A5033126354- Genetic and Kidney Cyst Diseases
- Congenital heart defects research
- Renal and related cancers
- Hedgehog Signaling Pathway Studies
- Muscle Physiology and Disorders
- Developmental Biology and Gene Regulation
- Epigenetics and DNA Methylation
- Cardiomyopathy and Myosin Studies
- Connective tissue disorders research
- Birth, Development, and Health
- Genetic Syndromes and Imprinting
- Cellular transport and secretion
- Protein Tyrosine Phosphatases
- Ubiquitin and proteasome pathways
- Hereditary Neurological Disorders
- Pancreatic function and diabetes
- Neurogenetic and Muscular Disorders Research
- Endoplasmic Reticulum Stress and Disease
- Renin-Angiotensin System Studies
- Complement system in diseases
- Neurological diseases and metabolism
- Cellular Mechanics and Interactions
- Immune Cell Function and Interaction
- Wnt/β-catenin signaling in development and cancer
- Urological Disorders and Treatments
St George's, University of London
2014-2024
Institut thématique Génétique, génomique et bioinformatique
2022
King's College London
2006-2020
University College London
2009-2014
Institute of Child Health
2011
Centrioles are the foundation for centrosome and cilia formation. The biogenesis of centrioles is initiated by an assembly mechanism that first synthesizes ninefold symmetrical cartwheel subsequently leads to a stable cylindrical microtubule scaffold capable withstanding microtubule-based forces generated centrosomes cilia. We report conserved WD40 repeat domain–containing protein Poc1 required structural maintenance in Tetrahymena thermophila. Furthermore, human Poc1B primary ciliogenesis,...
Myogenic regulatory factors of the Myod family (MRFs) are transcription essential for mammalian skeletal myogenesis. However,the roles each gene in myogenesis remain unclear, owing partly to genetic linkage at Myf5/Mrf4 locus and rapid morphogenetic movements amniote somite. In mice, Myf5 is earliest epaxial myogenesis, whereas required timely differentiation hypaxially derived muscle. A second major subdivision somite between primaxial muscle proper abaxial somite-derived migratory...
Primary cilia are involved in important developmental and disease pathways, such as regulation of neurogenesis tumorigenesis. They function sensory antennae essential the key extracellular signalling systems. Here we investigate effects cell stress on primary cilia. Exposure mammalian cells vitro, zebrafish vivo, to elevated temperature resulted rapid loss by resorption. In correlated with a reduction hedgehog signalling. Heat shock dependent was decreased where histone deacetylases (HDACs)...
Article20 December 2017Open Access Source DataTransparent process WDR11-mediated Hedgehog signalling defects underlie a new ciliopathy related to Kallmann syndrome Yeon-Joo Kim orcid.org/0000-0001-8896-1153 Molecular and Clinical Sciences Research Institute, St. George's, University of London, UK Search for more papers by this author Daniel PS Osborn Ji-Young Lee Masatake Araki Institute Resource Development Analysis, Kumamoto University, Kumamoto, Japan Kimi Timothy Mohun Francis Crick...
Abstract Alterations of Ca 2+ homeostasis have been implicated in a wide range neurodegenerative diseases. efflux from the endoplasmic reticulum into cytoplasm is controlled by binding inositol 1,4,5-trisphosphate to its receptor. Activated receptors are then rapidly degraded reticulum-associated degradation pathway. Mutations genes encoding neuronal isoform receptor ( ITPR1 ) and involved ERLIN1, ERLIN2 known cause hereditary spastic paraplegia (HSP) cerebellar ataxia. We provide evidence...
Abstract Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disorder, yet genetic cause of up to 50% cases remains unknown. Here, we show that mutations in KLHL24 HCM humans. Using genome-wide linkage analysis and exome sequencing, identified homozygous two consanguineous families with HCM. Of 11 young affected adults identified, 3 died suddenly 1 had a cardiac transplant due heart failure. member Kelch-like protein family, which acts as substrate-specific adaptors...
Congenital myopathies are typically characterised by early onset hypotonia, weakness and hallmark features on biopsy. Despite the rapid pace of gene discovery, ∼50% patients with a congenital myopathy remain without genetic diagnosis following screening known disease genes. We performed exome sequencing two consanguineous probands diagnosed muscle biopsy showing selective atrophy/hypotrophy or absence type II myofibres. identified variants in (MYL1) encoding skeletal fast-twitch specific...
Variants in genes encoding sarcomeric proteins are the most common cause of inherited cardiomyopathies. However, underlying genetic remains unknown many cases. We used exome sequencing to reveal etiology patients with recessive familial cardiomyopathy.Exome was carried out three consanguineous families. Functional assessment variants performed.Affected individuals presented hypertrophic or dilated cardiomyopathy variable severity from infantile- early adulthood-onset and sudden cardiac...
CCDC28B encodes a coiled coil domain-containing protein involved in ciliogenesis that was originally identified as second site modifier of the ciliopathy Bardet–Biedl syndrome. We have previously shown depletion leads to shortened cilia; however, mechanism underlying how this controls ciliary length is unknown. Here, we show interacts with SIN1, component mTOR complex 2 (mTORC2), and interaction important both context signaling hitherto unknown, mTORC-independent role SIN1 cilia biology....
Common intronic variants in the Human fat mass and obesity-associated gene (FTO) are found to be associated with an increased risk of obesity. Overexpression FTO correlates food intake obesity, whilst loss-of-function results lethality severe developmental defects. Despite intense scientific discussions around role energy metabolism, function during development remains undefined. Here, we show that loss Fto leads defects such as growth retardation, craniofacial dysmorphism aberrant neural...
The zebrafish embryo offers a tractable model to study organogenesis and human genetic disease. Despite its relative simplicity, the kidney develops functions in almost same way as humans. A major difference construction of is presence millions nephrons compared that has only two. However, simplifying such complex system into basic functional units aided our understanding how operates. In zebrafish, midline located glomerulus responsible for initial blood filtration two pronephric tubules...
Primary cilia are involved in important developmental and disease pathways, such as the regulation of neurogenesis tumorigenesis. They function sensory antennae essential key extracellular signalling systems. We have investigated effects cell stress on primary cilia. Exposure mammalian cells vitro, zebrafish vivo, to elevated temperature resulted rapid loss by resorption. In correlated with a reduction hedgehog signalling. Heat-shock-dependent was decreased where histone deacetylases (HDACs)...
Elevations of intracellular free Ca2+ concentration ([Ca2+]i) are a potent trigger for Weibel-Palade body (WPB) exocytosis and secretion von Willebrand factor (VWF) from endothelial cells; however, the identity WPB-associated Ca2+-sensors involved in transducing acute increases [Ca2+]i into granule remains unknown. Here, we show that synaptotagmin 5 (SYT5) is expressed human umbilical vein cells (HUVECs) recruited to WPBs regulate Ca2+-driven WPB exocytosis. Western blot analysis HUVECs...
Skeletal muscle derives from dorsal mesoderm formed during vertebrate gastrulation. Fibroblast growth factor (Fgf) signalling cooperates with Tbx transcription factors to promote formation, but their role in myogenesis has been unclear. Using zebrafish, we show that dorsally derived Fgf signals act through Tbx16 and Tbxta induce slow fast trunk precursors at distinct dorsoventral positions. binds directly activates the myf5 myod genes, which are required for commitment myogenesis. activity...