A5042857226- Renal Diseases and Glomerulopathies
- Renal and related cancers
- Single-cell and spatial transcriptomics
- Genetic and Kidney Cyst Diseases
- RNA Research and Splicing
- Lymphatic System and Diseases
- Pediatric Urology and Nephrology Studies
- Genetic Neurodegenerative Diseases
- Chronic Kidney Disease and Diabetes
- Organ Donation and Transplantation
- Renal Transplantation Outcomes and Treatments
- Hyperglycemia and glycemic control in critically ill and hospitalized patients
- Renal and Vascular Pathologies
- Systemic Sclerosis and Related Diseases
- 3D Printing in Biomedical Research
- Cardiovascular Function and Risk Factors
- Nuclear Structure and Function
- Systemic Lupus Erythematosus Research
- Complement system in diseases
- Planarian Biology and Electrostimulation
- Ovarian function and disorders
- Neonatal Respiratory Health Research
- Diabetes Treatment and Management
- Microtubule and mitosis dynamics
- Pancreatic function and diabetes
University College London
2020-2025
Great Ormond Street Hospital
2021-2024
Kidney Care UK
2024
Institute of Child Health
2019
Abstract The development of vascular networks in microfluidic chips is crucial for the long-term culture three-dimensional cell aggregates such as spheroids, organoids, tumoroids, or tissue explants. Despite rapid advancement microvascular network systems and organoid technologies, vascularizing organoids-on-chips remains a challenge engineering. Most existing devices poorly reflect complexity vivo flows require complex technical set-ups. Considering these constraints, we develop platform to...
Therapies targeting blood vessels hold promise for autosomal dominant polycystic kidney disease (ADPKD), the commonest inherited disorder causing failure. However, onset and nature of vascular abnormalities in ADPKD are poorly defined. Accordingly, we employed a combination single-cell transcriptomics, three-dimensional imaging with geometric, topological fractal analyses, multimodal magnetic resonance arterial spin labelling to investigate aberrant microvasculature kidneys. Within human...
ABSTRACT Hallmarks of autosomal dominant polycystic kidney disease (ADPKD), the most common hereditary anomaly, include expanding fluid-filled epithelial cysts, inflammation, and fibrosis. Despite previous work showing potential vascular-based therapies, renal microvascular alterations in ADPKD, their timing, are poorly understood. Using single-cell transcriptomics human microvasculature, we identify a population endothelial cells adjacent to cysts ADPKD. This pericystic endothelium,...
Abstract Cardiotrophin‐1 (CT‐1), a member of the interleukin (IL)‐6 cytokine family, has renoprotective effects in mouse models acute kidney disease and tubulointerstitial fibrosis, but its role glomerular is unknown. To address this, we used model nephrotoxic nephritis to test hypothesis that CT‐1 also protective immune‐mediated disease. Using immunohistochemistry analysis single‐cell RNA‐sequencing data isolated glomeruli, demonstrate expressed glomerulus male mice, predominantly parietal...
Abstract Mutations in the SNX14 gene cause spinocerebellar ataxia, autosomal recessive 20 (SCAR20) both humans and dogs. Studies implicating phenotypic consequences of mutations to be subcellular disruption autophagy lipid metabolism have been limited vitro investigation patient-derived dermal fibroblasts, laboratory engineered cell lines developmental analysis zebrafish morphants. homologues Snz ( Drosophila ) Mdm1 (yeast) also conducted, demonstrated an important biochemical role during...
Abstract WT1 encodes a podocyte transcription factor whose variants can cause an untreatable glomerular disease in early childhood. Although regulates many genes, it is poorly understood which of them are initiators and how they subsequently influence other cell‐types the glomerulus. We hypothesised that this could be resolved using single‐cell RNA sequencing (scRNA‐seq) ligand‐receptor analysis to profile cell–cell communication during stages mice harbouring orthologous human mutation ( Wt1...
Abstract Plasma ultrafiltration in the kidney occurs across glomerular capillaries, which are surrounded by epithelial cells called podocytes. Podocytes have a unique shape maintained complex cytoskeleton, becomes disrupted disease resulting defective filtration and albuminuria. Lack of endogenous thymosin β4 (TB4), an actin sequestering peptide, exacerbates injury disrupts organisation podocyte however, potential exogenous TB4 therapy to improve is unknown. Here, we used Adriamycin (ADR),...
ABSTRACT Studies of the structural and molecular features lymphatic vasculature, which clears fluid, macromolecules leukocytes from tissue microenvironment, have largely relied on animal models, with limited information in human organs beyond traditional immunohistochemical assessment. Here, we use three-dimensional imaging single-cell RNA-sequencing to study lymphatics kidney. We found a hierarchical arrangement vessels within kidneys, initiating along specialised nephron epithelium renal...
Hyperglycaemia is common during acute coronary syndromes (ACS) irrespective of diabetic status and portends excess infarct size mortality, but the mechanisms underlying this effect are poorly understood. We hypothesized that sodium/glucose linked transporter-1 (SGLT1) might contribute to high-glucose ACS examined using an ex-vivo rodent heart model ischaemia-reperfusion injury. Langendorff-perfused rat hearts were subjected 35 min ischemia 2 h reperfusion, with variable glucose reciprocal...
Lymphatic vessels are complex three-dimensional (3D) structures that facilitate tissue fluid clearance and regulate immune responses in health inflammatory contexts. Recent advances wholemount immunolabelling 3D imaging have provided insights into organ-specific heterogeneity of lymphatic structure function. However, the visualisation deep within an intact organ remains a challenge. We hypothesised nanobodies, single-domain antibodies raised camelid species, would result improved labelling...
Abstract Introduction Focal segmental glomerulosclerosis (FSGS) is a significant cause of chronic kidney disease and triggered by podocyte damage which can result in cytoskeletal alterations leading to foot process effacement. Vincristine chemoprotective drug alters microtubules has been used clinically reverse FSGS. However, the mechanisms underlying beneficial effect vincristine are not understood. Methods We exposed immortalised human podocytes serum obtained from an FSGS patient before,...
Abstract Mutations in the SNX14 gene cause spinocerebellar ataxia, autosomal recessive 20 (SCAR20) both humans and dogs. SCAR20 is understood to involve subcellular disruption autophagy lipid metabolism. Previously reported studies on phenotypic consequences of mutations have been limited vitro investigation patient-derived dermal fibroblasts, laboratory engineered cell lines developmental analysis zebrafish morphants. In addition, investigated biochemical roles homologues Snz ( Drosophila )...
Abstract The glomerulus mediates kidney ultrafiltration through specialised epithelial cells called podocytes which line a basement membrane shared with blood capillary endothelium. Cell-cell crosstalk is critical for glomerular function, but its investigation in childhood diseases has received little attention. WT1 encodes transcription factor expressed podocytes, whose heterozygous variants cause devastating disease childhood. We used single-cell RNA sequencing and ligand-receptor...
Abstract Plasma ultrafiltration in the kidney occurs across glomerular capillaries, which are surrounded by epithelial cells called podocytes. Podocytes have a unique shape maintained complex cytoskeleton, becomes disrupted disease resulting defective filtration and albuminuria. Lack of endogenous thymosin β4 (TB4), an actin sequestering peptide, exacerbates injury disrupts organisation podocyte however, effect exogenous TB4 therapy on podocytopathy is unknown. Here, through interrogating...