Outputs (40)

Mitochondrial DNA: Hotspot for Potential Gene Modifiers Regulating Hypertrophic Cardiomyopathy (2020)
Journal Article
Kargaran, P. K., Evans, J. M., Bodbin, S. E., Smith, J. G. W., Nelson, T. J., Denning, C., & Mosqueira, D. (2020). Mitochondrial DNA: Hotspot for Potential Gene Modifiers Regulating Hypertrophic Cardiomyopathy. Journal of Clinical Medicine, 9(8), Article 2349. https://doi.org/10.3390/jcm9082349

Hypertrophic cardiomyopathy (HCM) is a prevalent and untreatable cardiovascular disease with a highly complex clinical and genetic causation. HCM patients bearing similar sarcomeric mutations display variable clinical outcomes, implying the involveme... Read More about Mitochondrial DNA: Hotspot for Potential Gene Modifiers Regulating Hypertrophic Cardiomyopathy.

Blinded, multi-centre evaluation of drug-induced changes in contractility using human induced pluripotent stem cell-derived cardiomyocytes (2020)
Journal Article
Saleem, U., van Meer, B. J., Katili, P. A., Yusof, N. A. N. M., Mannhardt, I., Garcia, A. K., Tertoolen, L., de Korte, T., Vlaming, M. L., McGlynn, K., Nebel, J., Bahinski, A., Harris, K., Rossman, E., Xu, X., Burton, F. L., Smith, G. L., Clements, P., Mummery, C. L., Eschenhagen, T., …Denning, C. (2020). Blinded, multi-centre evaluation of drug-induced changes in contractility using human induced pluripotent stem cell-derived cardiomyocytes. Toxicological Sciences, 176(1), 103–123. https://doi.org/10.1093/toxsci/kfaa058

Animal models are 78% accurate in determining whether drugs will alter contractility of the human heart. To evaluate the suitability of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) for predictive safety pharmacology, we quan... Read More about Blinded, multi-centre evaluation of drug-induced changes in contractility using human induced pluripotent stem cell-derived cardiomyocytes.

N6-methyladenosine regulates the stability of RNA:DNA hybrids in human cells (2019)
Journal Article
Abakir, A., Giles, T. C., Cristini, A., Foster, J. M., Dai, N., Starczak, M., Rubio-Roldan, A., Li, M., Eleftheriou, M., Crutchley, J., Flatt, L., Young, L., Gaffney, D. J., Denning, C., Dalhus, B., Emes, R. D., Gackowski, D., Corrêa, I. R., Garcia-Perez, J. L., Klungland, A., …Ruzov, A. (2020). N6-methyladenosine regulates the stability of RNA:DNA hybrids in human cells. Nature Genetics, 52(1), 48-55. https://doi.org/10.1038/s41588-019-0549-x

© 2019, The Author(s), under exclusive licence to Springer Nature America, Inc. R-loops are nucleic acid structures formed by an RNA:DNA hybrid and unpaired single-stranded DNA that represent a source of genomic instability in mammalian cells1–4. Her... Read More about N6-methyladenosine regulates the stability of RNA:DNA hybrids in human cells.

Variable expression and silencing of CRISPR-Cas9 targeted transgenes identifies the AAVS1 locus as not an entirely safe harbour (2019)
Journal Article
Bhagwan, J. R., Collins, E., Mosqueira, D., Bakar, M., Johnson, B. B., Thompson, A., Smith, J. G., & Denning, C. (in press). Variable expression and silencing of CRISPR-Cas9 targeted transgenes identifies the AAVS1 locus as not an entirely safe harbour. F1000Research, 8, Article 1911. https://doi.org/10.12688/f1000research.19894.1

Background: Diseases such as hypertrophic cardiomyopathy (HCM) can lead to severe outcomes including sudden death. The generation of human induced pluripotent stem cell (hiPSC) reporter lines can be useful for disease modelling and drug screening by... Read More about Variable expression and silencing of CRISPR-Cas9 targeted transgenes identifies the AAVS1 locus as not an entirely safe harbour.

High-Throughput Phenotyping Toolkit for Characterizing Cellular Models of Hypertrophic Cardiomyopathy in Vitro (2019)
Journal Article
Mosqueira, D., Lis-Slimak, K., & Denning, C. (2019). High-Throughput Phenotyping Toolkit for Characterizing Cellular Models of Hypertrophic Cardiomyopathy in Vitro. Methods and Protocols, 2(4), 1-26. https://doi.org/10.3390/mps2040083

Hypertrophic cardiomyopathy (HCM) is a prevalent and complex cardiovascular disease characterised by multifarious hallmarks, a heterogeneous set of clinical manifestations, and several molecular mechanisms. Various disease models have been developed... Read More about High-Throughput Phenotyping Toolkit for Characterizing Cellular Models of Hypertrophic Cardiomyopathy in Vitro.

Simultaneous measurement of excitation-contraction coupling parameters identifies mechanisms underlying contractile responses of hiPSC-derived cardiomyocytes (2019)
Journal Article
Van Meer, B. J., Krotenberg, A., Sala, L., Davis, R. P., Eschenhagen, T., Denning, C., Tertoolen, L. G. J., & Mummery, C. L. (2019). Simultaneous measurement of excitation-contraction coupling parameters identifies mechanisms underlying contractile responses of hiPSC-derived cardiomyocytes. Nature Communications, 10, Article 4325. https://doi.org/10.1038/s41467-019-12354-8

Cardiomyocytes from human induced pluripotent stem cells (hiPSC-CMs) are increasingly recognized as valuable for determining the effects of drugs on ion channels but they do not always accurately predict contractile responses of the human heart. This... Read More about Simultaneous measurement of excitation-contraction coupling parameters identifies mechanisms underlying contractile responses of hiPSC-derived cardiomyocytes.

Modeling Hypertrophic Cardiomyopathy: Mechanistic Insights and Pharmacological Intervention (2019)
Journal Article
Bhagwan, J. R., Smith, J. G., Mosqueira, D., Smith, J. G. W., Bhagwan, J. R., & Denning, C. (2019). Modeling Hypertrophic Cardiomyopathy: Mechanistic Insights and Pharmacological Intervention. Trends in Molecular Medicine, 25(9), 775-790. https://doi.org/10.1016/j.molmed.2019.06.005

HCM is a prevalent and complex disease governed by multiple molecular mechanisms, and there is currently no efficient cure. New treatment strategies are under development, and several drugs are reaching the final stages of clinical trials, with parti... Read More about Modeling Hypertrophic Cardiomyopathy: Mechanistic Insights and Pharmacological Intervention.

Surface plasmon resonance imaging of excitable cells (2019)
Journal Article
Howe, C. L., Webb, K. F., Abayzeed, S. A., Anderson, D. J., Denning, C., & Russell, N. A. (2019). Surface plasmon resonance imaging of excitable cells. Journal of Physics D: Applied Physics, 52(10), Article 104001. https://doi.org/10.1088/1361-6463/aaf849

Surface plasmons (SPs) are surface charge density oscillations occuring at a metal/dieletric interface and are highly sensitive to refractive index variations adjacent to the surface. This sensitivity has been exploited successfully for chemical and... Read More about Surface plasmon resonance imaging of excitable cells.

Isogenic pairs of hiPSC-CMs with hypertrophic cardiomyopathy/LVNC-associated ACTC1 E99K mutation unveil differential functional deficits (2018)
Journal Article
Smith, J. G., Owen, T., Bhagwan, J. R., Mosqueira, D., Scott, E., Mannhardt, I., Patel, A., Barriales-Villa, R., Monserrat, L., Hansen, A., Eschenhagen, T., Harding, S. E., Marston, S., & Denning, C. (2018). Isogenic pairs of hiPSC-CMs with hypertrophic cardiomyopathy/LVNC-associated ACTC1 E99K mutation unveil differential functional deficits. Stem Cell Reports, 11(5), 1226-1243. https://doi.org/10.1016/j.stemcr.2018.10.006

Hypertrophic cardiomyopathy (HCM) is a primary disorder of contractility in heart muscle. To gain mechanistic insight and guide pharmacological rescue, this study models HCM using isogenic pairs of hiPSC-CMs carrying the E99K-ACTC1 cardiac actin mut... Read More about Isogenic pairs of hiPSC-CMs with hypertrophic cardiomyopathy/LVNC-associated ACTC1 E99K mutation unveil differential functional deficits.

CRISPR/Cas9 editing in human pluripotent stem cell-cardiomyocytes highlights arrhythmias, hypocontractility, and energy depletion as potential therapeutic targets for hypertrophic cardiomyopathy (2018)
Journal Article
Mosqueira, D., Mannhardt, I., Bhagwan, J. R., Lis-Slimak, K., Katili, P., Scott, E., Hassan, M., Prondzynski, M., Harmer, S. C., Tinker, A., Smith, J. G., Carrier, L., Williams, P. M., Gaffney, D., Eschenhagen, T., Hansen, A., & Denning, C. (2018). CRISPR/Cas9 editing in human pluripotent stem cell-cardiomyocytes highlights arrhythmias, hypocontractility, and energy depletion as potential therapeutic targets for hypertrophic cardiomyopathy. European Heart Journal, 39(43), 3879-3892. https://doi.org/10.1093/eurheartj/ehy249

Aims: Sarcomeric gene mutations frequently underlie hypertrophic cardiomyopathy (HCM), a prevalent and complex condition leading to left ventricle thickening and heart dysfunction. We evaluated isogenic genome-edited human pluripotent stem cell-cardi... Read More about CRISPR/Cas9 editing in human pluripotent stem cell-cardiomyocytes highlights arrhythmias, hypocontractility, and energy depletion as potential therapeutic targets for hypertrophic cardiomyopathy.