MOMMENTUM-CVD

NMRC centre Grant
Molecular Markers, MEchaNisms and their TherapeUtic Manipulation
in CardioVascular Disease
Gel electrophoresis under UV light​

Implementation science translates research discoveries into healthcare policy and practice. Singapore has the core infrastructure enabling a learning healthcare system to address big-data questions, evaluate internet-of-things (IoT), healthcare solutions and support large-scale pragmatic trials. Successful integration of large data sets can address key questions in healthcare policy. We worked with colleagues from the National Heart Centre Singapore (NHCS), National Registry of Diseases Office (NRDO), and Ministry of Health (MOH) to link 3 independent datasets (Singapore Cardiac Databank CathPCI database, Singapore Myocardial Infarct Registry and MOH OMNIBUS) to demonstrate that temporal improvements in reperfusion time for ST-elevation myocardial infarction (STEMI) were associated with a lower incidence of post-myocardial Infarction Heart Failure.

MOMMENTUM-CVD consists of 4 cores:

TEAM
Roger Foo, Chester Drum, Jiang Jianming, Roshni Singaraja, Mark Chan, Koh Cho Yeow, Matthew Ackers-Johnson, Wong Lee Lee, Vitaly A. Sorokin, Wang JiongWei, Arthur Mark Richards, Wang Peipei

SCOPE
Molecular Discovery will expand our strength in epigenetics and biomarkers encompassing-omics technologies, including non-coding RNA studies, genomics, peptide immunoassay and proteomic screening platforms to discover and validate new molecular targets with marker and therapeutic potential.

Platforms supported by Core 1 include:

Genomic / epigenetic discovery
Analysis of DNA, chromatin and RNA from multiple sources in both clinical and experimental pre-clinical settings. DNA sequencing via a custom-built NGS inherited cardiac gene panel (applied to SG10K and ATTRACT genomes). For RNA and epigenomes we deploy RNAseq, single-cell transcriptomics, assessment of histone modifications, chromatin interactomes, HiC, and perform transcription factor ChIPseq. Data are stored in computing clusters at GIS and the National Super Computer Centre. Capabilities through this Centre contribute strategically to developing bioinformatics expertise among clinician-scientists on the NUHS campus within and beyond CVRI.

Circulating biomarker discovery and assay development
Technologies include, immunoassay, PCR and mass spectrometry. Since 2009, CVRI has bio-banked samples from annotated clinical cohorts (>20,000 participants recruited nationwide) spanning coronary disease, heart failure, atrial fibrillation, and valve disease – totalling >200,000 individual aliquots of DNA, PBMCs, EDTA, heparin and citrate anticoagulated plasma. The department of cardiothoracic and vascular surgery tissue repository has 16,820 samples of aorta, peripheral artery, veins, myocardium and cardiac valves. Methods include standard ELISA, multiplex bead-based assay, FRET-based assay and proximity-extension assay platforms. Equipment includes automated immunoanalysers (Abbott Architect i2000SR and Roche Cobas e411 analysers), Bio-PlexÒ Multi-Suspension Array System, ELLA (“Next Generation” ELISAs on single or multiplex microfluidic cartridges) and the EnspireÒ Multi-Mode Plate Reader with access to the BioMark™ System (Fluidigm). The Richards’ group develops in-house immunoassays via targeted cloning of epitope-directed monoclonal antibodies characterized (isotyping, surface plasmon resonance-based affinity, epitope mapping and mass spectroscopy) and validated for ELISA, Western blotting and immunohistochemistry.

The Mass Spectrometry Laboratory
Runs 3 highly sensitive Agilent 6495 triple-quadrupole (QqQ) MS machines and the Agilent Ultivo QqQ MS. MS-targeted metabolomics profiling methods detect over 400 endogenous small molecule metabolites including (i) a comprehensive panel of oxidative stress markers, (ii) components of multiple metabolic pathways (iii) NAD metabolome/electron transport chain, (iv) amino acids (v) drugs and (vi) deoxyguanosine (DNA damage) and 8-Hydroxyguanine (RNA damage).