A5038387155- Renal and related cancers
- Genetic and Kidney Cyst Diseases
- Pediatric Urology and Nephrology Studies
- Urological Disorders and Treatments
- Renal Diseases and Glomerulopathies
- Renal cell carcinoma treatment
- Adolescent and Pediatric Healthcare
- Single-cell and spatial transcriptomics
- Lymphatic System and Diseases
- Birth, Development, and Health
- Galectins and Cancer Biology
- Genetic Syndromes and Imprinting
- Chronic Kidney Disease and Diabetes
- Hedgehog Signaling Pathway Studies
- Health and Medical Research Impacts
- Tissue Engineering and Regenerative Medicine
- Adenosine and Purinergic Signaling
- Hypothalamic control of reproductive hormones
- Child and Adolescent Health
- Cellular Mechanics and Interactions
- Vascular Malformations and Hemangiomas
- Biomedical Research and Pathophysiology
- Epigenetics and DNA Methylation
- Cystic Fibrosis Research Advances
- Autopsy Techniques and Outcomes
University College London
2013-2025
Great Ormond Street Hospital
2001-2025
The Royal Free Hospital
2009-2024
Cardiff University
2024
Roland Hill (United Kingdom)
2024
Kidney Care UK
2023-2024
Weatherford College
2015
Institute of Child Health
2010
Institute of Nephro Urology
2007-2009
Hacettepe University
2008
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...
Mutations in hepatocyte nuclear factor 1B (HNF1B), which is a transcription expressed tissues including renal epithelia, associate with abnormal development. While studying phenotypes of children HNF1B mutations, we identified teenager who presented tetany and hypomagnesemia. We retrospectively reviewed radiographic laboratory data for all patients from single center had been screened an mutation. found heterozygous mutations 21 (23%) 91 cases malformation. All mutation carriers fetal...
Renal hypodysplasia (RHD) is characterized by reduced kidney size and/or maldevelopment of the renal tissue following abnormal organogenesis. Mutations in developmental genes have been identified a subset affected individuals. Here, we report first mutations BMP4 and SIX2 patients with RHD. We detected 3 5 RHD patients, different patients. Overexpression assays zebrafish demonstrated that these affect function Bmp4 Six2 vivo. six2.1 bmp4 resulted dorsalization ventralization, respectively,...
Galectin-3 is a β-galactoside binding lectin with roles in diverse processes including proliferation, apoptosis, inflammation and fibrosis which are dependent on different domains of the molecule subcellular distribution. Although galectin-3 known to be upregulated acute kidney injury, relative importance its functions poorly understood underlying pathogenesis. Therefore we experimentally modulated folic acid (FA)-induced injury utilising modified citrus pectin (MCP), derivative can bind...
FSGS is a CKD with heavy proteinuria that eventually progresses to ESRD. Hereditary forms of have been linked mutations in the transient receptor potential cation channel, subfamily C, member 6 ( TRPC6 ) gene encoding nonselective channel. Most these cause gain-of-function phenotype, leading calcium–triggered podocyte cell death, but underlying molecular mechanisms are unclear. We studied effect disease-related using tridimensional silico modeling tetrameric TRPC6. Our results indicated G757...
Kidney cysts can manifest as focal disease (simple and complex kidney cysts), affect a whole (eg, multicystic dysplastic or cystic dysplasia), bilateral autosomal recessive polycystic [ARPKD] dominant [ADPKD]). In children, opposed to adults, larger proportion of are due genetic diseases HNF1B nephropathy, various ciliopathies, tuberous sclerosis complex), fewer patients have simple acquired disease. The purpose this consensus statement is provide clinical guidance on standardization imaging...
Human dysplastic kidneys are developmental aberrations which responsible for many of the very young children with chronic renal failure. They contain poorly differentiated metanephric cells in addition to metaplastic elements. We recently demonstrated that apoptosis was prominent undifferentiated around tubules (Winyard, P.J.D., J. Nauta, D.S. Lirenman, P. Hardman, V.R. Sams, R.A. Risdon, and A.S. Woolf. 1996. Kidney Int. 49:135-146), perhaps explaining tendency some these organs regress. In...
OFD1 is the gene responsible for oral-facial-digital syndrome type 1, a cause of inherited cystic renal disease. The protein contains an N-terminal LisH motif, considered important in microtubule dynamics, and several putative coiled-coil domains. This study used combination microscopic, biochemical, overexpression approaches to demonstrate that core component human centrosome throughout cell cycle. Using series GFP-OFD1 deletion constructs, it was determined N-terminus containing domain not...
Defects of either anosmin-1 or fibroblast growth factor receptor 1 (FGFR1) are known to underlie hereditary Kallmann's syndrome (KS), a human disorder olfactory and gonadotropin-releasing hormone (GnRH) neuronal ontogeny. Here, we report functional interaction between the FGFR1-FGF2-heparan sulfate complex, leading amplified responses in FGFR1 signaling pathway. In embryonic GnRH neuroblasts, wild-type anosmin-1, but not proteins with loss-of-function KS mutations, induces neurite outgrowth...
Human renal adysplasia usually occurs sporadically, and bilateral disease is the most common cause of childhood end-stage failure, a condition that lethal without intervention using dialysis or transplantation. De novo heterozygous mutations in Uroplakin IIIa (UPIIIa) are reported four 17 children with kidney failure caused by absence an overt urinary tract obstruction. One girl one boy unrelated kindreds had missense mutation at CpG dinucleotide cytoplasmic domain UPIIIa (Pro273Leu), both...
Heterogeneity of lymphatic vessels during embryogenesis is critical for organ-specific function. Little known about lymphatics in the developing kidney, despite their established roles pathology mature organ. We performed three-dimensional imaging to characterize vessel formation mammalian embryonic kidney at single-cell resolution. In mouse, we visually and quantitatively assessed development vessels, remodeling from a ring-like anastomosis under nascent renal pelvis; site VEGF-C...
Polycystic kidney diseases (PKD) are genetic disorders characterized by progressive epithelial cyst growth leading to destruction of normally functioning renal tissue. Current therapies have focused on the epithelium, and little is known about how blood lymphatic microvasculature modulates cystogenesis. Hypomorphic Pkd1nl/nl mice were examined, showing that cystogenesis was associated with a disorganized pericystic network vessels expressing platelet/endothelial cell adhesion molecule 1...
Galectin-3 is a beta-galactoside-binding protein with putative roles in development, oncogenesis, and inflammation. Its expression human nephrogenesis has not been previously reported. This study examines galectin-3 early embryos by Western blot immunohistochemistry. 33-kD was detected the apical domain of distal tubules mesonephros also mesonephric duct. In metanephros, adult kidney precursor, domains ureteric bud branches, there intense fetal medullary papillary collecting ducts both...
An intact genome is essential for kidney growth and differentiation, but less known about whether, how, an altered fetal milieu modifies these processes. Maternal low-protein diets perturb of the metanephros, precursor mature kidney. Fetal corticosteroid overexposure may, in part, mediate this, because such downregulate placental 11beta-hydroxysteroid dehydrogenase-2, which degrades maternal corticosteroids. We report that glucocorticoid mineralocorticoid receptors are expressed mouse...
Oral-facial-digital syndrome type 1 (OFD1) is a rare disorder comprising malformations of the face, oral cavity, hands, and feet. Polycystic kidney disease (PKD) more recently recognized feature syndrome.We now report on clinical, radiological histopathological features an OFD1 PKD kindred with five affected members in three subsequent generations.All patients were female had accompanying as assessed by ultrasound scans. The plasma creatinine was normal three, but caused end-stage renal...
Glomerular disease is characterized by morphologic changes in podocyte cells accompanied inflammation and fibrosis. Thymosin β4 regulates cell morphology, inflammation, fibrosis several organs administration of exogenous thymosin improves animal models unilateral ureteral obstruction diabetic nephropathy. However, the role endogenous kidney unknown. We demonstrate that expressed prominently podocytes developing adult mouse glomeruli. Global loss did not affect healthy glomeruli, but...