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All Outputs (57)

Complex Relationship Between Cardiac Fibroblasts and Cardiomyocytes in Health and Disease (2021)
Journal Article
Hall, C., Gehmlich, K., Denning, C., & Pavlovic, D. (2021). Complex Relationship Between Cardiac Fibroblasts and Cardiomyocytes in Health and Disease. Journal of the American Heart Association, 10(5), Article e019338. https://doi.org/10.1161/jaha.120.019338

Cardiac fibroblasts are the primary cell type responsible for deposition of extracellular matrix in the heart, providing support to the contracting myocardium and contributing to a myriad of physiological signaling processes. Despite the importance o... Read More about Complex Relationship Between Cardiac Fibroblasts and Cardiomyocytes in Health and Disease.

Students’ Views Towards SARS-CoV-2 Mass Asymptomatic Testing, Social Distancing and Self-Isolation in a University Setting during the COVID-19 Pandemic: A Qualitative Study (2021)
Working Paper
Blake, H., Knight, H., Jia, R., Corner, J., Morling, J. R., Denning, C., …Vedhara, K. Students’ Views Towards SARS-CoV-2 Mass Asymptomatic Testing, Social Distancing and Self-Isolation in a University Setting during the COVID-19 Pandemic: A Qualitative Study

We aimed to explore university students’ perceptions and experiences of SARS-CoV-2 mass asymptomatic testing, social distancing and self-isolation during the COVID-19 pandemic. This qualitative study comprised of four rapid online focus groups conduc... Read More about Students’ Views Towards SARS-CoV-2 Mass Asymptomatic Testing, Social Distancing and Self-Isolation in a University Setting during the COVID-19 Pandemic: A Qualitative Study.

Discovery of a Novel Polymer for Xeno-Free, Long-Term Culture of Human Pluripotent Stem Cell Expansion (2020)
Journal Article
Nasir, A., Thorpe, J., Burroughs, L., Meurs, J., Pijuan‐Galito, S., Irvine, D. J., …Denning, C. (2020). Discovery of a Novel Polymer for Xeno-Free, Long-Term Culture of Human Pluripotent Stem Cell Expansion. Advanced Healthcare Materials, 10(6), Article 2001448. https://doi.org/10.1002/adhm.202001448

Human pluripotent stem cells (hPSCs) can be expanded and differentiated in vitro into almost any adult tissue cell type, and thus have great potential as a source for cell therapies with biomedical application. In this study, a fully-defined polymer... Read More about Discovery of a Novel Polymer for Xeno-Free, Long-Term Culture of Human Pluripotent Stem Cell Expansion.

Experiences of the COVID-19 pandemic: cross-sectional analysis of risk perceptions and mental health in a student cohort (2020)
Working Paper
Jia, R., Knight, H., Blake, H., Corner, J., Denning, C., Ball, J., …Vedhara, K. Experiences of the COVID-19 pandemic: cross-sectional analysis of risk perceptions and mental health in a student cohort

Objective: This study examined the COVID-19 risk perceptions and mental health of university students on returning to campus in the midst of the COVID-19 pandemic. Methods: An online survey was completed during the first four weeks of the academic... Read More about Experiences of the COVID-19 pandemic: cross-sectional analysis of risk perceptions and mental health in a student cohort.

CRISPR/Cas9-mediated generation and analysis of N terminus polymorphic models of ?2AR in isogenic hPSC-derived cardiomyocytes (2020)
Journal Article
Kondrashov, A., Mohd Yusof, N. A., Hasan, A., Goulding, J., Kodagoda, T., Hoang, D. M., …Denning, C. (2021). CRISPR/Cas9-mediated generation and analysis of N terminus polymorphic models of β2AR in isogenic hPSC-derived cardiomyocytes. Molecular Therapy - Methods and Clinical Development, 20, 39-53. https://doi.org/10.1016/j.omtm.2020.10.019

© 2020 During normal- and patho-physiological situations, the behavior of the beta2-adrenoreceptor (β2AR) is influenced by polymorphic variants. The functional impact of such polymorphisms has been suggested from data derived from genetic association... Read More about CRISPR/Cas9-mediated generation and analysis of N terminus polymorphic models of ?2AR in isogenic hPSC-derived cardiomyocytes.

Transfection of hPSC-Cardiomyocytes Using Viafect™ Transfection Reagent (2020)
Journal Article
Bodbin, S. E., Denning, C., & Mosqueira, D. (2020). Transfection of hPSC-Cardiomyocytes Using Viafect™ Transfection Reagent. Methods and Protocols, 3(3), Article 57. https://doi.org/10.3390/mps3030057

Twenty years since their first derivation, human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have shown promise in disease modelling research, while their potential for cardiac repair is being investigated. However, low transfection effic... Read More about Transfection of hPSC-Cardiomyocytes Using Viafect™ Transfection Reagent.

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., …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., …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., …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., …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.

Multifunctional Bioinstructive 3D Architectures to Modulate Cellular Behavior (2019)
Journal Article
Vaithilingam, J., Sanjuan‐Alberte, P., Campora, S., Rance, G. A., Jiang, L., Thorpe, J., …Rawson, F. J. (2019). Multifunctional Bioinstructive 3D Architectures to Modulate Cellular Behavior. Advanced Functional Materials, 29(38), Article 1902016. https://doi.org/10.1002/adfm.201902016

Biological structures control cell behavior via physical, chemical, electrical, and mechanical cues. Approaches that allow us to build devices that mimic these cues in a combinatorial way are lacking due to there being no suitable instructive materia... Read More about Multifunctional Bioinstructive 3D Architectures to Modulate Cellular Behavior.

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.

Polymer microparticles with defined surface chemistry and topography mediate the formation of stem cell aggregates and cardiomyocyte function (2019)
Journal Article
Alvarez-Paino, M., Amer, M. H., Nasir, A., Cuzzucoli Crucitti, V., Thorpe, J., Burroughs, L., …Rose, F. (2019). Polymer microparticles with defined surface chemistry and topography mediate the formation of stem cell aggregates and cardiomyocyte function. ACS Applied Materials and Interfaces, 11(38), 34560-34574. https://doi.org/10.1021/acsami.9b04769

Surface-functionalized microparticles are relevant to fields spanning engineering and biomedicine, with uses ranging from cell culture to advanced cell delivery. Varying topographies of biomaterial surfaces are also being investigated as mediators of... Read More about Polymer microparticles with defined surface chemistry and topography mediate the formation of stem cell aggregates and cardiomyocyte function.

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., …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., …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.

Simplified footprint-free Cas9/CRISPR editing of cardiac-associated genes in human pluripotent stem cells (2018)
Journal Article
Kondrashov, A., Hoang, M. D., Smith, J. G., Bhagwan, J. R., Duncan, G., Mosqueira, D., …Denning, C. (in press). Simplified footprint-free Cas9/CRISPR editing of cardiac-associated genes in human pluripotent stem cells. Stem Cells and Development, 27(6), https://doi.org/10.1089/scd.2017.0268

Modelling disease with hPSCs is hindered because the impact on cell phenotype from genetic variability between individuals can be greater than from the pathogenic mutation. While ‘footprint-free’ Cas9/CRISPR editing solves this issue, existing approa... Read More about Simplified footprint-free Cas9/CRISPR editing of cardiac-associated genes in human pluripotent stem cells.

MUSCLEMOTION: a versatile open software tool to quantify cardiomyocyte and cardiac muscle contraction in vitro and in vivo (2017)
Journal Article
Sala, L., van Meer, B., Tertoolen, L., Bakkers, J., Bellin, M., Davis, R., …Burton, F. (2018). MUSCLEMOTION: a versatile open software tool to quantify cardiomyocyte and cardiac muscle contraction in vitro and in vivo. Circulation Research, 122(3), e5. https://doi.org/10.1161/CIRCRESAHA.117.312067

Rationale: There are several methods to measure cardiomyocyte (CM) and muscle contraction but these require customized hardware, expensive apparatus and advanced informatics or can only be used in single experimental models. Consequently, data and te... Read More about MUSCLEMOTION: a versatile open software tool to quantify cardiomyocyte and cardiac muscle contraction in vitro and in vivo.