1,000000; Consultant on a project from the National Institute of Health, USA: Structure and function of the pacemaker and conduction system of the heart; Professor I. Efimov (PI) at Washington University, St Louis, USA; 2008-2012.      

£1,078,734; Co-applicant on the BHF programme grant: Molecular mapping of the pacemaker and conduction system of the heart in health and disease;Professor M.R. Boyett (PI); 2006-2011.

$149,970; PI on a project grant from Medtronic, Inc., USA: Molecular mapping and 3D reconstruction of the human atrioventricular node; 2006-2009

$111,321; PI on a project grant Medtronic, Inc., USA: Molecular mapping and 3D reconstruction of the human sinus node; 2005-2008.

£86,626; PI on a research equipment grant; Faculty of Medical & Human Sciences, University of Manchester; 2006-2007.

£14,523; PI on a research grant; Faculty of Medical & Human Sciences, University of Manchester; 2005-2007.

£22,000; PI on a two-day international Focused Physiological Society meeting: The centenary of the discovery of the sinoatrial and atrioventricular nodes; University of Manchester. Sponsored by the Physiological Society, the BHF, Servier and Medtronic; September 2007.

Further information

Teaching and administrative duties at University of Manchester:

2021-present    Human Tissue, Designated person, Cardiovascular Sciences

2021-2022        Mentor on the Manchester Gold Staff programme

2017-present    Health and Safety Deputy, Cardiovascular Sciences

2017-2020        Student Conduct and Discipline Committee (Chair and Panel member)

2011-present     Radiation Protection Supervisor, Cardiovascular Sciences

2010-2013         Member of Research Ethics Committee

2010-present    Tutor for Professional and Personal Development, Medical Students, Phase 1

2009-present   Interviewing Medical School Applicants

2009-present   Tutor on MRes, MSc courses across Faculty of Biology, Medicine and Health

2005-2015       Problem Based Learning Tutor to Medical Students, School of Medicine

2005-present   Supervisor of undergraduate project students, Faculty of Medical, Biological and Human Sciences

2005-present   Teaching anatomy, histology, immunocyto/histochemistry, molecular biology and general cardiac biology/physiology to undergraduate and postgraduate students and postdoctoral fellows within Manchester University, nationally and internationally.

Reviewer for scientific journals:

2015-present               Journal of Anatomy

2010-present               American Journal of Physiology

2009-present               Experimental Physiology

2009-present               Histology & Histopathology

2008-present               Circulation

2008-present               Circulation Research

2007-present               Journal of Cellular Physiology

2006-present               Cardiovascular Research

2005-present               Journal of Molecular & Cellular Cardiology

Member of Editorial Board:

2013-present               Frontiers in Physiology 

External grant referee:

2011-present               The Netherlands Organisation for Health Research and Development (ZonMw)

2015 (December)             The Welcome Trust, UK                                                             

Membership:

2014-present               Member of British Society of Cardiovascular Research and International Society of Heart Rhythm

2014-present               Member of European Society of Cardiology

2016-present               Member of Physiological Society 

Awards:

Best pre-clinical teacher of 2014, University of Manchester

Public engagement:

1. Science Ambassador's Dinner sponsored by The Ogden Trust to promote science for young people in Bury, 26 March 2014, Bury Grammar School 

2. Sixth Form Lecture on "What makes the heart beat?"

- Tuesday 29 November, 2011, Burnley Sixth Form College, UK

- Thursday 28 November, 2013, Cheadle College, UK

- Tuesday 4 February 2014, Bury Grammar School Girls, UK

3. Community Open Day, Saturday 6 July 2013, University of Manchester, UK

4. The Body Experience, Saturday 16 March 2013, Manchester Museum, UK

5. Manchester Science Spectacular, Saturday 29 October 2011, Manchester Museum, UK

Overview

General research profile

Structure, function and clinical relevance of the cardiac conduction system, including the atrioventricular ring and outflow tract tissues

It is now over 100 years since the discovery of the cardiac conduction system, consisting of three main parts, the sinus node, the atrio-ventricular node and the His–Purkinje system. The system is vital for the initiation and co-ordination of the heartbeat. Over the last 2 decades, immense strides have been made in our understanding of the cardiac conduction system. It has been shown that the system has a unique embryological origin, distinct from that of the working myocardium, and is more extensive than originally thought with additional structures: atrio-ventricular rings, a third node (retro-aortic node) and pulmonary and aortic sleeves. It has been shown that the expression of ion channels, intracellular calcium-handling proteins and gap junction channels in the system is specialised (different from that in the ordinary working myocardium), but appropriate to explain the functioning of the system, although there is continued debate concerning the ionic basis of pacemaking. We are beginning to understand the mechanisms (fibrosis and remodeling of ion channels and related proteins) responsible for dysfunction of the system (bradycardia, heart block and bundle branch block) associated with atrial fibrillation and heart failure and even athletic training. Equally, we are beginning to appreciate how naturally occurring mutations in ion channels cause congenital cardiac conduction system dysfunction. Finally, current therapies, the status of a new therapeutic strategy (use of a specific heart rate lowering drug) and a potential new therapeutic strategy (bio-pacemaking) are of great interests globally.

Expertise related to UN Sustainable Development Goals

In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):

  • SDG 3 - Good Health and Well-being
  • SDG 4 - Quality Education
  • SDG 16 - Peace, Justice and Strong Institutions
  • SDG 17 - Partnerships for the Goals

Areas of expertise

  • QM Human anatomy
  • cardiac conduction system
  • fibrosis
  • QP Physiology
  • ion channels
  • conduction system
  • RB Pathology
  • Heart Failure
  • arrhythmia
  • conduction system

Research Beacons, Institutes and Platforms

  • Digital Futures
  • Christabel Pankhurst Institute

Keywords

  • Cardiac conduction system
  • Imaging
  • Electrophysiology
  • Ageing
  • Heart Failure
  • biology medicine and health

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