Key Personnel

RESEARCH FOCUS

Laboratory of Cardiac Epigenome, Molecular Epigenetics and Stress-gene Response.

Heart failure is a major cause of mortality and morbidity in the world today. Easily rivalling the severity of some forms of cancer, life expectancy for patients with heart failure at 5 years can be as poor as <50%. Novel targets are urgently needed for the heart failure drug discovery pipeline. Moreover, current therapy slows disease progression, but does not reverse the course of disease. Although heart failure can be caused by different originating causes including hypertension, diabetes, myocardial infarction and genetic mutations, it is nonetheless characterised by convergent processes such as fibrosis, angiogenesis and cell death. Similarly a consistent pattern of gene expression constitutes the myocardial genomic stress-response in the progression of heart failure. A hallmark for this myocardial genomic stress-response includes fetal gene reprogramming, upregulation of extracellular matrix genes and others.

The epigenome refers to “marks” on the genome including histone modifications and DNA methylation. Our group published the first evidence that differential DNA methylation exists in end-stage human cardiomyopathic hearts and correlates to changes in specific gene expression. By high-throughput sequencing, we have also published the first glimpse of genome-wide DNA methylation landscapes of the failing human heart. A major effort in the lab now is to deep dive and to establish the role of the cardiac epigenome and chromatin reorganization in heart failure onset and progression. To achieve this, we employ a host of genomic and molecular tools, with tractable in vitro and in vivo experimental models as well as human explant tissue to study the myocardial genomic and epigenomic stress response. Epigenetic tools represent a real potential for finding refreshing molecular therapeutic approaches that work to reverse the course of disease, rather than just slowing down its progression.

The recent large BMRC SPF Cardiovascular Research grant award consists of a Genetics/Epigenetics theme which our group leads. This has the ambitious aim of mapping out functional elements in the cardiac genome and epigenome, opening up a new and important area of cardiovascular research. We hope that all together our work will eventually lead to the identification of novel targets for future heart failure therapy.

In a separate translational programme, our lab was also responsible for establishing Singapore’s first Inherited Cardiac Conditions clinic based at the National University Heart Centre. This clinic makes use of high-throughput sequencing-based genetic test panels developed at the Genome Institute of Singapore.

EDUCATION

1992 MBBS, National University of Singapore

1997 MRCP, Royal College of Physicians UK

2000 MD University of Leicester UK

2003 CCT, Completetion of Specialist Training, Cambridge University Hospitals NHS Foundation Trust, UK

PROFESSIONAL APPOINTMENTS

2012-Associate Professor, Cardiovascular Research Institute, Yong Loo Lin School of Medicine, National University of Singapore

2012- Senior Consultant, National University Heart Centre, National University Healthcare System, Singapore

2012- Adjunct Senior Investigator, Genome Institute of Singapore

2012 Visiting Fellow, Department of Medicine, University of Cambridge, UK

2007-2012 British Heart Foundation Intermediate Fellow, Division of Cardiovascular Medicine, University of Cambridge, UK

2007-2012 Consultant Physician, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust

2003-2007 Wellcome Trust Advanced Fellow, Albert Einstein College of Medicine, NY

1999-2003 Specialist Registrar, Division of Cardiovascular Medicine and Clinical Pharmacology Unit, University of Cambridge

1997-1999 Junior Research Fellow, University of Leicester, UK

1996-1997 Senior House Officer, Department of Medicine, Kings College Hospital, London

HONOR AND AWARDS

2012 Fellow, American Heart Association

2012 Associate Member, EpiGeneSys EU Epigenetics systems biology programme

2006 Finalist, Katz Basic Science Research Prize, American Heart Association

2003 Philip White Award, British Cardiac Society

2001 Medical Research Society London Abstract Prize

1999 Grimshaw-Parkinson Trust Award, University of Cambridge, UK

COMPLETE PUBLICATION LIST

Reijnders MRF, Janowski R, Alvi M, Self JE, van Essen TJ, Vreeburg M, Rouhl RPW, Stevens SJC, Stegmann APA, Schieving J, Pfundt R, van Dijk K, Smeets E, Stumpel CTRM, Bok LA, Cobben JM, Engelen M, Mansour S, Whiteford M, Chandler KE, Douzgou S, Cooper NS, Tan EC, Foo R, Lai AHM, Rankin J, Green A, Lönnqvist T, Isohanni P, Williams S, Ruhoy I, Carvalho KS, Dowling JJ, Lev DL, Sterbova K, Lassuthova P, Neupauerová J, Waugh JL, Keros S, Clayton-Smith J, Smithson SF, Brunner HG, van Hoeckel C, Anderson M, Clowes VE, Siu VM, Ddd Study T, Selber P, Leventer RJ, Nellaker C, Niessing D, Hunt D, Baralle D "PURA syndrome: clinical delineation and genotype-phenotype study in 32 individuals with review of published literature." J Med Genet 2018 Feb ; 55(2) : 104-113
Abstract

Kam S, Bylstra Y, Forrest L, Macciocca I, Foo R "Experience of Asian males communicating cardiac genetic risk within the family." J Community Genet 2018 Jul ; 9(3) : 293-303
Abstract

Zhao RR, Ackers-Johnson M, Stenzig J, Chen C, Ding T, Zhou Y, Wang P, Ng SL, Li PY, Teo G, Rudd PM, Fawcett JW, Foo RSY "Targeting Chondroitin Sulfate Glycosaminoglycans to Treat Cardiac Fibrosis in Pathological Remodeling." Circulation 2018 Jun 05 ; 137(23) : 2497-2513
Abstract

Stenzig J, Schneeberger Y, Löser A, Peters BS, Schaefer A, Zhao RR, Ng SL, Höppner G, Geertz B, Hirt MN, Tan W, Wong E, Reichenspurner H, Foo RS, Eschenhagen T "Pharmacological inhibition of DNA methylation attenuates pressure overload-induced cardiac hypertrophy in rats." J Mol Cell Cardiol 2018 Jul ; 120 : 53-63
Abstract

Bylstra Y, Kuan JL, Lim WK, Bhalshankar JD, Teo JX, Davila S, Teh BT, Rozen S, Tan EC, Liew WKM, Yeo KK, Tan P, Saw SM, Cheng CY, Cook S, Foo R, Jamuar SS "Population genomics in South East Asia captures unexpectedly high carrier frequency for treatable inherited disorders." Genet Med 2018 Jul 02
Abstract

Tan WL, Lim BT, Anene-Nzelu CG, Ackers-Johnson M, Dashi A, See K, Tiang Z, Lee DP, Chua WW, Luu TD, Li PY, Richards AM, Foo RS "A landscape of circular RNA expression in the human heart." Cardiovasc Res 2017 Mar 01 ; 113(3) : 298-309
Abstract

Zhai W, Lim TK, Zhang T, Phang ST, Tiang Z, Guan P, Ng MH, Lim JQ, Yao F, Li Z, Ng PY, Yan J, Goh BK, Chung AY, Choo SP, Khor CC, Soon WW, Sung KW, Foo RS, Chow PK "The spatial organization of intra-tumour heterogeneity and evolutionary trajectories of metastases in hepatocellular carcinoma." Nat Commun 2017 Feb 27 ; 8 : 4565
Abstract

See K, Tan WLW, Lim EH, Tiang Z, Lee LT, Li PYQ, Luu TDA, Ackers-Johnson M, Foo RS "Single cardiomyocyte nuclear transcriptomes reveal a lincRNA-regulated de-differentiation and cell cycle stress-response in vivo." Nat Commun 2017 08 09 ; 8(1) : 225
Abstract

Jamuar SS, Kuan JL, Brett M, Tiang Z, Tan WL, Lim JY, Liew WK, Javed A, Liew WK, Law HY, Tan ES, Lai A, Ng I, Teo YY, Venkatesh B, Reversade B, Tan EC, Foo R "Incidentalome from Genomic Sequencing: A Barrier to Personalized Medicine?" EBioMedicine 2016 Mar ; 5 : 211-6
Abstract

Ackers-Johnson M, Li PY, Holmes AP, O\'Brien SM, Pavlovic D, Foo RS "A Simplified, Langendorff-Free Method for Concomitant Isolation of Viable Cardiac Myocytes and Nonmyocytes From the Adult Mouse Heart." Circ Res 2016 Sep 30 ; 119(8) : 909-20
Abstract

Rachmin I, Amsalem E, Golomb E, Beeri R, Gilon D, Fang P, Nechushtan H, Kay G, Guo M, Yiqing PL, Foo RS, Fisher DE, Razin E, Tshori S "FHL2 switches MITF from activator to repressor of Erbin expression during cardiac hypertrophy." Int J Cardiol 2015 Sep 15 ; 195 : 85-94
Abstract

Pilbrow AP, Cordeddu L, Cameron VA, Frampton CM, Troughton RW, Doughty RN, Whalle y GA, Ellis CJ, Yandle TG, Richards AM, Foo RS "Circulating miR-323-3p and miR-652: candidate markers for the presence and progression of acute coronary syndromes." Int J Cardiol 2014 Sep 20 ; 176(2) : 375-85
Abstract

Rachmin I, Tshori S, Smith Y, Oppenheim A, Marchetto S, Kay G, Foo RS, Dagan N, Golomb E, Gilon D, Borg JP, Razin E "Erbin is a negative modulator of cardiac hypertrophy." Proc Natl Acad Sci U S A 2014 Apr 22 ; 111(16) : 5902-7
Abstract

Siggens L, Figg N, Bennett M, Foo R "Nutrient deprivation regulates DNA damage repair in cardiomyocytes via loss of the base-excision repair enzyme OGG1." FASEB J 2012 May ; 26(5) : 2117-24 Epub 2012 Feb 1
Abstract

Gaspar-Pereira S, Fullard N, Townsend PA, Banks PS, Ellis EL, Fox C, Maxwell AG, Murphy LB, Kirk A, Bauer R, Caamaño JH, Figg N, Foo RS, Mann J, Mann DA, Oakley F "The NF-κB subunit c-Rel stimulates cardiac hypertrophy and fibrosis." Am J Pathol 2012 Mar ; 180(3) : 929-39 Epub 2011 Dec 30
Abstract

Haider S, Cordeddu L, Robinson E, Movassagh M, Siggens L, Vujic A, Choy MK, Goddard M, Lio P, Foo R "The landscape of DNA repeat elements in human heart failure." Genome Biol 2012 Oct 3 ; 13(10) : R90 Epub 2012 Oct 3
Abstract

Movassagh M, Vujic A, Foo R "Genome-wide DNA methylation in human heart failure." Epigenomics 2011 Feb ; 3(1) : 103-9
Abstract

Movassagh M, Choy MK, Knowles DA, Cordeddu L, Haider S, Down T, Siggens L, Vujic A, Simeoni I, Penkett C, Goddard M, Lio P, Bennett MR, Foo RS "Distinct epigenomic features in end-stage failing human hearts." Circulation 2011 Nov 29 ; 124(22) : 2411-22 Epub 2011 Oct 24
Abstract

Choy M, Movassagh M, Foo R "The human variome: genomic and epigenomic diversity." EMBO Mol Med 2011 Oct ; 3(10) : 573-4 Epub 2011 Aug 3
Abstract

Choy MK, Movassagh M, Goh HG, Bennett MR, Down TA, Foo RS "Genome-wide conserved consensus transcription factor binding motifs are hyper-methylated." BMC Genomics 2010 ; 11 : 519 Epub 2010 Sep 27
Abstract

Choy MK, Movassagh M, Siggens L, Vujic A, Goddard M, Sánchez A, Perkins N, Figg N, Bennett M, Carroll J, Foo R "High-throughput sequencing identifies STAT3 as the DNA-associated factor for p53-NF-kappaB-complex-dependent gene expression in human heart failure." Genome Med 2010 ; 2(6) : 37 Epub 2010 Jun 14
Abstract

Movassagh M, Choy MK, Goddard M, Ben nett MR, Down TA, Foo RS "Differential DNA methylation correlates with differential expression of angiogenic factors in human heart failure." PLoS One 2010 ; 5(1) : e8564 Epub 2010 Jan 13
Abstract

Choy MK, Movassagh M, Bennett MR, Foo RS "PKB/Akt activation inhibits p53-mediated HIF1A degradation that is independent of MDM2." J Cell Physiol 2010 Mar ; 222(3) : 635-9
Abstract

Harzheim D, Talasila A, Movassagh M, Foo RS, Figg N, Bootman MD, Roderick HL "Elevated InsP3R expression underlies enhanced calcium fluxes and spontaneous extra-systolic calcium release events in hypertrophic cardiac myocytes." Channels (Austin) 2010 Jan-Feb ; 4(1) : 67-71 Epub 2010 Jan 17
Abstract

Harzheim D, Movassagh M, Foo RS, Ritter O, Tashfeen A, Conway SJ, Bootman MD, Roderick HL "Increased InsP3Rs in the junctional sarcoplasmic reticulum augment Ca2+ transients and arrhythmias associated with cardiac hypertrophy." Proc Natl Acad Sci U S A 2009 Jul 7 ; 106(27) : 11406-11 Epub 2009 Jun 23
Abstract

Movassagh M, Foo RS "Simplified apoptotic cascades." Heart Fail Rev 2008 Jun ; 13(2) : 111-9
Abstract

Foo RS, Nam YJ, Ostreicher MJ, Metzl MD, Whelan RS, Peng CF, Ashton AW, Fu W, Mani K, Chin SF, Provenzano E, Ellis I, Figg N, Pinder S, Bennett MR, Caldas C, Kitsis RN "Regulation of p53 tetramerization and nuclear export by ARC." Proc Natl Acad Sci U S A 2007 Dec 26 ; 104(52) : 20826-31 Epub 2007 Dec 17
Abstract

Foo RS, Chan LK, Kitsis RN, Bennett MR "Ubiquitination and degradation of the anti-apoptotic protein ARC by MDM2." J Biol Chem 2007 Feb 23 ; 282(8) : 5529-35 Epub 2006 Dec 2
Abstract

Nam YJ, Mani K, Wu L, Peng CF, Calvert JW, Foo RS, Krishnamurthy B, Miao W, Ashton AW, Lefer DJ, Kitsis RN "The apoptosis inhibitor ARC undergoes ubiquitin-proteasomal-mediated degradation in response to death stimuli: identification of a degradation-resistant mutant." J Biol Chem 2007 Feb 23 ; 282(8) : 5522-8 Epub 2006 Dec 1
Abstract

Foo RS, Siow RC, Brown MJ, Bennett MR "Heme oxygenase-1 gene transfer inhibits angiotensin II-mediated rat cardiac myocyte apoptosis but not hypertrophy." J Cell Physiol 2006 Oct ; 209(1) : 1-7
Abstract

Foo RS, Mani K, Kitsis RN "Death begets failure in the heart." J Clin Invest 2005 Mar ; 115(3) : 565-71
Abstract