||Professor Michael Ferenczi |
Vice-Dean, Faculty Affairs
Chair, Nanyang Technological University Senate
Professor of Medical Sciences
Principal Investigator, Muscle and Cardiac Biophysics Laboratory
- Dr Song Weihua, PhD, Senior Research Fellow
- Dr Yu Haiyang, PhD, Research Fellow
- Mufeeda Changaramvally Madathummal, PhD student
Professor Ferenczi has been Assistant Dean, Years 1 & 2 since 2012 when he joined Lee Kong Chian School of Medicine (LKCMedicine) from his post at Imperial College London to help set up Singapore’s newest Medical School. He plans and supervises the delivery of teaching to undergraduate medical students in their first two years of the MBBS Course and is Lead for ‘Scholarly Projects’, a research activity that all students undertake in their year 4. Prof Ferenczi is involved in the development of the graduate programme in LKCMedicine and is the elected Chair of Nanyang Technological University (NTU) Senate as well as Chair of Senate Committee on Research.
Prior to joining LKCMedicine, NTU in August 2012, Prof Ferenczi was Professor of Physiological Sciences at Imperial College London, a position held since 2001. He retains a Visiting Professorship at Imperial College. As an enthusiastic teacher in the Faculty of Medicine, he held formal responsibilities for the delivery of undergraduate teaching, including Head of the 'Molecules, Cells and Disease' Theme for MBBS students in Years 1 and 2, and Head of Year 4, the year during which medical students take a break from clinical training to undergo a Science year and gain a B.Sc. Degree in a speciality of their choice.
Prof Ferenczi was Head of the Molecular Medicine Section at the National Heart and Lung Institute of Imperial College with overall management responsibility for ten Principal Investigators and about 80 scientists who were exploring a variety of biological systems and disease processes using basic science techniques such as molecular biology, animal models and advanced optical microscopies. Within the Molecular Medicine Section, Prof Ferenczi ran the Muscle Biophysics laboratory. His research is now concentrating on the new laboratory of Cardiac and Muscle Biophysics in LKCMedicine’s Experimental Medicine Building in NTU. Prof Ferenczi successfully competed for a number of grants from MoE, including Tier 1 and Tier 2 awards, totaling more than S$1 Million (Dec 2016) as well as a share in a NRF-CRP award.
Prior to Imperial College, Prof Ferenczi was a Research Scientist at the United Kingdom Medical Research Council's National Institute for Medical Research (UK MRC NIMR) in Mill Hill, London (1983-2001). Previously he had spent three years at the University of Pennsylvania, Philadelphia after obtaining his Ph.D. in the Physiology Department at University College London in 1979.
Prof Ferenczi’s interest is the understanding of the molecular mechanism of movement in biological systems. Since muscle is an organ specialised in turning chemical energy into movement, his focus is on understanding the biophysical processes at the root of movement generation in muscle and in the heart. His laboratory uses muscle cells and myofibrils from a variety of sources, caged-compounds, fluorescent reporter probes, low angle X-ray diffraction at ESRF, FLIM (Fluorescence Lifetime Imaging Microscopy) and Second Harmonic Generation microscopy.
The cardiac engine: The Cardiac and Muscle Biophysics laboratory in LKCMedicine focuses on the behaviour of cardiac molecular motors, to explain essential molecular mechanisms. Prof Ferenczi and his team investigate mechanisms that underlie the Frank-Starling Law of the Heart, mechanisms by which genetic defects in sarcomeric proteins result in cardiac conditions such as hypertrophic cardiomyopathies and mechanisms which underlie the effect of protein phosphorylation on cardiac performance, the signalling pathways and disease progression. The aim is to develop therapeutic strategies to reduce the occurrence and alleviate the symptoms of cardiac disease.
Research collaborations are ongoing, both within and outside Singapore. For example Prof Ferenczi and his team collaborate with:
A number of PhD projects are available in the laboratory. An example is shown below:
TITLE: The role of RLC in age-related heart failure progression
AIM: understand the molecular mechanism by which contractile dysfunction occurs during age-related heart failure progression. Specifically, we aim to characterize the role of phosphorylation of the regulatory light chain of myosin (RLC) as a modulator of heart failure progression and to test its potential as a therapeutic strategy.
SIGNIFICANCE: Data from the Singapore Ministry of Health (MOH) and Singapore Heart Foundation (SHF) shows that 15 people die of cardiovascular diseases every day comprising ~30% of all deaths. About 25% of hospital stays in Singapore are for cardiovascular reasons with HF being the major cardiac cause of hospitalization that increased by ~40% over the last decade, at great cost to individuals, their family and the Country. We have shown that RLC phosphorylation can improve muscle performance in vitro. But it is not known if RLC phosphorylation is an efficient strategy for therapy to improve or revert primary contractile defects during HF progression. Moreover, performing gene-targeted therapy for missense mutations that cause cardiac hypertrophy revealed that therapy at early stages of hypertrophy or younger age is crucial (60). This further suggests importance of understanding changes that occur during the progression of HF, especially at earlier stages, as we have proposed here to test from 48hrs to 16 weeks post-MI.
APPROACH: Major methods include (1) Mice expressing human beta-cardiac myosin heavy chain (Humanized mice); (2) Surgical induction of heart failure in humanized mice; (3) Testing the contractility of cardiac muscle fibers from humanized MYH7 mice and MyBPC3 knock-out mice; (4) Testing the effect of kinase intervention on cardiac trabeculae and the effect of exchanging optimally phosphorylated RLC into the trabeculae; (5) Quantification of RLC phosphorylation during heart failure progression;
This proposal connects molecules to physiology of heart failure progression towards mechanistic understanding and to discover improved strategies of therapeutic interventions. To our knowledge, this is the first opportunity to combine these approaches to explore progressive HF at molecular and physiological levels.
- Toepfer C., West T.G., Ferenczi M.A. (2016) Revisiting Frank-Starling: regulatory light chain phosphorylation alters the rate of force redevelopment (ktr) in a length-dependent fashion. Journal of Physiology DOI: 10.1113/JP272441.
- Toepfer C.N., Sikkel M.B., Caorsi V., Vydyanath A., Torre I., Copeland O.N., Lyon A.R., Marston S.B., Luther P.K., MacLeod K.T., West T.G., Ferenczi M.A. (2016) A post-MI power struggle: adaptations in cardiac power occur at the sarcomere level alongside MyBP-C and RLC phosphorylation American Journal of Physiology - Heart and Circulatory Physiology DOI: 10.1152/ajpheart.00899.2015.
Toepfer C., Caorsi V., Kampourakis T., Sikkel M.B., West T.G., Leung M.C., Al-Saud S.A., Macleod K.T, Lyon A.R., Marston S.B., Sellers J.R., Ferenczi M.A. (2013) Myosin regulatory light chain (RLC) phosphorylation change as a modulator of cardiac muscle contraction in disease. Journal of Biological Chemistry 288: 13446-13454; doi: 10.1074/jbc.M113.455444.