
Erwin PauwsUniversity College London | UCL · Great Ormond Street Institute of Child Health
Erwin Pauws
BSc PhD SFHEA
About
74
Publications
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Introduction
The research in my lab aims to identify the underlying, causative molecular and cellular mechanisms of common craniofacial birth defects, with a particular interest in cleft palate and craniosynostosis.
Ultimately the hope is that a better understanding of the pathogenesis of these congenital anomalies will translate to improved diagnosis, prognosis and treatment.
Additional affiliations
December 2015 - June 2023
May 2009 - December 2015
Position
- Research Associate
Education
August 1998 - May 2003
August 1989 - May 1994
Publications
Publications (74)
Craniofacial defects involving the lip and/or palate are among the most common human birth defects. X-linked cleft palate and ankyloglossia results from loss-of-function mutations in the gene encoding the T-box transcription factor TBX22. Further studies show that TBX22 mutations are also found in around 5% of non-syndromic cleft palate patients. A...
Syndromic craniosynostosis caused by mutations in FGFR2 is characterised by developmental pathology in both endochondral and membranous skeletogenesis. Detailed phenotypic characterisation of features in the membranous calvarium, the endochondral cranial base and other structures in the axial and appendicular skeleton has not been performed at embr...
Craniosynostosis is a common craniofacial birth defect. This review focusses on the advances that have been achieved through studying the pathogenesis of craniosynostosis using mouse models. Classic methods of gene targeting which generate individual gene knockout models have successfully identified numerous genes required for normal development of...
FGFR2c regulates many aspects of craniofacial and skeletal development. Mutations in the FGFR2 gene are causative for multiple forms of syndromic craniosynostosis, including Crouzon syndrome. Paradoxically, mouse studies have shown that both the activation (Fgfr2cC342Y; a mouse model for human Crouzon syndrome), as well as the removal (Fgfr2cnull)...
Children with syndromic forms of craniosynostosis undergo a plethora of surgical interventions to resolve the clinical features caused by the premature fusion of cranial sutures. While surgical correction is reliable, the need for repeated rounds of invasive treatment puts a heavy burden on the child and their family. This study explores a non-surg...
The Chiari II brain malformation affects 90% of children with open spina bifida. The hindbrain herniates through the foramen magnum into the vertebral canal leading to frequent hydrocephalus and occasional respiratory emergency. Chiari II is not confined to the back of the brain, but is a global brain syndrome, with supratentorial defects that are...
Crouzon syndrome is a congenital craniofacial disorder caused by mutations in the Fibroblast Growth Factor Receptor 2 (FGFR2). It is characterized by the premature fusion of cranial sutures, leading to a brachycephalic head shape, and midfacial hypoplasia. The aim of this study was to investigate the effect of the FGFR2 mutation on the microarchite...
X-ray Computed Tomography (CT) images are widely used in various fields of natural, physical, and biological sciences. 3D reconstruction of the images involves segmenta-tion of the structures of interest. Manual segmentation has been widely used in the field of biological sciences for complex structures composed of several sub-parts and can be a ti...
Premature fusion of craniofacial joints, i.e. sutures, is a major clinical condition. This condition affects children and often requires numerous invasive surgeries to correct. Minimally invasive external loading of the skull has shown some success in achieving therapeutic effects in a mouse model of this condition, promising a new non-invasive tre...
Syndromic craniosynostosis (CS) patients exhibit early, bony fusion of calvarial sutures and cranial synchondroses, resulting in craniofacial dysmorphology. In this study, we chronologically evaluated skull morphology change after abnormal fusion of the sutures and synchondroses in mouse models of syndromic CS for further understanding of the disea...
Children with syndromic forms of craniosynostosis undergo a plethora of surgical interventions to resolve the clinical features caused by the premature fusion of cranial sutures. While surgical correction is reliable, the need for repeated rounds of invasive treatment puts a heavy burden on the child and their family. This study explores a non-surg...
We present a family with a previously undescribed abnormality of the palate and oropharynx which involved the absence of the uvula and the anterior pillar of the fauces, rudimentary posterior pillar of the fauces, and hypernasality. Eight family members over 4 generations are affected in a pattern consistent with autosomal dominant inheritance. A c...
Introduction
Our understanding of the biomechanical changes that occur during normal mouse skull growth is still limited. The aim of this study was a comprehensive characterization of normal mouse skull growth in terms of its morphology, intracranial pressure, bone and cranial joint (suture) mechanical properties, and the biomechanical strain exper...
This study investigated the genetic basis of an unusual autosomal dominant phenotype characterized by familial absent uvula, with a short posterior border of the soft palate, abnormal tonsillar pillars, and velopharyngeal insufficiency. Cytogenetic analysis and single-nucleotide polymorphism–based linkage analysis were investigated in a 4-generatio...
Craniofacial microsomia (CFM) is characterized by unilateral or bilateral underdevelopment of the facial structures arising from the first and second pharyngeal arches, but extracraniofacial anomalies may also be present. This retrospective study provides an overview of the prevalence, types, and characteristics of extracraniofacial anomalies in pa...
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TDP-43 (encoded by the gene TARDBP) is an RNA binding protein central to the pathogenesis of amyotrophic lateral sclerosis (ALS). However, how TARDBP mutations trigger pathogenesis remains unknown. Here, we use novel mouse mutants carrying point mutations in endogenous Tardbp to dissect TDP-43 function at physiological levels both in vitro and in v...
During postnatal calvarial growth the brain grows gradually and the overlying bones and sutures accommodate that growth until the later juvenile stages. The whole process is coordinated through a complex series of biological, chemical and perhaps mechanical signals between various elements of the craniofacial system. The aim of this study was to in...
The aim of this study was to compare the anatomical differences in the skull base between the affected and non-affected side in patients with craniofacial microsomia (CFM), and to compare the affected and non-affected sides with measurements from a normal population. Three-dimensional computed tomography scans of 13 patients with unilateral CFM and...
Craniofacial development requires a complex series of coordinated and finely tuned events to take place, during a relatively short time frame. These events are set in motion by switching on and off transcriptional cascades that involve the use of numerous signalling pathways and a multitude of factors that act at the site of gene transcription. It...
Orofacial clefts affecting the lip and/or palate are among the most common birth defects worldwide (1/700 live births) and are understood to result from a wide variety of genetic and environmental causes. There are several commonly applied distinctions that classify orofacial clefts, namely cleft lip with or without cleft palate (CL/P) and cleft pa...
Human ZIC1 (zinc finger protein of cerebellum 1), one of five homologs of the Drosophila pair-rule gene odd-paired, encodes a transcription factor previously implicated in vertebrate brain development. Heterozygous deletions of ZIC1 and its nearby paralog ZIC4 on chromosome 3q25.1 are associated with Dandy-Walker malformation of the cerebellum, and...
The mammalian cranial vault largely consists of five flat bones that are joined together along their edges by soft fibrous tissues called sutures. Premature closure of the cranial su-tures, craniosynostosis, can lead to serious clinical pathology unless there is surgical intervention. Research into the genetic basis of the disease has led to the de...
Identifying genes that are important for embryo development is a crucial first step towards understanding their many functions in driving the ordered growth, differentiation and organogenesis of embryos. It can also shed light on the origins of developmental disease and congenital abnormalities. Current international efforts to examine gene functio...
X-linked cleft palate (CPX) is caused by mutations in the gene encoding the TBX22 transcription factor and is known to exhibit phenotypic variability, usually involving either a complete, partial or submucous cleft palate, with or without ankyloglossia. This study hypothesized a possible involvement of TBX22 in a family with X-linked, CHARGE-like A...
SUMO1 has been implicated as having a role in the causation of cleft lip with or without cleft palate (CLP), both directly and through association studies in humans and, perhaps more controversially, in transgenic mouse studies.
To screen for sequence variants that might be responsible for human CLP, we performed direct DNA sequence analysis in a w...
The fibroblast growth factor (FGF) signalling pathway is critically involved in several aspects of craniofacial development, including formation of the lip and the palate. FGF receptors are activated by extracellular FGF ligands in order to regulate cellular processes such as migration and morphogenesis through instruction of specific target gene e...
X-linked cleft palate and ankyloglossia (CPX) are caused by mutations in the TBX22 transcription factor. To investigate whether patients with ankyloglossia alone or in the presence of other craniofacial features including hypodontia or CLP might be caused by TBX22 mutations, we analyzed 45 Thai patients with isolated ankyloglossia, 2 unusual CPA fa...
Mutations in the T-box transcription factor gene TBX22 are found in patients with X-linked cleft palate and ankyloglossia (CPX), and are reported in approximately 5% of all non-syndromic cleft palate patients. Clinical variability in CPX ranges from a mild or occult submucous cleft palate to a severe, complete cleft of the secondary palate.
To expl...
Craniofacial development requires a complex series of coordinated and finely tuned events to take place, during a relatively
short time frame. These events are set in motion by switching on and off transcriptional cascades that involve the use of
numerous signalling pathways and a multitude of factors that act at the site of gene transcription. It...
The mammalian secondary palate exhibits morphological, pathological and molecular heterogeneity along the anteroposterior axis. Although the cell proliferation rates are similar in the anterior and posterior regions during palatal outgrowth, previous studies have identified several signaling pathways and transcription factors that specifically regu...
Inborn Errors of Development is the definitive work on genetically caused abnormalities of human development. Despite the explosion in genetic advances, the causes of two-thirds of all birth defects remain unknown. However, we are on the brink of a revolution in this area, and this book is at the forefront. It is the first book to connect the disea...
Owing to the complex aetiology and the variable penetrance of cleft lip and/or palate (CL/P), understanding the molecular basis has been challenging. Recent reports have identified two independent biochemical pathways that will help to elucidate the underlying pathology. Fibroblast growth factor signalling, previously known for its involvement in c...
Neural tube defects (NTDs), such as spina bifida, are common and severe birth defects in humans but the underlying causes
are poorly understood. The pathogenesis and etiology of spina bifida in the curly tail mouse closely resemble defects in humans, providing a well-characterized model of NTDs. Grainyhead-like-3 (Grhl3), which encodes a transcript...
The T-box transcription factor TBX22 is essential for normal craniofacial development, as demonstrated by the finding of nonsense, frameshift, splice-site, or missense mutations in patients with X-linked cleft palate (CPX) and ankyloglossia. To better understand the function of TBX22, we studied 10 different naturally occurring missense mutations t...
Serial analysis of gene expression (SAGE) was applied to compare expression profiles of normal thyroid tissue and papillary thyroid carcinoma (PTC). A SAGE tag corresponding to the partial cDNA for the small protein 31 (SMAP31) is upregulated approximately 13-fold in papillary thyroid cancer (PTC) and was selected for further research. BLAST-search...
To identify transcripts that distinguish malignant from benign thyroid disease serial analysis of gene expression (SAGE) profiles of papillary thyroid carcinoma and of normal thyroid are compared. Of the 21,000 tags analyzed, 204 tags are differentially expressed with statistical significance in the tumor. Thyroid tumor specificity of these transcr...
The coding region of the human thyroglobulin (TG) mRNA has been resequenced, and comparison with the TG sequence originally published in 1987 showed many variations. All of the variations were validated in 20--40 other alleles, and this resulted in the revision of 41 nucleotide positions. This review presents the revised wild-type human TG sequence...
A paradigm of molecular medicine is the identification of functionally specialized genes in the search of defects responsible for human disease. To identify novel genes relevant for thyroid physiology, we applied serial analysis of gene expression (SAGE) and identified 4260 tag sequences that did not match any known gene present in the GenBank data...
The coding region of the human thyrogloblulin (TG) mRNA has been resequenced, and comparison with the TG sequence originally published in 1987 showed many variations. All of the variations were validated in 20-40 other alleles. and this resulted in the revision of 41 nucleotide positions. This review presents the revised wild-type human TG sequence...
Characterization of the genetic background of pediatric thyroid carcinomas could aid in distinguishing between differently staged tumors with respect to treatment and prognosis. Two known genetic factors associated with thyroid carcinoma, the proto-oncogenes gsp and ras were investigated.
DNA was extracted from paraffin sections from both tumor and...
The analysis of a human thyroid serial analysis of gene expression (SAGE) library shows the presence of an abundant SAGE tag
corresponding to the mRNA of thyroglobulin (TG). Additional, less abundant tags are present that can not be linked to any
other known gene, but show considerable homology to the wild-type TG tag. To determine whether these ta...
SAGE enables the determination of genome-wide mRNA expression profiles. A comprehensive analysis of SAGE data requires software, which integrates (statistical) data analysis methods with a database system. Furthermore, to facilitate data sharing between users, the application should reside on a central server and be accessed via the internet. Since...
Motivation: SAGE enables the determination of genome-wide mRNA expression profiles. A comprehensive analysis of SAGE data requires software, which integrates (statistical) data analysis methods with a database system. Furthermore, to facilitate data sharing between users, the application should reside on a central server and be accessed via the int...
The assessment of the expression profile of normal human thyroid tissue using serial analysis of gene expression (SAGE) generated a collection of 10,994 sequence transcripts (tags). Each tag represented a messenger RNA transcript, and, in total, 6099 different tags could be distinguished. The presence and abundance of thyroid-specific transcripts s...
Serial analysis of gene expression (SAGE) was used to identify genes that might be involved in the development or growth of medulloblastoma, a childhood brain tumor. Sequence tags from medulloblastoma (10229) and fetal brain (10692) were determined. The distributions of sequence tags in each population were compared, and for each sequence tag, pair...
We developed a transient transfection system for human thyroglobulin (TG) cDNA in both human thyroid cells and in COS-1 cells.
Four overlapping TG cDNA fragments were amplified by reverse transcription-PCR from RNA of normal thyroid tissue. The most 5′ fragment includes the natural translation initiation site and the sequence encoding the signal pe...
On Dec 16, 1999 this sequence version replaced gi:2707180.
Questions
Question (1)
Standard proteinase K lysis of fecal pellets does not seem to work.
The main problem seems to be how to get rid of excess (fecal) material.
Any suggestions will be very welcome.
Thanks.