A5056844359- Congenital heart defects research
- Epigenetics and DNA Methylation
- Renal and related cancers
- Genomics and Chromatin Dynamics
- Genomics and Rare Diseases
- Hemispheric Asymmetry in Neuroscience
- Genomic variations and chromosomal abnormalities
- RNA Research and Splicing
- Genetics and Neurodevelopmental Disorders
- Neonatal Respiratory Health Research
- Metabolism and Genetic Disorders
- Congenital Heart Disease Studies
- Muscle Physiology and Disorders
- Ubiquitin and proteasome pathways
- Wnt/β-catenin signaling in development and cancer
- Connective tissue disorders research
- Congenital Diaphragmatic Hernia Studies
- Genetic and Kidney Cyst Diseases
- Renal cell carcinoma treatment
- Hedgehog Signaling Pathway Studies
- Cerebrovascular and genetic disorders
- RNA and protein synthesis mechanisms
- Hippo pathway signaling and YAP/TAZ
- Kruppel-like factors research
- Autism Spectrum Disorder Research
King Abdullah University of Science and Technology
2024-2025
Genome Institute of Singapore
2021-2025
Agency for Science, Technology and Research
2017-2025
Institute of Medical Biology
2017-2021
A*STAR Graduate Academy
2017
Institut Curie
2011-2013
Centre National de la Recherche Scientifique
2012-2013
Dynamique du noyau
2012
Hôpital Necker-Enfants Malades
2009
Inserm
2009
Nuclear reprogramming is potentially important as a route to cell replacement and drug discovery, but little known about its mechanism. transfer eggs oocytes attempts identify the mechanism of this direct towards by natural components. Here we analyze how nuclei transplanted Xenopus exploits incorporation histone variant H3.3.After nuclear transplantation, oocyte-derived H3.3 not H3.2, deposited on several regions genome including rDNA, major satellite repeats, regulatory Oct4. This...
Discovering how histone variants that mark distinct chromatin regions affect a developmental program is major challenge in the epigenetics field. To assess importance of H3.3 variant and its dedicated chaperone HIRA, we used an established model, Xenopus laevis. After early rapid divisions exploiting large maternal pool both replicative H3.2 replacement H3.3, transcripts show peak expression at gastrulation. Depletion leads to gastrulation arrest. However, with only depletion, defects occur...
Meckel-Gruber syndrome (MKS) is a lethal fetal disorder characterized by diffuse renal cystic dysplasia, polydactyly, brain malformation that usually occipital encephalocele, and/or vermian agenesis, with intrahepatic biliary duct proliferation. Joubert (JBS) viable neurological characteristic "molar tooth sign" (MTS) on axial images reflecting cerebellar hypoplasia/dysplasia. Both conditions are classified as ciliopathies an autosomal recessive mode of inheritance. Allelism MKS and JBS has...
Abstract Developmental epileptic encephalopathies are devastating disorders characterized by intractable seizures and developmental delay. Here, we report an allelic series of germline recessive mutations in UGDH 36 cases from 25 families presenting with encephalopathy delay hypotonia. encodes oxidoreductase that converts UDP-glucose to UDP-glucuronic acid, a key component specific proteoglycans glycolipids. Consistent being loss-of-function alleles, show using patients’ primary fibroblasts...
The human respiratory epithelium is derived from a progenitor cell in the distal buds of developing lung. These "bud tip progenitors" are regulated by reciprocal signaling with surrounding mesenchyme; however, mesenchymal heterogeneity and function lung poorly understood. We interrogated single-cell RNA sequencing data multiple specimens identified population present during development that highly enriched for expression WNT agonist RSPO2, we found adjacent bud progenitors RSPO2 receptor...
Structural birth defects occur in approximately 3% of live births; most such lack defined genetic or environmental causes. Despite advances surgical approaches, pharmacologic prevention remains largely out reach.
Heterotaxy (HTX) is frequently caused by deleterious variants in the gene encoding Matrix metallopeptidase 21 (MMP21). However, underlying pathomechanism has not been ascertained. In this study, we report on a novel HTX-associated MMP21 knockout allele humans and investigate peptidase’s role during laterality development using Xenopus embryos as animal model. The targeted inactivation of mmp21 f0 mutant successfully phenocopied human HTX condition, yet cilia-driven leftward fluid flow, which...
Herein, we report the screening of a large panel genes in series 80 fetuses with congenital heart defects (CHDs) and/or heterotaxy and no cytogenetic anomalies. There were 49 males (61%/39%), family history 28 cases (35%) parental consanguinity 77 (96%). All had complex CHD except one who midline anomalies while 52 (65%) addition to CHD. Altogether, 29 (36%) extracardiac extra-heterotaxy A pathogenic variant was found 10/80 (12.5%) higher percentage group (8/52 cases, 15%) compared...
Heterotaxy (HTX) is frequently caused by deleterious variants in the gene encoding Matrix metallopeptidase 21 (MMP21). However, underlying pathomechanism has not been ascertained. In this study, we report on a novel HTX-associated MMP21 knockout allele humans and investigate peptidase’s role during laterality development using Xenopus embryos as animal model. The targeted inactivation of mmp21 f0 mutant successfully phenocopied human HTX condition, yet cilia-driven leftward fluid flow, which...
During kidney development, WNT/β-catenin signalling has to be tightly controlled ensure proliferation and differentiation of nephron progenitor cells. Here, we show in mice that the molecules RSPO1 RSPO3 act a functionally redundant manner permit their genetic deletion leads rapid decline progenitors. By contrast, tissue specific cap mesenchymal cells abolishes mesenchyme epithelial transition (MET) is linked loss Bmp7 expression, absence SMAD1/5 phosphorylation concomitant failure activate...
Abstract Developmental studies have shown that the evolutionarily conserved Wnt Planar Cell Polarity (PCP) pathway is essential for development of a diverse range tissues and organs including brain, spinal cord, heart sensory organs, as well establishment left-right body axis. Germline mutations in highly PCP gene VANGL2 humans only been associated with central nervous system malformations, functional testing to understand variant impact has not performed. Here we report three new families...
Article18 January 2023Open Access Source DataTransparent process A progeroid syndrome caused by a deep intronic variant in TAPT1 is revealed RNA/SI-NET sequencing Nasrinsadat Nabavizadeh orcid.org/0000-0002-1629-6956 Laboratory of Human Genetics & Therapeutics, Genome Institute Singapore, A*STAR, Singapore City, Division Genetics, Department Cell and Molecular Biology Microbiology, Faculty Biological Science Technology, University Isfahan, Iran Medical Department, Koç School Medicine,...
Abstract Variants in transcriptional activator Gli Kruppel Family Member 3 ( GLI3 ) have been reported to be associated with several phenotypes including Greig cephalopolysyndactyly syndrome (MIM #175700), Pallister‐Hall (PHS) #146510), postaxial polydactyly types A1 (PAPA1) and B (PAPB) #174200), preaxial type 4 #174700). All these disorders follow an autosomal dominant pattern of inheritance. Hypothalamic hamartomas 241800) is somatic variants . We report a related couple parents having...
SUMMARY Mammalian respiratory system development is regulated by complex reciprocal signaling events that take place between epithelial cells and the surrounding mesenchymal cells; however, heterogeneity function in developing human lung poorly understood. We interrogated single cell RNA sequencing data from multiple specimens identified a population present during highly enriched for expression of WNT agonist R-SPONDIN2 ( RSPO2 ), we found adjacent bud tip progenitors are receptor LGR5 . By...
Abstract Heterotaxy (HTX) is frequently caused by deleterious variants in the gene encoding Matrix metallopeptidase 21 (MMP21). However, underlying pathomechanism has not been ascertained. In this study, we report on a novel HTX-associated MMP21 knockout allele humans and investigate peptidase’s role during laterality development using Xenopus embryos as animal model. The targeted inactivation of mmp21 f0 mutant successfully phenocopied human HTX condition, yet cilia-driven leftward fluid...
Summary Impaired proteostasis can induce protein aggregation which is toxic to neuronal cells, contributing neurodegeneration and other signs of aging. In this study, we delineate an early-onset progressive neuropathy evoking Giant Axonal Neuropathy 1. The causative gene IVNS1ABP encodes a E3-ubiquitin ligase adaptor close gigaxonin paralogue. Patient-derived fibroblasts, iPSCs, neural progenitors exhibited hallmarks accumulation lysosomal dysfunction. Ubiquitome analysis revealed...