A5086004305- Hippo pathway signaling and YAP/TAZ
- Congenital heart defects research
- Pluripotent Stem Cells Research
- Axon Guidance and Neuronal Signaling
- Fibroblast Growth Factor Research
- Growth Hormone and Insulin-like Growth Factors
- Cancer, Hypoxia, and Metabolism
- Kruppel-like factors research
- Neuroblastoma Research and Treatments
- Genetic Syndromes and Imprinting
- Primate Behavior and Ecology
- Pancreatic function and diabetes
- Pituitary Gland Disorders and Treatments
- Hormonal Regulation and Hypertension
- Botany and Plant Ecology Studies
- Hedgehog Signaling Pathway Studies
- Renal and related cancers
- Epigenetics and DNA Methylation
- Animal Behavior and Welfare Studies
- Lichen and fungal ecology
- Adrenal and Paraganglionic Tumors
- Chromatin Remodeling and Cancer
- Ocular Disorders and Treatments
- Stress Responses and Cortisol
- TGF-β signaling in diseases
King's College London
2016-2025
STMicroelectronics (United Kingdom)
2021-2022
Australian Institute of Health and Welfare
2021
University of Edinburgh
2016
University of Roehampton
2013-2014
Royal Holloway University of London
1996
Sonic hedgehog (SHH) is an essential morphogenetic signal that dictates cell fate decisions in several developing organs mammals. In vitro data suggest SHH required to specify LHX3+/LHX4+ Rathke's pouch (RP) progenitor identity. However, vivo studies have failed reveal such a function, supporting instead crucial role for promoting proliferation of these RP progenitors and differentiation pituitary types. Here, we used genetic approach demonstrate activation the pathway necessary induce...
In response to physiological demand, the pituitary gland generates new hormone-secreting cells from committed progenitor throughout life. It remains unclear what extent stem (PSCs), which uniquely express SOX2, contribute growth and renewal. Moreover, neither signals that drive proliferation nor their sources have been elucidated. We used genetic approaches in mouse, showing WNT pathway is essential for of all lineages gland. reveal SOX2 + are a key source ligands. By blocking secretion WNTs...
Familial growth hormone deficiency provides an opportunity to identify new genetic causes of short stature. Here we combine linkage analysis with whole-genome resequencing in patients and maternally inherited gingival fibromatosis. We report that from three unrelated families harbor either two missense mutations, c.347G>T p.(Arg116Leu) or c.1106C>T p.(Pro369Leu), KCNQ1, a gene previously implicated the long QT interval syndrome. Kcnq1 is expressed hypothalamic GHRH neurons pituitary...
The pituitary gland is a primary endocrine organ that controls major physiological processes. Abnormal development or homeostatic disruptions can lead to human disorders such as hypopituitarism tumours. Multiple signalling pathways, including WNT, BMP, FGF and SHH regulate but the role of Hippo-YAP1/TAZ cascade currently unknown. In multiple tissues, Hippo kinase underlies neoplasias; it influences size through regulation proliferation apoptosis, has roles in determining stem cell potential....
SOX2 positive pituitary stem cells (PSCs) are specified embryonically and persist throughout life, giving rise to all endocrine lineages. We have previously shown the activation of STK/LATS/YAP/TAZ signalling cascade in developing postnatal mammalian pituitary. Here, we investigate function this pathway during development regulation cell compartment. Through loss- gain-of-function genetic approaches, reveal that restricting YAP/TAZ is essential for normal organ size specification from SOX2+...
Abstract Renewal of the catecholamine-secreting chromaffin cell population adrenal medulla is necessary for physiological homeostasis throughout life. Definitive evidence presence or absence an adrenomedullary stem has been enigmatic. In this work, we demonstrate that a subset sustentacular cells endowed with support role, are in fact cells. Through genetic tracing and comprehensive transcriptomic data mouse medulla, show expressing Sox2/ SOX2 specialise as unique postnatal from embryonic...
Abstract The primary cilium is an essential organelle that important for normal cell signalling during development and homeostasis but its role in pituitary has not been reported. facilitates signal transduction multiple pathways, the best‐characterised being SHH pathway, which known to be necessary correct gland development. FUZ a planar polarity (PCP) effector ciliogenesis, where cilia of Fuz −/− mutant s are shorter or non‐functional. part group proteins required recruiting retrograde...
Tumours of the anterior pituitary can manifest from all endocrine cell types but mechanisms for determining their specification are not known. The Hippo kinase cascade is a crucial signalling pathway regulating growth and fate in numerous organs. There mounting evidence implicating this tumour formation, where it emerging as an anti-cancer target. We previously demonstrated activity mouse nuclear association its effectors YAP/TAZ with SOX2-expressing stem cells. Here, we sought to...
Pituitary developmental defects lead to partial or complete hormone deficiency and significant health problems. The majority of cases are sporadic unknown cause. We screened 28 patients with pituitary stalk interruption syndrome (PSIS) for mutations in the FAT/DCHS family protocadherins that have high functional redundancy. identified seven variants, four which putatively damaging, FAT2 DCHS2 six recruited through a cohort mostly ectopic posterior gland and/or interruption. All had growth...
The Australian Institute of Health and Welfare (AIHW) has been providing support to the Government Department report on mental health-related data governments a frequent basis since April 2020 in form COVID-19 health services dashboards. These dashboards feature extensive use visualizations which illustrate change service over time as well comparisons with pre-pandemic levels use. Data are included from Medicare Benefits Schedule (MBS), Pharmaceutical Scheme (PBS/RPBS), Government-funded...
Abstract The distribution and succession of epiphytic other associated lichens on blackthorn (Prunus spinosa) growing the shingle at Dungeness is described. Some 33 species, which exhibited a range ecological strategies from pioneer to late colonizers, were recorded. Both rate change status (age) blackthorns progress lichen colonization seemed depend whether bushes directly or adjacent alluvial soil; both processes seeming be more rapid former substratum. Terricolous lichens, 18 recorded,...
Summary Renewal of the catecholamine-secreting chromaffin cell population adrenal medulla is necessary for physiological homeostasis throughout life. Definitive evidence presence or absence an adrenomedullary stem has been enigmatic. In this work, we demonstrate that a subset sustentacular cells endowed with support role, are in fact cells. Through genetic tracing and comprehensive transcriptomic data mouse medulla, show expressing Sox2/ SOX2 specialise as unique postnatal from embryonic...
The distribution and succession of epiphytic other associated lichens on blackthorn (Prunus spinosa) growing the shingle at Dungeness is described. Some 33 species, which exhibited a range ecological strategies from pioneer to late colonizers, were recorded. Both rate change status (age) blackthorns progress lichen colonization seemed depend whether bushes directly or adjacent alluvial soil; both processes seeming be more rapid former substratum. Terricolous lichens, 18 recorded, generally...
ABSTRACT In response to physiological demand, the pituitary gland generates new hormone-secreting cells from committed progenitor throughout life. It remains unclear what extent stem (PSCs), which uniquely express SOX2, contribute growth and renewal. Moreover, neither signals that drive proliferation nor their sources have been elucidated. We used genetic approaches in mouse, showing WNT pathway is essential for of all lineages gland. reveal SOX2 + are a key source ligands. By blocking...
We investigated the corneal morphology of adult Mp/+ mice, which are heterozygous for micropinna microphthalmia mutation, and identified several abnormalities, implied that epithelial maintenance was abnormal. The epithelium thin, loosely packed contained goblet cells in older mice. Evidence also suggested barrier function compromised. However, there no major effect on cell turnover mosaic patterns radial stripes indicated movement normal. Limbal blood vessels formed an abnormally wide...
SOX2+ pituitary stem cells (PSCs) are specified embryonically and persist throughout life, giving rise to all endocrine lineages. We have previously shown activation of the MST/LATS/YAP/TAZ signalling cascade in developing postnatal mammalian pituitary. Here, we investigate function this pathway during development regulation PSCs. Through loss- gain-of-function genetic approaches, reveal that restricting YAP/TAZ is essential for normal organ size specification from Postnatal deletion LATS...