Jacky CK Fung

Hypertrophic cardiomyopathy (HCM) affects at least 1 in 500 of the global population and is the most common cause of sudden cardiac death in the young¹. HCM is an autosomal dominant disease characterised by cardiomyocyte hypertrophy, disarray, and interstitial fibrosis. It is commonly associated with archetypical single mutations in genes encoding sarcomeric proteins resulting in enhanced myofilament calcium sensitivity and altered energetics and metabolism^2-4. Chronic disruption of myocyte homeostasis leads to cell hypertrophy as a compensatory mechanism^5,6. Furthermore, this intracellular defect could cause intercellular disorganisation (i.e., myocyte disarray). Collagen deposition is initially required to maintain tissue integrity. However, unresolved and accumulated interstitial fibrosis directly affects cardiac function and rhythm depending on its location and severity. As a result, cardiac diastolic dysfunction is commonly found in HCM patients with the potential to develop into systolic dysfunction and heart failure^7,8. Although cardiomyocyte hypertrophy and disarray can be explained by those sarcomeric mutations, the development of interstitial fibrosis, which may have a direct detrimental impact towards heart contractility, remains poorly defined. Currently, I am focusing on revealing the potential involvement of B-lymphocytes in triggering the late-stage transition in HCM in the laboratory of Professor Hugh Watkins and co-supervised by Professor Charles Redwood and Dr Ying-Jie Wang.

I have a background in cardiac research, novel therapeutics, and biochemistry. I completed my postgraduate degree at Imperial College London (MSc in Gene, Drug, Stem Cells-Novel Therapies) and worked as a postgraduate researcher at the National Heart and Lung Institute (NHLI) under the supervision of Professor Tristan Rodrigeuz and Dr Susanne Sattler. I focused on revealing the involvement of adaptive auto-reactivity against the heart in a model of mitochondrial-mediated cardiomyopathy. The research outcome was showcased at the British Heart Foundation Reflection of Research 2022.   

1. Aro, A.L., et al. Population Burden of Sudden Death Associated With Hypertrophic Cardiomyopathy. Circulation 136, 1665-1667 (2017).

2. Watkins, H., Ashrafian, H. & Redwood, C. Inherited cardiomyopathies. N Engl J Med 364, 1643-1656 (2011).

3. Redwood, C.S., Moolman-Smook, J.C. & Watkins, H. Properties of mutant contractile proteins that cause hypertrophic cardiomyopathy. Cardiovasc Res 44, 20-36 (1999).

4. Seidman, J.G. & Seidman, C. The genetic basis for cardiomyopathy: from mutation identification to mechanistic paradigms. Cell 104, 557-567 (2001).

5. Crawford, P.A. & Schaffer, J.E. Metabolic stress in the myocardium: adaptations of gene expression. J Mol Cell Cardiol 55, 130-138 (2013).

6. Ruwhof, C. & van der Laarse, A. Mechanical stress-induced cardiac hypertrophy: mechanisms and signal transduction pathways. Cardiovasc Res 47, 23-37 (2000).

7. Olivotto, I., Cecchi, F., Poggesi, C. & Yacoub, M.H. Patterns of disease progression in hypertrophic cardiomyopathy: an individualized approach to clinical staging. Circ Heart Fail 5, 535-546 (2012).

8. Burchfield, J.S., Xie, M. & Hill, J.A. Pathological ventricular remodeling: mechanisms: part 1 of 2. Circulation 128, 388-400 (2013).

• BBC Science Focus " Stellar constellation of Blood Vessels wins British Heart Foundation Photography Prize"