A5090043619- Platelet Disorders and Treatments
- PI3K/AKT/mTOR signaling in cancer
- Chronic Lymphocytic Leukemia Research
- Cellular transport and secretion
- Protein Kinase Regulation and GTPase Signaling
- Cell Adhesion Molecules Research
- Lipid metabolism and biosynthesis
- Blood properties and coagulation
- Blood groups and transfusion
- Protein Tyrosine Phosphatases
- Chemotherapy-induced cardiotoxicity and mitigation
- Erythrocyte Function and Pathophysiology
- Liver Disease Diagnosis and Treatment
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Heparin-Induced Thrombocytopenia and Thrombosis
- Lipid Membrane Structure and Behavior
- Alcohol Consumption and Health Effects
- Lysosomal Storage Disorders Research
- Antiplatelet Therapy and Cardiovascular Diseases
- Hepatitis B Virus Studies
Novo Nordisk (United Kingdom)
2023
University of Bristol
2016-2020
University of Oxford
2018-2020
Babraham Institute
2013
•Genetically predicted increases in MTARC1 mRNA associate with poor liver health.•mARC1 knockdown decreases lipid accumulation primary human hepatocytes.•Hepatocyte-specific of mARC1 improves steatosis a murine NASH model. Background & AimsNon-alcoholic fatty disease (NAFLD) has prevalence ∼25% worldwide, significant public health consequences yet few effective treatments. Human genetics can help elucidate novel biology and identify targets for new therapeutics. Genetic variants...
We disrupted the gene encoding lysophosphatidylinositol-acyltransferase-1 (LPIAT1) in mouse with aim of understanding its role determining cellular phosphoinositide content. LPIAT1−/− mice were born at lower than Mendelian ratios and exhibited a severe developmental brain defect. compared phospholipid content livers brains from LPIAT1+/+ littermates by LC-ESI/MS. In accord previous studies, most abundant molecular species each class (PtdIns, PtdInsP, PtdInsP2 PtdInsP3) possessed C38∶4...
Class IA PI3Ks have many roles in health and disease. The rules that govern intersubunit receptor associations, however, remain unclear. We engineered mouse lines which individual endogenous class PI3K subunits were C-terminally tagged with 17aa could be biotinylated vivo. Using these tools we quantified streptavidin or PDGFR pull-downs cell lysates. This revealed p85α β bound equivalently to p110α p110β but preferentially p110δ. p85s found molar-excess over p110s a number of contexts...
Key Points We present the first in-depth analysis of platelet PtdIns(3,4,5)P3-binding proteins, providing a valuable resource for future studies. The protein, DAPP1, negatively regulates glycoprotein VI–driven activation and thrombus formation.
Abstract Thrombopoietin (TPO) enhances platelet activation through of the tyrosine kinase; JAK2 and lipid kinase phosphatidylinositide 3-kinase (PI3K). The aim our study was to identify PI3K isoforms involved in mediating effect TPO on function elucidate underlying mechanism. We found that p110β plays an essential role TPO-mediated (i) priming protease-activated receptor (PAR)-mediated integrin α IIb β 3 α-granule secretion, (ii) synergistic enhancement PAR-mediated small GTPase RAP1, a...