{"id":1294,"date":"2023-07-14T14:40:02","date_gmt":"2023-07-14T06:40:02","guid":{"rendered":"https:\/\/medicine.nus.edu.sg\/trp\/cardiovascular-disease\/?page_id=1294"},"modified":"2023-11-06T19:27:35","modified_gmt":"2023-11-06T11:27:35","slug":"mommentum-cvd","status":"publish","type":"page","link":"https:\/\/medicine.nus.edu.sg\/trp\/cardiovascular-disease\/flagship-projects\/mommentum-cvd\/","title":{"rendered":"MOMMENTUM-CVD"},"content":{"rendered":"\t\t
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MOMMENTUM-CVD<\/h1>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t
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Molecular Markers, MEchaNisms and their TherapeUtic Manipulation
in CardioVascular Disease<\/h5>\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t
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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.<\/p>

MOMMENTUM-CVD consists of 4 cores:<\/p>\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t<\/div>\n\t\t\t\t

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

SCOPE
<\/strong>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.<\/p>

Platforms supported by Core 1 include:
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Genomic \/ epigenetic discovery<\/strong>
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.<\/p>

Circulating biomarker discovery and assay development<\/strong>
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 \u2013 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-Plex\u00d2 Multi-Suspension Array System, ELLA (\u201cNext Generation\u201d ELISAs on single or multiplex microfluidic cartridges) and the Enspire\u00d2 Multi-Mode Plate Reader with access to the BioMark\u2122 System (Fluidigm). The Richards\u2019 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.<\/p>

The Mass Spectrometry Laboratory<\/strong>
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).<\/p>

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Team<\/h6>

Mark Chan<\/a>,\u202fRonald Lee Chi Hang<\/a>, Lim Shir Lynn<\/a>, Vitaly A. Sorokin<\/a>, Ling Lieng Hsi<\/a>, Chester Drum<\/a>, Arthur Mark Richards<\/a>, Andrew Mark Choong Tze Liang<\/p>

Scope<\/h6>

Clinical Science will underpin and expand our clinical links facilitating the acquisition of biological samples and accelerating our participation in early (Phase 2) clinical trials.<\/p>

Clinical Trails<\/h6>

Clinical Trials\u202finfrastructure (Clinical Trial Coordinators, space, Ethics, documentation) is overseen by Dr Lim Shir Lynn with input from clinical investigators. The Cardiovascular Clinical Trials Unit employs 12 full-time CRCs supporting investigator-initiated and industry-supported studies. The unit has a physical space and an electronic platform for secure data storage.<\/p>

Cardiovascular Imaging Core Laboratory<\/h6>

The Cardiovascular Imaging Core Laboratory (CICL; Assoc Prof Ling Lieng Hsi, Dr Lynette Teo) at NUHCS is Singapore\u2019s core echocardiography and vascular imaging laboratory providing state-of-the-art cardiac ultrasound and vascular phenotyping (atherosclerosis, regional, arterial stiffness, vascular reactivity, skin autofluoresence for advanced glycation end-products) in 3 dedicated imaging suites. Data are archived on a GE-based server system (pending an upgrade to the ViewPoint platform). CICL serves as the core ultrasound laboratory for both NUHCS CG and the Collaborative CG held with our partner heart centre, NHCS.<\/p>

Complementing CICL, our access to 4 ultrafast CT and 6 MRI machines, MR-PET and MR-SPECT in NUH\/NUS facilities, positions us well for high throughput in imaging cohort studies and clinical trials.<\/p>

Computational fluid dynamics<\/h6>

Vascular Computational fluid dynamics overseen by Dr Andrew Choong.<\/p>

Cardiosleep Laboratory<\/h6>

PI: Prof Ronald Lee<\/strong>
The cardiosleep lab runs trials including (1) CRESCENT \u2013 multicentre, randomized comparison of CPAP vs mandibular advancement device (MAD) (2) POACH \u2013 determining the CV effects of OSA in atrial fibrillation (3) SAGIC-CVD \u2013 multi-national propensity scored trial to evaluate the impact of CPAP therapy on BP in the excessive sleepiness phenotype, (4) MANTA -a collaboration with University of Sydney trialling a novel MAD in atrial fibrillation (5) Belun Ring study- a collaboration with a commercial start-up to validate a novel sleep monitoring device (6) Drug-induced sleep endoscopy (DISE) \u2013 a collaboration with otolaryngologists to characterize anatomical patterns of upper airway obstruction using drug-induced sleep endoscopy.<\/p><\/div>\n\t\t\t\t<\/div>\n\t\t\t\t\t\t\t

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Team<\/h6>

Theodoros Kofidis<\/a>,\u202fRoshni Rebecca Singaraja<\/a>,\u202fRoger Foo<\/a>, Wong Lee Lee<\/a>, Mark Chan<\/a>, Koh Cho Yeow<\/a>, Matthew Ackers-Johnson<\/a>, Wang Jiongwei<\/a>, Arthur Mark Richards<\/a>, Wang Pei Pei<\/p>

Scope\u00a0<\/h6>

Preclinical Modelling will support the array of\u202fin vitro,\u202fex vivo\u202fand\u202fin vivo\u202fcell and animal models underpinning our basic research efforts including the following platform.<\/p>

Capabilities<\/h6>

The in vitro modelling platform<\/strong> for (1) primary vascular tissues (Singaraja), (2) iPS-derived human vascular tissues (Ackers-Johnson) and (3) 3D-organoid models of vessels (Sorokin) supports to validate selected targets. Dissociated vascular tissue will be used to acquire primary patient-specific VSMCs and Endothelial cells to create organoids. PBMC-derived M0 macrophages will be added into 3D organoids to elaborate vascular tissue-immune cell interactions relevant to atherogenesis. PBMC-derived iPS cells are generated for comparison of blood-acquired vs tissue-originated organoids. iPSC-derived organoids will provide patient-derived 3D organoids for downstream target validation.<\/p>