A5027660695- Protein Kinase Regulation and GTPase Signaling
- Metabolomics and Mass Spectrometry Studies
- Pancreatic function and diabetes
- Metabolism, Diabetes, and Cancer
- Lipid metabolism and biosynthesis
- Cellular transport and secretion
- Cancer, Lipids, and Metabolism
- Sphingolipid Metabolism and Signaling
- Cancer, Hypoxia, and Metabolism
- Adipose Tissue and Metabolism
- Advanced Proteomics Techniques and Applications
- Receptor Mechanisms and Signaling
- Dietary Effects on Health
- Genetics, Aging, and Longevity in Model Organisms
- Nitric Oxide and Endothelin Effects
- Cell Adhesion Molecules Research
- PI3K/AKT/mTOR signaling in cancer
- Lipid Membrane Structure and Behavior
- Mitochondrial Function and Pathology
- Ion channel regulation and function
- Peroxisome Proliferator-Activated Receptors
- ATP Synthase and ATPases Research
- Mass Spectrometry Techniques and Applications
- Endoplasmic Reticulum Stress and Disease
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Babraham Institute
2014-2023
Biotechnology and Biological Sciences Research Council
2022
University of London
2017-2018
University of Michigan
2015
University of Cambridge
2015
Birmingham Women's Hospital
2013
University Hospital Southampton NHS Foundation Trust
2013
Oxford Centre for Diabetes, Endocrinology and Metabolism
2013
Churchill Hospital
2013
University of Oxford
2013
There is a need for standardized, practical annotation structures of lipid species derived from mass spectrometric approaches; i.e., high-throughput data obtained instruments operating in either high- or low-resolution modes. This proposal based on common, officially accepted terms and builds upon the LIPID MAPS terminology. It aims to add defined levels information below nomenclature, as detailed chemical structures, including stereochemistry, are usually not automatically provided by...
Highlights•ACSS2 expression positively correlates with tumor stage and patient survival•Hypoxia low lipid availability synergistically stimulate ACSS2 expression•Acetate is a major source of carbon for synthesis during metabolic stress•ACSS2 required growth xenografts harboring copy-number gainsSummaryA functional genomics study revealed that the activity acetyl-CoA synthetase 2 (ACSS2) contributes to cancer cell under low-oxygen lipid-depleted conditions. Comparative metabolomics lipidomics...
A comprehensive and standardized system to report lipid structures analyzed by MS is essential for the communication storage of lipidomics data. Herein, an update on both LIPID MAPS classification shorthand notation presented categories Fatty Acyls (FA), Glycerolipids (GL), Glycerophospholipids (GP), Sphingolipids (SP), Sterols (ST). With its major changes, i.e., annotation ring double bond equivalents number oxygens, updated facilitates reporting newly delineated oxygenated species as well....
An in vivo model of antiangiogenic therapy allowed us to identify genes upregulated by bevacizumab treatment, including Fatty Acid Binding Protein 3 (FABP3) and FABP7, both which are involved fatty acid uptake. In vitro, were induced hypoxia a hypoxia-inducible factor-1α (HIF-1α)-dependent manner. There was significant lipid droplet (LD) accumulation that time O2 concentration dependent. Knockdown endogenous expression FABP3, or Adipophilin (an essential LD structural component)...
Autotaxin (ATX), or nucleotide pyrophosphatase-phosphodiesterase 2, is a secreted lysophospholipase D that promotes cell migration, metastasis, and angiogenesis. ATX generates lysophosphatidic acid (LPA), lipid mitogen motility factor acts on several G protein-coupled receptors. Here we report ATX-deficient mice die at embryonic day 9.5 (E9.5) with profound vascular defects in yolk sac embryo resembling the Galpha13 knockout phenotype. Furthermore, E8.5, embryos showed allantois...
Human blood is a self-regenerating lipid-rich biological fluid that routinely collected in hospital settings. The inventory of lipid molecules found plasma (plasma lipidome) offers insights into individual metabolism and physiology health disease. Disturbances the lipidome also occur conditions are not directly linked to metabolism; therefore, lipidomics based on MS an emerging tool array clinical diagnostics disease management. However, challenges exist translation such lipidomic data...
Abstract Background Regulation of lipid metabolism via activation sterol regulatory element binding proteins (SREBPs) has emerged as an important function the Akt/mTORC1 signaling axis. Although contribution dysregulated to cancer been investigated extensively and altered is observed in many tumors, exact role SREBPs control biosynthetic processes required for Akt-dependent cell growth their tumorigenesis remains unclear. Results We first effects loss SREBP non-transformed cells. Combined...
Enhanced macromolecule biosynthesis is integral to growth and proliferation of cancer cells. Lipid has been predicted be an essential process in However, it unclear which enzymes within this pathway offer the best selectivity for cells could suitable therapeutic targets. Using functional genomics, we identified stearoyl-CoA desaturase (SCD), enzyme that controls synthesis unsaturated fatty acids, as breast prostate SCD inhibition altered cellular lipid composition impeded cell viability...
Epidemiologic and genetic evidence links type 2 diabetes, obesity, cancer. The tumor-suppressor phosphatase tensin homologue (PTEN) has roles in both cellular growth metabolic signaling. Germline PTEN mutations cause a cancer-predisposition syndrome, providing an opportunity to study the effect of haploinsufficiency humans.
Dietary restriction (DR), a reduction in food intake without malnutrition, increases most aspects of health during aging and extends lifespan diverse species, including rodents. However, the mechanisms by which DR interacts with process to improve old age are poorly understood. DNA methylation could play an important role mediating effects because it is sensitive nutrition can affect gene expression memory over time. Here, we profile genome-wide changes methylation, lipidomics response...
Autophagy is a fundamental catabolic process that uses unique post-translational modification, the conjugation of ATG8 protein to phosphatidylethanolamine (PE). lipidation also occurs during non-canonical autophagy, parallel pathway involving single membranes (CASM) at endolysosomal compartments, with key functions in immunity, vision, and neurobiology. It widely assumed CASM involves same PE, but this has not been formally tested. Here, we discover all ATG8s can undergo alternative...
Colorectal cancer (CRC) is often diagnosed at a late stage with concomitant poor prognosis. Early detection greatly improves prognosis; however, the invasive, unpleasant and inconvenient nature of current diagnostic procedures limits their applicability. No serum-based test currently sufficient sensitivity or specificity for widespread use. In best available blood test, carcinoembryonic antigen exhibits low particularly in setting early disease. Hence, there great need new biomarkers CRC. We...