A5035883533- Adipose Tissue and Metabolism
- Zebrafish Biomedical Research Applications
- Adipokines, Inflammation, and Metabolic Diseases
- Developmental Biology and Gene Regulation
- Congenital heart defects research
- Cardiovascular Disease and Adiposity
- Regulation of Appetite and Obesity
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Hippo pathway signaling and YAP/TAZ
- Connective tissue disorders research
- Cancer Cells and Metastasis
- Complement system in diseases
- Data Analysis with R
- Fish Ecology and Management Studies
- Genetics, Aging, and Longevity in Model Organisms
- Hedgehog Signaling Pathway Studies
- Cancer Genomics and Diagnostics
- Lipid metabolism and biosynthesis
- Trypanosoma species research and implications
- Biochemical Analysis and Sensing Techniques
- Cancer, Lipids, and Metabolism
- Subterranean biodiversity and taxonomy
- Cancer-related gene regulation
- Research on Leishmaniasis Studies
- Parasite Biology and Host Interactions
University of Edinburgh
2016-2024
Duke University
2015-2020
Edinburgh College
2019
British Heart Foundation
2017-2018
University of North Carolina at Chapel Hill
2011-2017
The Queen's Medical Research Institute
2017
King's College London
2006-2013
Medawar Building for Pathogen Research
2005
University of Oxford
2005
The Pax3/7 gene family has a fundamental and conserved role during neural crest formation. In people, PAX3 mutation causes Waardenburg syndrome, murine Pax3 is essential for pigment However, it unclear exactly how functions within the crest. Here we show that pax3 expressed before other pax3/7 members, including duplicated pax3b, pax7 pax7b genes, early in zebrafish development. Knockdown of protein by antisense morpholino oligonucleotides results defective fate specification xanthophores,...
Hypothalamic melanocortin neurons play a pivotal role in weight regulation. Here, we examined the contribution of Semaphorin 3 (SEMA3) signaling to development these circuits. In genetic studies, found 40 rare variants SEMA3A-G and their receptors (PLXNA1-4; NRP1-2) 573 severely obese individuals; disrupted secretion and/or through multiple molecular mechanisms. Rare this set genes were significantly enriched 982 cases compared 4,449 controls. zebrafish mutagenesis screen, deletion 7 pathway...
Trypanosoma brucei is a protozoan parasite that causes African sleeping sickness. T. multiplies extracellularly in the bloodstream, relying on antigenic variation of dense variant surface glycoprotein (VSG) coat to escape antibody-mediated lysis. We investigated role VSG proliferation and pathogenicity by using inducible RNA interference ablate transcript down 1-2% normal levels. Inhibiting synthesis vitro triggers rapid specific cell cycle checkpoint blocking division. Parasites arrest at...
Somatic growth and adipogenesis are closely associated with the development of obesity in humans. In this study, we identify a zebrafish mutant, vizzini, that exhibits both severe defect somatic increased accumulation adipose tissue. Positional cloning vizzini revealed premature stop codon gh1. Although effects GH largely through igfs mammals, found no decrease expression igf transcripts gh1 mutants during larval development. As progressed, however, overall to be progressively retarded...
The zebrafish model system offers significant utility for in vivo imaging of adipose tissue (AT) dynamics, and screening to identify chemical genetic modifiers adiposity. In particular, AT can be accurately quantified live using fluorescent lipophilic dyes (FLDs). Although, this methodology considerable promise, the comprehensive identification classification ATs has not been performed. Here we utilize FLDs systematically identify, classify quantify pool. We 34 regionally distinct ATs,...
Significance PLEXIN D1 ( PLXND1 ) has been implicated in body fat distribution and type 2 diabetes by genome-wide association studies, but the mechanism is unknown. We show here that Plxnd1 regulates zebrafish controlling visceral adipose tissue (VAT) growth mechanism. deficiency resulted induction of a hyperplastic state reduced lipid deposition VAT. Regulation VAT was dependent on V collagen, col5a1 , suggesting controls determining status extracellular matrix. Plxnd1-deficient were...
Abstract Fat distribution is an independent cardiometabolic risk factor. However, its molecular and cellular underpinnings remain obscure. Here we demonstrate that two GWAS signals at RSPO3 , which are associated with increased body mass index-adjusted waist-to-hip ratio, act to specifically increase expression in subcutaneous adipocytes. These variants also reduced lower-body fat, enlarged gluteal adipocytes insulin resistance. Based on human studies may limit gluteofemoral adipose tissue...
Obesity is a major public health crisis, affecting billions worldwide and increasing the risk of metabolic cardiovascular diseases. While lifestyle factors play role, genetic variation key determinant both obesity susceptibility efficacy treatment strategies. Recent studies have implicated Semaphorin 3 signalling pathway in obesity; however, specific roles for components remain largely unexplored. Here, we focus on Class A Plexins their potential contributions to body weight regulation....
Adipose tissues exhibit a remarkable capacity to expand, regress, and remodel in response energy status. The cellular mechanisms underlying adipose remodelling are central metabolic health. Hypertrophic remodelling, characterised by the enlargement of existing adipocytes, is associated with insulin resistance, type 2 diabetes, cardiovascular disease. In contrast, hyperplastic which new adipocytes generated, linked improved outcomes. Despite its clinical importance, regulation hypertrophic...
Striated muscles that enable mouth opening and swallowing during feeding are essential for efficient energy acquisition, likely to have played a fundamental role in the success of early jawed vertebrates. The developmental origins genetic requirements these uncertain. Here, we determine by indelible lineage tracing mouse fibres sternohyoid muscle (SHM), which is feeding, oesophageal striated (OSM), crucial voluntary swallowing, arise from Pax3-expressing somite cells. In vivo Kaede zebrafish...
Adipose tissues often exhibit subtle, quantitative differences between individuals, leading to a graded series of adiposity phenotypes at the population level. Robust, analyses are vital for studying these differences. In this Commentary we highlight two articles from our lab that employ sensitive new methods in zebrafish capable delineating complex and phenotypes. first article, utilized vivo imaging systematically quantify adipose tissues. We identified 34 regionally distinct developed...
Non-communicable diseases (NCDs) such as cardiovascular disease, diabetes and cancer were responsible for 68% of all deaths worldwide in 2012. The regional distribution lipid deposited within adipose tissue (AT) - so called body fat (BFD) is a strong risk factor NCDs. BFD highly heritable; however, the genetic basis almost entirely unknown. Genome-wide association studies have identified several loci associated with BFD, including at Plexin D1 (PLXND1) gene known to modulate angiogenesis. We...
There was an error published in Development140, 2972-2984.On p. 2973, Tg(mylz2:egfp) incorrectly attributed (Ju et al., 2003). This transgenic fish line made using the same DNA construct but Ingham laboratory (von Hofsten 2008) and has full name Tg(-2.2mylz2:GFP)i135 (see http://zfin.org/action/fish/fish-detail/ZDB-GENO-081119-5,ZDB-GENOX-081230-24).von Hofsten, J., Elworthy, S., Gilchrist, M. Smith, J. C., Wardle, F. C. Ingham, P. W. (2008). Prdm1- Sox6-mediated transcriptional repression...
A biallelic missense mutation in mitofusin 2 (MFN2) causes multiple symmetric lipomatosis and partial lipodystrophy, implicating disruption of mitochondrial fusion or interaction with other organelles adipocyte differentiation, growth and/or survival. In this study, we aimed to document the impact loss 1 (Mfn1) (Mfn2) on adipogenesis cultured cells.