A5083637069- Angiogenesis and VEGF in Cancer
- Mesenchymal stem cell research
- Adipose Tissue and Metabolism
- Coronary Interventions and Diagnostics
- MicroRNA in disease regulation
- Hematopoietic Stem Cell Transplantation
- Protein Kinase Regulation and GTPase Signaling
- Birth, Development, and Health
- Cancer-related molecular mechanisms research
- Peripheral Artery Disease Management
- Kruppel-like factors research
- Growth Hormone and Insulin-like Growth Factors
- Adipokines, Inflammation, and Metabolic Diseases
- Diabetic Foot Ulcer Assessment and Management
- Nuclear Receptors and Signaling
- Lipid metabolism and disorders
- Barrier Structure and Function Studies
- Estrogen and related hormone effects
- Hippo pathway signaling and YAP/TAZ
- Protein Tyrosine Phosphatases
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Amino Acid Enzymes and Metabolism
- Pancreatic function and diabetes
- Chemokine receptors and signaling
- Hematological disorders and diagnostics
University of Leicester
2010-2024
Medical Research Council
2010-2022
Montreal Clinical Research Institute
2002-2022
University of Bristol
2016-2021
Bristol Royal Infirmary
2019
NIHR Bristol Cardiovascular Biomedical Research Unit
2016-2019
MRC Toxicology Unit
2014
Inserm
2009-2012
Nantes Université
2009-2012
Institut du Thorax
2009-2012
Mechanisms that regulate signal propagation through the ERK/MAPK pathway are still poorly understood. Several proteins suspected to play critical roles in this process. One of these is Kinase Suppressor Ras (KSR), a component previously identified RAS-dependent genetic screens Drosophila and Caenorhabditis elegans . Here, we show KSR functions upstream MEK within module. In agreement with this, found facilitates phosphorylation by RAF. We further associates independently RAF MEK,...
We determined the effects of maternal diet-induced obesity on offspring adipose tissue insulin signalling and miRNA expression in aetiology resistance later life. Although body composition glucose tolerance 8-week-old male obese dams were not dysregulated, serum was significantly (p<0.05) elevated. Key proteins down-regulated, including receptor, catalytic (p110β) regulatory (p85α) subunits PI3K as well AKT1 2 (all p<0.05). The largest reduction observed IRS-1 protein (p<0.001), which...
Obesity during pregnancy has a long-term effect on the health of offspring including risk developing metabolic syndrome. Using mouse model maternal diet-induced obesity, we employed genome-wide approach to investigate microRNA (miRNA) and miRNA transcription profile in adipose tissue understand mechanisms through which this occurs. Male obese mothers, fed control diet from weaning, showed no differences body weight or adiposity at 8 weeks age. However, dams had up-regulated cytokine (Tnfα; P...
Fat accumulates in bone marrow (BM) of patients with diabetes. In this study, we investigated the mechanisms and consequences phenomenon. BM mesenchymal stromal cells (BM-MSCs) from type 2 diabetes (T2D) constitutively express adipogenic markers robustly differentiate into adipocytes (ADs) upon vitro induction as compared BM-MSCs subjects without Moreover, BM-ADs T2D (T2D BM-ADs) paracrinally stimulate a transcriptional program BM-MSCs. Antagonism MCP-1, chemokine pivotally expressed BM-ADs,...
Previous studies have shown that diabetes mellitus destabilises the integrity of microvasculature in different organs by damaging interaction between pericytes and endothelial cells. In bone marrow, exert trophic functions on cells haematopoietic through paracrine mechanisms. However, whether marrow are a target diabetes-induced damage remains unknown. Here, we investigated type 2 can affect abundance function pericytes. We conducted an observational clinical study comparing...
Rho guanine nucleotide exchange factors (Rho GEFs) are responsible for protein activation by catalyzing the of GDP GTP. Although overactivation proteins is a common component pathogenesis vascular disorders, molecular mechanisms and GEFs regulating activity Rho-dependent functions in smooth muscle cells (VSMC) still unknown. The aim this study was thus to identify involved regulation VSMC functions. By functional screening based on small interfering RNA (siRNA)-mediated silencing 27 GEFs, we...
Sustained overactivation of RhoA is a common component for the pathogenesis several cardiovascular disorders, including hypertension. Although activity Rho proteins depends on exchange factors (Rho-GEFs), identity Rho-GEFs expressed in vascular smooth muscle cells (VSMC) and participating control protein Rho-dependent functions remains unknown. To address this question, we analyzed by quantitative RT-PCR expression profile 28 RhoA-GEFs arteries normotensive (saline-treated) hypertensive (ANG...
OBJECTIVE In patients with type 2 diabetes (T2D) and critical limb ischemia (CLI), migration of circulating CD34+ cells predicted cardiovascular mortality at 18 months after revascularization. This study aimed to provide long-term validation mechanistic understanding the biomarker. RESEARCH DESIGN AND METHODS The association between cell was reassessed 6 years a new series T2D-CLI control subjects, immuno-sorted bone marrow were profiled for miRNA expression assessed apoptosis angiogenesis...
<b>Objective</b>. In patients with type 2 diabetes (T2D) and critical limb ischemia (CLI), migration of circulating CD34<sup>+</sup> cells predicted cardiovascular mortality at 18 months post-revascularization. This study aimed to provide long-term validation mechanistic understanding the biomarker. <p><b>Research Design Methods</b>. The association between cell was reassessed 6 years a new series T2D-CLI control subjects, immuno-sorted bone marrow...
<b>Objective</b>. In patients with type 2 diabetes (T2D) and critical limb ischemia (CLI), migration of circulating CD34<sup>+</sup> cells predicted cardiovascular mortality at 18 months post-revascularization. This study aimed to provide long-term validation mechanistic understanding the biomarker. <p><b>Research Design Methods</b>. The association between cell was reassessed 6 years a new series T2D-CLI control subjects, immuno-sorted bone marrow...
Abstract Background/Introduction The annual rate of restenosis, amputation, and death subjects with type 2 diabetes (T2DM) critical limb ischemia (CLI) is very high even after successful revascularization. We have recently demonstrated that the in-vitro migratory ability proangiogenic bone marrow (BM)-derived CD45dimKDR+CXCR4+ CD34+ cells predicts cardiovascular mortality at 18 months percutaneous angioplasty (PTA) in people T2DM CLI. Purpose To verify predictor a longer follow-up time to...
Abstract Mir483 is a conserved and highly expressed microRNA in placental mammals, embedded within the Igf2 gene. Here, we uncover control mechanisms physiological functions of vivo , by generating constitutive loss-of-function over-expressing mice. expression imprinted dependent on promoters Igf2/H19 imprinting region. Over-expression causes severe mid-gestation fetal, but not placental, growth restriction, late lethality. Fetal death prevented restoring to endogenous levels using an...