A5008821485- Acute Myeloid Leukemia Research
- Protein Degradation and Inhibitors
- Cancer, Lipids, and Metabolism
- Receptor Mechanisms and Signaling
- Protein Kinase Regulation and GTPase Signaling
- Cellular transport and secretion
- Pancreatic function and diabetes
- Liver Disease Diagnosis and Treatment
- Lipid metabolism and biosynthesis
- Peroxisome Proliferator-Activated Receptors
- Metabolism and Genetic Disorders
- Biochemical and Molecular Research
- Peptidase Inhibition and Analysis
- Endoplasmic Reticulum Stress and Disease
- Pharmacogenetics and Drug Metabolism
- Diet and metabolism studies
- RNA modifications and cancer
- Extracellular vesicles in disease
- Ferroptosis and cancer prognosis
- Erythrocyte Function and Pathophysiology
- Chronic Lymphocytic Leukemia Research
- S100 Proteins and Annexins
- Amino Acid Enzymes and Metabolism
- HIV/AIDS drug development and treatment
- Advanced Proteomics Techniques and Applications
Queen Mary University of London
2021-2024
Cancer Institute (WIA)
2023
University of Sheffield
2017-2021
Protein S-acylation (palmitoylation) is a reversible lipid modification that an important regulator of dynamic membrane-protein interactions. Proteomic approaches have uncovered many putative palmitoylated proteins however, methods for comprehensive palmitoylation site characterization are lacking. We demonstrate quantitative site-specific-Acyl-Biotin-Exchange (ssABE) method allowed the identification 906 sites on 641 from mouse forebrain. 62% map to known and 102 individual literature. 54%...
Resistance to standard and novel therapies remains the main obstacle cure in acute myeloid leukaemia (AML) is often driven by metabolic adaptations which are therapeutically actionable. Here we identify inhibition of mannose-6-phosphate isomerase (MPI), first enzyme mannose metabolism pathway, as a sensitizer both cytarabine FLT3 inhibitors across multiple AML models. Mechanistically, connection between fatty acid metabolism, that mediated via preferential activation ATF6 arm unfolded...
Abstract Identification of specific and therapeutically actionable vulnerabilities, ideally present across multiple mutational backgrounds, is needed to improve acute myeloid leukemia (AML) patients’ outcomes. We identify stearoyl-CoA desaturase (SCD), the key enzyme in fatty acid (FA) desaturation, as prognostic patients' outcomes and, using clinical-grade inhibitor SSI-4, show that SCD inhibition (SCDi) a therapeutic vulnerability AML models vitro vivo. Multiomic analysis demonstrates SCDi...
Abstract Identification of specific and therapeutically actionable vulnerabilities in acute myeloid leukaemia (AML) is needed to improve patients’ outcome. These features should be ideally present many patients independently mutational background. Here we identify de novo fatty acid (FA) desaturation, specifically stearoyl-CoA desaturase (SCD) inhibition, as a therapeutic vulnerability across multiple AML models vitro vivo . We use the novel clinical grade SCD inhibitor SSI-4 show that...
Abstract S-acylation is the only fully reversible lipid modification of proteins however little known about how protein S-acyltransferases (PATs) that mediate it are regulated. DHHC5 a plasma membrane-localised PAT with roles in synaptic plasticity, massive endocytosis and cancer cell growth/invasion. Here we demonstrate stabilisation at membrane requires binding to palmitoylation an accessory Golga7b. This interaction C-terminus which regulates internalisation from membrane. Proteomic...
Abstract Resistance to standard and novel therapies remains the main obstacle cure in acute myeloid leukemia (AML) is often driven by metabolic adaptations which are therapeutically actionable. Here we identify inhibition of mannose-6-phosphate isomerase (MPI), first enzyme mannose metabolism pathway, as a sensitizer both cytarabine FLT3 inhibitors across multiple AML models. Mechanistically, connection between fatty acid metabolism, that mediated via preferential activation ATF6 arm...