FOO LAB

Impactful scientific discoveries through world-class research
Epigenomics and regulation
The basic science of how gene regulation works keeps evolving as technologies sharpen. We adopt and exploit advances in technologies to push forward our understanding of regulation and heart biology and disease.


Personalized medicine
Cardiac Epigenomics
Personalized medicine, it's coming
Epigenomics
We found that as much as gene expression and epigenomic signals change in disease, they also vary from individual to individual.
Genetic variants
Cardiac traits are influenced by genetic variants. Phenotypic refinement and collecting genetic diversity is helping us to learn more about human heart failure pathways. We are exploring south-east Asian genetic backgrounds which are understudied and susceptible to disease.
Massively parralel reporter assays
We are implementing and adopting MPRA technologies and machine learning to help identify regulatory genetic variants that influence individual risk of heart failure and targetable human genes.
In future medicine and clinical practice should be optimized for each patient.

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*Tan, K., Foo, R., & Loh, M. (2023). Cardiomyopathy in Asian Cohorts: Genetic and Epigenetic Insights. Circ Genom Precis Med, 16(5), 496-506. doi:10.1161/CIRCGEN.123.004079 (JIF: 7.46)
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Gomes, B., Singh, A., O'Sullivan, J. W., Schnurr, T. M., Goddard, P. C., Loong, S., . . . Ashley, E. A. (n.d.). Genetic architecture of cardiac dynamic flow volumes. Nat Genet, 20 pages. doi:10.1038/s41588-023-01587-5 (JIF: 41.3)
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Chan, S. H., Bylstra, Y., Teo, J. X., Kuan, J. L., Bertin, N., Gonzalez-Porta, M., . . . Lim, W. K. (2022). Analysis of clinically relevant variants from ancestrally diverse Asian genomes. Nat Commun, 13(1), 15 pages. doi:10.1038/s41467-022-34116-9 (JIF: 17.69)
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Tomar, S., Klinzing, D. C., Kit, C. C., Gan, L. H., Moscarello, T., Reuter, C., . . . Foo, R. (2022). Causative Variants for Inherited Cardiac Conditions in a Southeast Asian Population Cohort. Circ Genom Precis Med, 15(2), 100-109. doi:10.1161/CIRCGEN.121.003536 (JIF: 7.46)
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Zhou, J., Azizan, E. A. B., Cabrera, C. P., Fernandes-Rosa, F. L., Boulkroun, S., Argentesi, G., . . . Brown, M. J. (2021). Somatic mutations of GNA11 and GNAQ in CTNNB1-mutant aldosterone-producing adenomas presenting in puberty, pregnancy or menopause. Nat Genet, 53(9), 1360-+. doi:10.1038/s41588-021-00906-y (JIF: 41.30)
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Wu, D., Dou, J., Chai, X., Bellis, C., Wilm, A., Shih, C. C., . . . Wang, C. (2019). Large-Scale Whole-Genome Sequencing of Three Diverse Asian Populations in Singapore. Cell, 179(3), 736-+. doi:10.1016/j.cell.2019.09.019 (JIF: 66.85)

Dedifferentiation
We are researching dedifferentiation as it applies to the heart.
Can reprogramming cardiomyocytes reverse aging? Or support cardiomyocyte function and heart repair in diseased states?
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Transdifferentiation and dedifferentiation studies have got Foo Lab excited that functional epigenomics approaches might help us to fight heart failure one day soon.
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Zhu Y, Ackers-Johnson M, Shanmugam MK, Pakkiri LS, Drum CL, Chen Y, Kim J, Paltzer WG, Mahmoud AI, Tan WLW, Lee MCJ, Jiang J, Luu DAT, Ng SL, Li PYQ, Wang A, Qi R, Ong GJX, Ng TY, Haigh JJ, Tiang Z, Richards AM, Foo RSY. (2024). Asparagine synthetase marks a dependency threshold for cardiomyocyte dedifferentiation. Circulation 149(23):1833-1851. doi: 10.1161/CIRCULATIONAHA.123.063965. (JIF: 39.92)
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Lee CJM, Autio MI, Zheng WH, Song Y, Wang SC, Wong DCP, Xiao J, Zhu Y, Yusoff P, Yei X, Chock WK, Low BC, Sudol M, Foo RS. (2024). Genome-Wide CRISPR Screen Identifies an NF2-Adherens Junction Mechanistic Dependency for Cardiac Lineage. Circulation May 16. doi: 10.1161/CIRCULATIONAHA.122.061335. Online ahead of print. (JIF: 39.92)
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*Zhu, Y., Do, V. D., Richards, A. M., & Foo, R. (2021). What we know about cardiomyocyte dedifferentiation. J Mol Cell Cardiol, 152, 80-91. doi:10.1016/j.yjmcc.2020.11.016 (JIF: 5.76)
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Tan, W. L. W., Lim, B. T. S., Anene-Nzelu, C. G. O., Ackers-Johnson, M., Dashi, A., See, K., . . . Foo, R. S. Y. (2017). A landscape of circular RNA expression in the human heart. Cardiovasc Res, 113(3), 298-309. doi:10.1093/cvr/cvw250 (JIF: 13.08)

haQTL, GWAS, epigenomes
Multiple labs including ours have shown that genetic variants influence expression of genes in the heart and related tissues and these variants influence disease risk

More work needs doing to go from these early clues to established pathways and treatments and interventions. For example GWAS variants need to be associated to enhancers or promoters, validated and those genes need characterizing to elucidate the role in disease.
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*Anene-Nzelu, C. G., Lee, M. C. J., Tan, W. L. W., Dashi, A., & Foo, R. S. Y. (2022). Genomic enhancers in cardiac development and disease. Nat Rev Cardiol, 19(1), 7-25. doi:10.1038/s41569-021-00597-2 (JIF: 49.42)
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Hawe, J. S., Wilson, R., Schmid, K. T., Zhou, L., Lakshmanan, L. N., Lehne, B. C., . . . Chambers, J. C. (2022). Genetic variation influencing DNA methylation provides insights into molecular mechanisms regulating genomic function. Nat Genet, 54(1), 18-+. doi:10.1038/s41588-021-00969-x (JIF: 41.30)
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Madsen, A., Hoppner, G., Krause, J., Hirt, M. N., Laufer, S. D., Schweizer, M., . . . Stenzig, J. (2021). An Important Role for DNMT3A-Mediated DNA Methylation in Cardiomyocyte Metabolism and Contractility Circulation, 143(15), E830. doi:10.1161/CIR.0000000000000978 (JIF: 39.92)
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Madsen, A., Hoeppner, G., Krause, J., Hirt, M. N., Laufer, S. D., Schweizer, M., . . . Stenzig, J. (2020). An Important Role for DNMT3A-Mediated DNA Methylation in Cardiomyocyte Metabolism and Contractility. Circulation, 142(16), 1562-1578. doi:10.1161/CIRCULATIONAHA.119.044444 (JIF: 39.92)
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Anene-Nzelu, C. G., Tan, W. L. W., Lee, C. J. M., Wenhao, Z., Perrin, A., Dashi, A., . . . Foo, R. S. -Y. (2020). Assigning Distal Genomic Enhancers to Cardiac Disease-Causing Genes. Circulation, 142(9), 910-912. doi:10.1161/CIRCULATIONAHA.120.046040 (JIF: 39.92)
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Tan, W. L. W., Anene-Nzelu, C. G., Wong, E., Lee, C. J. M., Tan, H. S., Tang, S. J., . . . Foo, R. S. Y. (2020). Epigenomes of Human Hearts Reveal New Genetic Variants Relevant for Cardiac Disease and Phenotype. Circ Res, 127(6), 761-777. doi:10.1161/CIRCRESAHA.120.317254 (JIF: 23.21)
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Foo, R. S. -Y., Anene-Nzelu, C. G., Rosa-Garrido, M., & Vondriska, T. M. (2019). Dissecting Chromatin Architecture for Novel Cardiovascular Disease Targets. Circulation, 140(6), 446-448. doi:10.1161/CIRCULATIONAHA.119.039287 (JIF: 39.92)
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Ackers-Johnson, M., Tan, W. L. W., & Foo, R. S. -Y. (2018). Following hearts, one cell at a time: recent applications of single-cell RNA sequencing to the understanding of heart disease. Nat Commun, 9, 4 pages. doi:10.1038/s41467-018-06894-8 (JIF: 17.69)
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Jonsson, M. K. B., Hartman, R. J. G., Ackers-Johnson, M., Tan, W. L. W., Lim, B., van Veen, T. A. B., & Foo, R. S. (2016). A Transcriptomic and Epigenomic Comparison of Fetal and Adult Human Cardiac Fibroblasts Reveals Novel Key Transcription Factors in Adult Cardiac Fibroblasts. JACC: Basic Transl Sci, 1(7), 590-602. doi:10.1016/j.jacbts.2016.07.007 (JIF: 9.7)
