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Heart Protection

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Background

Acute myocardial infarction and heart failure are among the leading causes of death and disability in Singapore and worldwide. As such novel treatment strategies are required to protect the heart against the detrimental effects of acute ischaemia/reperfusion injury (IRI) and prevent the onset and progression of heart failure in order to preserve cardiac function and preventing the onset of heart failure. We use a translational approach to heart protection with the elucidation of underlying disease mechanisms and discovery of novel therapeutic targets using pre-clinical human IPSC, cells and animal disease models and investigate their therapeutic potential in proof-of-concept clinical studies and multi-centre clinical outcome randomised controlled trials.

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Prof Derek Hausenloy

Research Area

  • New targets for cardioprotection (Dr Sauri Hernandez-Resendiz, Mr Jasper Chua, Ms Fan Yu) – Discovering new treatments for protecting the diabetic and non-diabetic myocardium from the detrimental effects of acute ischemia/reperfusion injury and for preventing the onset and progression of heart failure.
  • Clinical cardioprotection and imaging studies (Dr Jun Chong) – Testing new cardioprotective intervention studies in Phase 2 and Phase 3 randomised clinical trials. Epidemiological studies to investigate clinical outcomes in AMI patients. Using cardiac MRI to provide insights into acute myocardial ischemia/reperfusion injury and assess efficacy of novel cardioprotective therapies.
  • Nanotechnology (Dr Shengjie Lu) - Developing novel nanoparticles to improve bioavailability and delivery of therapeutics to the ischaemic heart following acute myocardial infarction.
  • Diabetes and heart failure (Mr Shuo Cong, Ms En Ping Yap) - Discovering new treatments for preventing the onset and progression of diabetic cardiomyopathy and HFpEF.
  • Human iPSCs (Asst Prof Chrishan Ramachandra, Dr Alvin Yin, Dr Marie Mai Jia) - Cardiac disease modelling and phenotyping using iPSCs and small animal models - to identify and validate novel treatments for cardiomyopathies (e.g. hypertrophic cardiomyopathy, HFpEF, diabetic cardiomyopathy).
  • Peripheral arterial disease (Mr Gustavo Crespo-Avilan, Ms Ariel Ying, Mr Xiaomeng Wang) – Discovering new treatments for preventing the onset and progression of atherosclerosis and for inhibiting tunica intimal hyperplasia. Epidemiological studies to investigate clinical outcomes in PAD patients.

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Achievements

Awards

  1. Highly Cited Researcher 2018, 2020, and 2021 (awarded to top 1% of researchers)
  2. Dean's Excellence Award in Research 2019, Duke-NUS, Singapore 
  3. Fellow of the International Society of Heart Research (FISHR) since 2018
  4. European Society of Cardiology (ESC) Outstanding Achievement Award 2013

Grants

  1. Traditional Chinese Medicine Research Grant (TCMRG) - Electroacupuncture for heart protection: clinical application in patients undergoing cardiac bypass surgery – EA-CABG (PI Prof Derek Hausenloy) 2019-2022
  2. NHCS Centre Grant - PROgram for Transforming & Evaluating outcomes in CardiomeTabolic disease (PROTECT) 2021-2025
  3. NMRC Collaborative Centre Grant (NHCS, NHG-HI, and NUHCS) - Implementing a partnership in cardiovascular trials 2 (IMPACT-2) 2021-2025
  4. NRF CRP - REducing Diabetic macrovascUlar Complications duE to Peripheral Arterial Disease - REDUCE-PAD (PI Prof Derek Hausenloy) 2021-2025
  5. STaR Award - New treatments and strategies to prevent heart failure in diabetes (PI Prof Derek Hausenloy) 2022-2027
  6. NMRC Open Fund-Young Investigator Research Grant(OFYIRG)- Light-Activatable Theranostic Nanoparticles to Improve the Delivery and Cardioprotective Efficacy of Cytoprotective Peptides in Acute Myocardial Infarction. (PI Dr Shengjie Lu) 2019-2022

Publications

  1. Hausenloy DJ, Candilio L, Evans R, Ariti C, Jenkins DP, Kolvekar S, Knight R, Kunst G, Laing C, Nicholas J, Pepper J, Robertson N, Xenou X, Clayton T, Yellon DM. Remote Ischemic Preconditioning and Outcomes in Cardiac Bypass Surgery. N Engl J Med 2015 Oct 8;373(15):1408-17. IF 91.245
  2. Thielmann M, Sharma V, Al-Attar N, Bulluck H, Bisleri G, Jh Bunge J, Czerny M, …Hausenloy DJ. ESC Joint Working Groups on Cardiovascular Surgery and the Cellular Biology of the Heart Position Paper: Perioperative myocardial injury and infarction in patients undergoing coronary artery bypass graft surgery. Eur Heart J. 2017 Aug 14;38(31):2392-2407. IF 29.98
  3. Bulluck H, Chan MHH, Paradies V, Bryant JA, Hernández-Reséndiz S, Cabrera-Fuentes HA, Watson TJ, Chan MY, Tan JW, Hausenloy DJ. Impact of Cardioprotective Therapies on the Edema-Based Area at Risk by CMR in Reperfused STEMI. J Am Coll Cardiol. 2018 Jun 19;71(24):2856-2858. IF 24.094
  4. Nagel, E, Greenwood J, McCann GP, Shah AJ, Hussain ST, Plein S, Bucciarelli-Ducci C, Paul M, Westwood MA, Marber M, Richter WS, Puntmann VO, Shwenke C, Schulz-Menger J, Das R,  Hausenloy DJ, Steen H, Berry C.  Comparative Effectiveness of Magnetic Resonance Perfusion and Fractional Flow Reserve. N Engl J Med 2019 Jun 20;380(25):2418-2428. IF 91.245
  5. Davidson SM, Ferdinandy P, Andreadou I, Bøtker HE, Heusch G, Ibáñez B, Ovize M, Schulz R, Yellon DM, Hausenloy DJ*, Garcia-Dorado D*; CARDIOPROTECTION COST Action (CA16225). Multitarget Strategies to Reduce Myocardial Ischemia/Reperfusion Injury: JACC Review Topic of the Week. *Joint Senior Authors. J Am Coll Cardiol. 2019 Jan 8;73(1):89-99. IF 24.094
  6. Ibanez B, Aletras AH, Arai AE, Arheden H, Bax J, Berry C, Bucciarelli-Ducci C, Croisille P, Dall'Armellina E, Dharmakumar R, Eitel I, Fernández-Jiménez R, Friedrich MG, García-Dorado D, Hausenloy DJ, Kim RJ, Kozerke S, Kramer CM, Salerno M, Sánchez-González J, Sanz J, Fuster V. Cardiac MRI Endpoints in Myocardial Infarction Experimental and Clinical Trials: JACC Scientific Expert Panel. J Am Coll Cardiol. 2019 Jul 16;74(2):238-256. IF 24.094
  7. Hausenloy DJ, Kharbanda RK, Møller UK, Ramlall M, Aarøe J, ….Bøtker HE; CONDI-2/ERIC-PPCI Investigators. Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial. Lancet. 2019 Oct 19;394(10207):1415-1424. IF 79.321
  8. Kompa AR, Greening DW, Kong AM, McMillan PJ, Fang H, Saxena R, Wong RCB, Lees JG, Sivakumaran P, Newcomb AE, Tannous BA, Kos C, Mariana L, Loudovaris T, Hausenloy DJ*, Lim SY*. Sustained subcutaneous delivery of secretome of human cardiac stem cells promotes cardiac repair following myocardial infarction. Cardiovasc Res. 2020 Apr 6:cvaa088. doi: 10.1093/cvr/cvaa088. IF 10.787.
  9. Ramachandra CJA, Chua J, Cong S, Kp MMJ, Shim W, Wu JC, Hausenloy DJ. Human induced pluripotent stem cells for modelling metabolic perturbations and impaired bioenergetics underlying cardiomyopathies. Cardiovasc Res. 2020 May 4:cvaa125. doi: 10.1093/cvr/cvaa125. IF 10.787.
  10. Lopes RD, Alexander KP, Stevens SR, Reynolds HR, Stone GW, Pina IL, Rockhold FW, Elghamaz A, Lopez-Sendon JL, Farsky PS, Chernyavskiy AM, Diaz A, Phaneuf D, DeBelder MA, Ma YT, Guzman LA, Khouri M, Sionis A, Hausenloy DJ, Doerr R, Selvanayagam JK, Maggioni AP, Hochman JS, Maron D. Initial Invasive versus Conservative Management of Stable Ischemic Heart Disease Patients with a History of Heart Failure or Left Ventricular Dysfunction: Insights from the ISCHEMIA Trial. Circulation. 2020 Nov 3;142(18):1725-1735. IF 23.603
  11. Kalkhoran S, Kriston-Vizi J, Hernandez-Resendiz S, Crespo-Avilan GE, Rosdah AA, Lees JG, Simoes Da Costa JR, Ling NXY, Holien JK, Samangouei S, Chinda K, Yap EP, Riquelme JA, Ketteler R, Yellon DM, Lim SY, Hausenloy DJ. Hydralazine protects the heart against acute ischemia/reperfusion injury by inhibiting Drp1-mediated mitochondrial fission. Cardiovasc Res. 2021 Jan 2:cvaa343. doi: 10.1093/cvr/cvaa343. IF 10.787.
  12. Ramachandra CJA, Kp MMJ, Chua J, Hernandez-Resendiz S, Liehn EA, Gan LM, Michaëlsson E, Jonsson MKB, Ryden-Markinhuhta K, Bhat RV, Fritsche-Danielson R, Lin YH, Sadayappan S, Tang HC, Wong P, Shim W, Hausenloy DJ. Inhibiting cardiac myeloperoxidase alleviates the relaxation defect in hypertrophic cardiomyocytes. Cardiovasc Res. 2021 Mar 10:cvab077. doi: 10.1093/cvr/cvab077. IF 10.787.
  13. Silvain J, Zeitouni M, Paradies V, Zheng HL, Ndrepepa G, Cavallini C, Feldman DN, Sharma SK, Mehilli J, Gili S, Barbato E, Tarantini G, Ooi SY, von Birgelen C, Jaffe AS, Thygesen K, Montalescot G, Bulluck H, Hausenloy DJ. Cardiac procedural myocardial injury, infarction, and mortality in patients undergoing elective percutaneous coronary intervention: a pooled analysis of patient-level data. Eur Heart J. 2021 Jan 21;42(4):323-334. IF 29.98
  14. Figtree GA, Broadfoot K, Casadei B, Califf R, Crea F, Drummond GR, Freedman JE, Guzik TJ, Harrison D, Hausenloy DJ, Hill JA, Januzzi JL, Kingwell BA, Lam CSP, MacRae CA, Misselwitz F, Miura T, Ritchie RH, Tomaszewski M, Wu JC, Xiao J, Zannad F. A Call to Action for New Global Approaches to Cardiovascular Disease Drug Solutions. Eur Heart J. 2021 Apr 14;42(15):1464-1475. IF 29.98
  15. Bulluck H, Paradies V,…, Thygesen K, Hausenloy DJ. Prognostically relevant periprocedural myocardial injury and infarction associated with percutaneous coronary interventions: a Consensus Document of the ESC Working Group on Cellular Biology of the Heart and European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J. 2021 Jul 15;42(27):2630-2642. IF 29.98
  16. Lecour S, Andreadou I, Bøtker HE, Davidson SM, Heusch G, Ruiz-Meana M, Schulz R, Zuurbier CJ, Ferdinandy P, Hausenloy DJ; on behalf of the European Union-CARDIOPROTECTION COST ACTION CA16225. IMproving Preclinical Assessment of Cardioprotective Therapies (IMPACT) criteria: guidelines of the EU-CARDIOPROTECTION COST Action. Basic Res Cardiol. 2021 Sep 13;116(1):52. doi: 10.1007/s00395-021-00893-5. IF 17.165.
  17. Francis R, Chong J, Ramlall M, Bucciarelli-Ducci C, Clayton T, Dodd M, Engstrøm T, Evans R, Ferreira VM, Fontana M, Greenwood JP, Kharbanda RK, Kim WY, Kotecha T, Lønborg JT, Mathur A, Møller UK, Moon J, Perkins A, Rakhit RD, Yellon DM, Bøtker HE, Bulluck H, Hausenloy DJ. Effect of remote ischaemic conditioning on infarct size and remodelling in ST-segment elevation myocardial infarction patients: the CONDI-2/ERIC-PPCI CMR substudy. Basic Res Cardiol. 2021 Oct 14;116(1):59. doi: 10.1007/s00395-021-00896-2. IF 17.165.
  18. Schumacher D, Liehn EA, Nilcham P, Mayan DC, Rattanasopa C, Anand K, Crespo-Avilan GE, Hernandez-Resendiz S, Singaraja RR, Cook SA, Hausenloy DJ. A neutralizing IL-11 antibody reduces vessel hyperplasia in a mouse carotid artery wire injury model. Sci Rep. 2021 Oct 19;11(1):20674. doi: 10.1038/s41598-021-99880-y. IF 4.379