A5050272598- Pulmonary Hypertension Research and Treatments
- Pluripotent Stem Cells Research
- Mitochondrial Function and Pathology
- Renin-Angiotensin System Studies
- Genomics and Chromatin Dynamics
- Peptidase Inhibition and Analysis
- Endoplasmic Reticulum Stress and Disease
- Tuberculosis Research and Epidemiology
- Gene Regulatory Network Analysis
- Single-cell and spatial transcriptomics
- Pancreatic function and diabetes
- Ubiquitin and proteasome pathways
- DNA and Biological Computing
- Diabetes and associated disorders
- Genomics, phytochemicals, and oxidative stress
- Nanoparticle-Based Drug Delivery
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Metabolism, Diabetes, and Cancer
- RNA regulation and disease
- Vascular Anomalies and Treatments
- Nanoplatforms for cancer theranostics
- Metabolism and Genetic Disorders
- 3D Printing in Biomedical Research
- Diagnosis and treatment of tuberculosis
- Metal-Organic Frameworks: Synthesis and Applications
University of Cambridge
2020-2024
King's College London
2015-2021
British Heart Foundation
2020-2021
German Centre for Cardiovascular Research
2020-2021
Universitätsmedizin Göttingen
2020-2021
Hammersmith Hospital
2016
Imperial College London
2016
The development of nanoparticle (NP)-based drug carriers has presented an exciting opportunity to address challenges in oncology. Among the 100,000 available possibilities, zirconium-based metal–organic frameworks (MOFs) have emerged as promising candidates biomedical applications. Zr-MOFs can be easily synthesized small-size NPs compatible with intravenous injection, whereas ease decorating their external surfaces functional groups allows for targeted treatment. Despite these benefits,...
For monogenic diseases caused by pathogenic loss-of-function DNA variants, attention focuses on dysregulated gene-specific pathways, usually considering molecular subtypes together within causal genes. To better understand phenotypic variability in hereditary hemorrhagic telangiectasia (HHT), we subcategorized variants ENG/endoglin, ACVRL1/ALK1, and SMAD4 if they generated premature termination codons (PTCs) subject to nonsense-mediated decay. In 3 patient cohorts, a PTC-based classification...
Pulmonary arterial hypertension (PAH) is a disorder with large genetic component. Biallelic mutations of EIF2AK4, which encodes the kinase GCN2, are causal in two ultra-rare subtypes PAH, pulmonary veno-occlusive disease and capillary haemangiomatosis. EIF2AK4 variants unknown significance have also been identified patients classical though their relationship to remains unclear. To provide diagnostic information enable family testing, functional consequences such rare must be determined, but...
In response to cardiac injury, increased activity of the hexosamine biosynthesis pathway (HBP) is linked with cytoprotective as well adverse effects depending on type and duration injury. Glutamine-fructose amidotransferase (GFAT; gene name gfpt) rate-limiting enzyme that controls flux through HBP. Two protein isoforms exist in heart called GFAT1 GFAT2. There are conflicting data relative importance GFAT2 during stress-induced HBP responses heart. Using neonatal rat cell preparations,...
Abstract Pulmonary arterial hypertension (PAH) is a disorder with large genetic component. Biallelic mutations of EIF2AK4 , which encodes the kinase GCN2, are causal in two ultra-rare subtypes PAH, pulmonary veno-occlusive disease and capillary haemangiomatosis. variants unknown significance have also been identified patients classical though their relationship to remains unclear. To provide diagnostic information enable family testing, functional consequences such rare must be determined,...
Heterochromatinisation of pericentromeres, which in mice consist arrays major satellite repeats, are important for centromere formation and maintenance genome stability. The dysregulation this process has been linked to genomic stress various cancers. Here we show that the proteasome binds repeats inhibition by MG132 results their transcriptional de-repression; de-repression is independent cell-cycle perturbation. activation upon accompanied delocalisation heterochromatin protein 1 alpha...
Abstract Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are an increasingly employed model in cardiac research and drug discovery. A significant limitation with respect to clinical translation is their immature structural functional phenotype. Cellular metabolism plays integral role determining phenotype but the metabolic profile of hiPSC-CM during maturation poorly characterized. In this study we employ a combination methods including extracellular flux 13 C-glucose...
<h3></h3> Pulmonary arterial hypertension (PAH) is a fatal condition affecting young adults in which aberrant pulmonary vascular remodelling raises artery pressures causing right heart failure. It frequently caused by mutations of the type II BMP receptor (BMPR2), however additional modifying factors exist. Mutations <i>EIF2AK4</i> gene, encoding kinase GCN2 have also been associated with PAH but mechanisms remain elusive. In healthy individuals, active selectively phosphorylates eIF2α to...