Roger Sik Yin Foo, M.D
Group Leader
foosyr@gis.a-star.edu.sg
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. Although the disease 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. However whether the genomic stress response is only consequential or exactly which part of it contributes to disease progression remains to be clarified.

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 examine the cause and effect of altered DNA methylation, 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.

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

 

HONORS 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

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