A5068869985- Zebrafish Biomedical Research Applications
- Epigenetics and DNA Methylation
- Congenital heart defects research
- Analog and Mixed-Signal Circuit Design
- Hematopoietic Stem Cell Transplantation
- Immune Cell Function and Interaction
- Developmental Biology and Gene Regulation
- TGF-β signaling in diseases
- Acute Myeloid Leukemia Research
- Angiogenesis and VEGF in Cancer
- Single-cell and spatial transcriptomics
- Renal and related cancers
- Pluripotent Stem Cells Research
- Low-power high-performance VLSI design
- CCD and CMOS Imaging Sensors
- Silicon Carbide Semiconductor Technologies
- Mesenchymal stem cell research
- Molecular Biology Techniques and Applications
- MicroRNA in disease regulation
- Advancements in Semiconductor Devices and Circuit Design
- Genomic variations and chromosomal abnormalities
- Nutrition, Genetics, and Disease
- Immune cells in cancer
- Electromagnetic Compatibility and Noise Suppression
- Aquaculture disease management and microbiota
University of Birmingham
2019-2024
Cancer Research UK Clinical Trials Unit
2021-2022
John Radcliffe Hospital
2011-2020
MRC Weatherall Institute of Molecular Medicine
2012-2020
University of Oxford
2010-2019
Hospital Geral de Bonsucesso
2019
Leiden University Medical Center
2015
British Heart Foundation
2013
Leiden University
2012
Madan Parque
2010
A number of human congenital disorders present with both heart and limb defects, consistent common genetic pathways. We have recently shown that the LIM homeodomain transcription factor islet 1 (Isl1) marks a subset cardiac progenitors. Here, we perform lineage studies an Isl1Cre mouse line to demonstrate Isl1 also In progenitors, expression is downregulated as progenitors migrate in form either or limb. To investigate heart-limb pathways Isl1-expressing ablated Type I Bmp receptor, Bmpr1a...
In the mammalian brain, neurogenesis continues only in few regions of forebrain. The molecular signals governing these unique neurogenic niches, however, are still ill defined. Here, we show that bone morphogenic protein (BMP)-mediated signaling is active adult neural stem cells and crucial to initiate lineage mouse subependymal zone. Conditional deletion Smad4 severely impairs neurogenesis, this phenocopied by infusion Noggin, an extracellular antagonist BMP. stem, but not progenitor cells,...
Deletion of various bone morphogenetic proteins (BMPs) and their downstream Smads in mice have clearly shown that BMP signaling is essential for the formation primordial germ cells (PGCs). However, molecular mechanism through which this takes place still unclear. Here, we demonstrate BMP4 produced extraembryonic ectoderm signals ALK2, a type I receptor, visceral endoderm (VE) to induce PGCs from epiblast. Firstly, embryonic day 5.5–6.0 (E5.5–E6.0) embryos cultured on fibronectin formed...
The mechanisms by which arterial fate is established and maintained are not clearly understood. Although a number of signaling pathways transcriptional regulators have been implicated in arterio-venous differentiation, none essential for formation, the manner widely expressed factors may achieve arterial-specific gene regulation unclear. Using both mouse zebrafish models, we demonstrate here that specification regulated combinatorially Notch SoxF transcription factors, via direct activation....
Hematopoietic stem cells (HSCs) are self-renewing multipotent that generate mature blood lineages throughout life. They, together with hematopoietic progenitor (collectively known as HSPCs), emerge from hemogenic endothelium in the floor of embryonic dorsal aorta by an endothelial-to-hematopoietic transition (EHT). Here we demonstrate transforming growth factor β (TGFβ) is required for HSPC specification and it regulates expression Notch ligand Jagged1a endothelial prior to EHT, a striking...
Abstract Adult haematopoiesis is the outcome of distinct haematopoietic stem cell (HSC) subtypes with self-renewable repopulating ability, but different lineage outputs. The molecular basis for this heterogeneity largely unknown. BMP signalling regulates HSCs as they are first generated in aorta-gonad-mesonephros region, at later developmental stages, its role controversial. Here we show that murine fetal liver and bone marrow two types can be prospectively isolated—BMP activated non-BMP...
Signaling by bone morphogenetic proteins is essential for a wide variety of developmental processes. Receptor-regulated Smad proteins, Smads 1 and 5, are intracellular mediators protein signaling. Together with Smad4, these translocate to the nucleus modulate transcription binding specific sequences on promoters target genes. We sought map transcriptional Smad1/5 activity in development generating embryonic stem cell lines carrying Smad1/5-specific response element derived from Id1 promoter...
SummaryVEGFA signaling is critical for endothelial and hematopoietic stem cell (HSC) specification. However, blood defects resulting from perturbation of the VEGFA pathway are always accompanied by impaired vascular/arterial development. Because HSCs derive arterial cells, it unclear whether directly contributes to HSC This an important question our understanding how formed developing their production in vitro. Through knockdown regulator ETO2 embryogenesis, we report a specific decrease...
Signaling by Bone Morphogenetic Proteins (BMP) has been implicated in early lung development, adult homeostasis and tissue-injury repair. However, the precise mechanism of action spatio-temporal pattern BMP-signaling during these processes remains inadequately described. To address this, we have utilized a transgenic line harboring BMP-responsive eGFP-reporter allele (BRE-eGFP) to construct first detailed spatiotemporal map canonical BMP-pathway activation adult-lung injury We demonstrate...
Abstract Haematopoietic stem cells are generated from the haemogenic endothelium (HE) located in floor of dorsal aorta (DA). Despite being integral to arteries, it is controversial whether HE and arterial share a common lineage. Here, we present transgenic zebrafish runx1 reporter line isolate aortic roof (ARE)s, excluding non-aortic endothelium. Transcriptomic analysis these populations identifies Runx1-regulated genes shows that initially expresses markers at similar levels ARE....
Abstract Bone morphogenetic protein (BMP) signaling is a key pathway in the patterning and development of organisms as diverse fruit fly humans. However, determination net BMP signaling, paramount to understanding organogenesis, limited analysis fixed material. We generated transgenic mouse that reports transcriptional response Smad activation by coupling well established element (BRE), isolated from Id1 promoter, green fluorescent ( BRE:gfp ). monitored activity fresh embryos. GFP...
In recent years, the perception of Z-disc function has changed from a passive anchor for myofilaments that allows transmission force, to dynamic multicomplex structure, capable sensing and transducing extracellular signals. Here, we describe new protein, which named CHAP (cytoskeletal heart-enriched actin-associated protein), expressed in differentiating heart skeletal muscle vitro vivo. Interestingly, addition its sarcomeric localization, was also able translocate nucleus. associated with...
Abstract Gata2 is a key transcription factor required to generate Haematopoietic Stem and Progenitor Cells (HSPCs) from haemogenic endothelium (HE); misexpression of leads haematopoietic disorders. Here we deleted conserved enhancer (i4 enhancer) driving pan-endothelial expression the zebrafish gata2a showed that Gata2a for HE programming by regulating runx1 second orthologue, gata2b . By 5 days, homozygous Δi4/Δi4 larvae normal numbers HSPCs, recovery mediated Notch signalling in HE....
The differentiation of hematopoietic stem cells (HSCs) is tightly controlled to ensure a proper balance between myeloid and lymphoid cell output. GATA2 pivotal transcription factor required for generation maintenance HSCs. expressed throughout development, but because early embryonic lethality in mice, its role during adult hematopoiesis incompletely understood. Zebrafish contains 2 orthologs GATA2: Gata2a Gata2b, which are different types. We show that the mammalian functions split these...
Operating power MOSFET devices at frequencies over 1 MHz will pose significant challenges to established electronic packages such as the D2-Pak and wirebonded SO-8 devices. In this paper high frequency parasitic impedances of a range are presented. Results show that source mounted package technology based upon copper clip type assembly has considerably lower impedance compared conventional packaging in 500 kHz MHz. The resistance recorded increases significantly approaches 1MHz. This is...
Abstract Deficiency of adenosine deaminase 2 (DADA2) is an inborn error immunity caused by loss-of-function mutations in the ( ADA2 ) gene. Clinical manifestations DADA2 include vasculopathy and immuno-hematological abnormalities, culminating bone marrow failure. A major gap exists our knowledge regulatory functions during inflammation hematopoiesis, mainly due to absence orthologue rodents. Exploring these mechanisms essential for understanding disease pathology developing new treatments....
Introduction: Burns cause serious damage and are a public health problem, with high mortality complications. Patients major burns face malnutrition infections, requiring specialized nutritional monitoring due to hypermetabolism. This study analyzed the post-discharge care network for these patients, evaluating support in recovery prevention of Methodology: The research is quantitative, descriptive, cross-sectional retrospective. 49 burn patients admitted Burn Unit Hospital Regional da Asa...
Introduction: Burns cause serious damage and are a public health problem, with high mortality complications. Patients major burns face malnutrition infections, requiring specialized nutritional monitoring due to hypermetabolism. This study analyzed the post-discharge care network for these patients, evaluating support in recovery prevention of Methodology: The research is quantitative, descriptive, cross-sectional retrospective. 49 burn patients admitted Burn Unit Hospital Regional da Asa...