A5014775994- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
- 3D Printing in Biomedical Research
- Neuroscience and Neural Engineering
- Tissue Engineering and Regenerative Medicine
- Cardiomyopathy and Myosin Studies
- COVID-19 and Mental Health
- Cardiac electrophysiology and arrhythmias
- Animal Genetics and Reproduction
- Muscle Physiology and Disorders
- Epigenetics and DNA Methylation
- Congenital heart defects research
- SARS-CoV-2 detection and testing
- Virus-based gene therapy research
- Renal and related cancers
- Cardiac Fibrosis and Remodeling
- Long-Term Effects of COVID-19
- Viral Infections and Immunology Research
- Biomedical Ethics and Regulation
- RNA modifications and cancer
- Receptor Mechanisms and Signaling
- Resilience and Mental Health
- Ion channel regulation and function
- Mitochondrial Function and Pathology
- Reproductive Biology and Fertility
University of Nottingham
2016-2025
Sunny BioDiscovery (United States)
2020-2025
University of Glasgow
2017-2023
Park University
2019-2022
Statistical Service
2022
British Heart Foundation
2022
John Wiley & Sons (United Kingdom)
2022
Interface (United Kingdom)
2022
Czech Academy of Sciences, Biology Centre
2019
University of Lausanne
2019
The polymer polydimethylsiloxane (PDMS) is widely used to build microfluidic devices compatible with cell culture. Whilst convenient in manufacture, PDMS has the disadvantage that it can absorb small molecules such as drugs. In like "Organs-on-Chip", designed examine behavior and test effects of drugs, this might impact drug bioavailability. Here we developed an assay compare absorption a set four cardiac drugs by based on measuring residual non-absorbed compound High Pressure Liquid...
Congenital long QT syndromes (LQTSs) are associated with prolonged ventricular repolarization and sudden cardiac death. Limitations to existing clinical therapeutic management strategies prompted us develop a novel human in vitro drug-evaluation system for LQTS type 2 (LQT2) that will complement the vivo models. Skin fibroblasts from patient KCNH2 G1681A mutation (encodes IKr potassium ion channel) were reprogrammed induced pluripotent stem cells (hiPSCs), which subsequently differentiated...
Cardiomyocytes from human pluripotent stem cells (hPSCs-CMs) could revolutionise biomedicine. Global burden of heart failure will soon reach USD $90bn, while unexpected cardiotoxicity underlies 28% drug withdrawals. Advances in hPSC isolation, Cas9/CRISPR genome engineering and hPSC-CM differentiation have improved patient care, progressed drugs to clinic opened a new era safety pharmacology. Nevertheless, predictive using hPSC-CMs contrasts almost total success. Since this likely relates...
Sarcomeric gene mutations frequently underlie hypertrophic cardiomyopathy (HCM), a prevalent and complex condition leading to left ventricle thickening heart dysfunction. We evaluated isogenic genome-edited human pluripotent stem cell-cardiomyocytes (hPSC-CM) for their validity model, add clarity to, HCM. CRISPR/Cas9 editing produced 11 variants of the HCM-causing mutation c.C9123T-MYH7 [(p.R453C-β-myosin heavy chain (MHC)] in 3 independent hPSC lines. Isogenic sets were differentiated...
Abstract Although all human ESC (hESC) lines have similar morphology, express key pluripotency markers, and can differentiate toward primitive germ layers in vitro, the lineage-specific developmental potential may vary between individual lines. In current study, four hESC were cultured same feeder-free conditions to provide a standardized platform for interline analysis. A high-throughput, forced-aggregation system involving centrifugation of defined numbers hESCs V-96 plates (V-96FA) was...
To realize the full scientific and clinical potential of human embryonic stem cell (hESC)-cardiomyocytes, strategies to overcome high degree heterogeneity differentiated populations are required. Here we demonstrate utility two transgenic approaches in enrichment cardiomyocytes derived from HUES-7 cells: (i) negative selection proliferating cells with herpes simplex virus thymidine kinase/ganciclovir (HSVtk/GCV) suicide gene system; (ii) positive expressing a bicistronic reporter [green...
Widespread provision of human embryonic stem cells (hESCs) for therapeutic use, drug screening and disease modelling will require cell lines sustainable over long periods in culture. Since the short-term, vitro culture mammalian embryos can result DNA methylation changes, epigenetic stability hESCs warrants investigation. Existing hESC have been derived cultured under diverse conditions, providing potential programming differential changes into epigenome that may inter-line variability above...
Large-scale manufacture of human embryonic stem cells (hESCs) is prerequisite to their widespread use in biomedical applications. However, current hESC culture strategies are labor-intensive and employ highly variable processes, presenting challenges for scaled production commercial development. Here we demonstrate that passaging the lines, HUES7, NOTT1, with trypsin feeder-free conditions, compatible complete automation on CompacT SelecT, a commercially available industrially relevant...
AimsLong-QT syndromes (LQTS) are mostly autosomal-dominant congenital disorders associated with a 1:1000 mutation frequency, cardiac arrest, and sudden death. We sought to use cardiomyocytes derived from human-induced pluripotency stem cells (hiPSCs) as an in vitro model develop evaluate gene-based therapeutics for the treatment of LQTS.
Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene (DMD), and characterized progressive weakness skeletal cardiac muscles. Currently, dilated cardiomyopathy due to muscle loss one of major causes lethality late-stage DMD patients. To study molecular mechanisms underlying heart, we generated cardiomyocytes (CMs) from healthy control induced pluripotent stem cells (iPSCs). iPSC-derived CMs (iPSC-CMs) displayed deficiency, as well elevated levels resting Ca(2+),...
Significance Efficient delivery of therapeutic molecules inside cells by nontransgenic approaches is key as gene editing/correction, directed differentiation, and in vivo cell modulation/tracking are translated for regenerative medicine applications. Here we describe a peptide-based system engineered to enhance the activity cell-penetrating peptides achieve exceptional intracellular transduction. Glycosaminoglycan-binding enhanced transduction (GET) uses that interact with membrane heparan...
We aimed to explore university students’ perceptions and experiences of SARS-CoV-2 mass asymptomatic testing, social distancing self-isolation, during the COVID-19 pandemic. This qualitative study comprised four rapid online focus groups conducted at a higher education institution in England, high alert (tier 2) national restrictions. Participants were purposively sampled students (n = 25) representing range gender, age, living circumstances (on/off campus), testing/self-isolation...
This qualitative study explored the impact of COVID-19 self-isolation and social restriction measures on university students, through perspectives both students staff supporting them. The comprised 11 focus groups (students) 26 individual interviews (staff) at a higher education institution in England during period national lockdown (January-March 2021). Participants were (
A scalable and cost-effective synthetic polymer substrate that supports robust expansion subsequent multilineage differentiation of human pluripotent stem cells (hPSCs) with defined commercial media is presented. This can be applied to common cultureware used off-the-shelf after long-term storage. Expansion hPSCs are performed entirely on the polymeric surface, enabling clinical potential hPSC-derived realized.
The ability of materials to define the architecture and microenvironment experienced by cells provides new opportunities direct fate human pluripotent stem (HPSCs) [Robinton DA, Daley GQ (2012) Nature 481(7381):295-305]. However, conditions required for self-renewal vs. differentiation HPSCs are different, a single system that efficiently achieves both outcomes is not available [Giobbe GG, et al. Biotechnol Bioeng 109(12):3119-3132]. We have addressed this dual need developing hydrogel-based...