A5003583446- Cancer, Hypoxia, and Metabolism
- Cancer, Lipids, and Metabolism
- RNA modifications and cancer
- Autophagy in Disease and Therapy
- Epigenetics and DNA Methylation
- Cancer-related Molecular Pathways
- Ferroptosis and cancer prognosis
- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Glioma Diagnosis and Treatment
- Pregnancy and preeclampsia studies
- Metabolism, Diabetes, and Cancer
- Cancer Cells and Metastasis
- Erythrocyte Function and Pathophysiology
- Amino Acid Enzymes and Metabolism
- Vitamin C and Antioxidants Research
- Mesenchymal stem cell research
- Acute Myeloid Leukemia Research
- Ubiquitin and proteasome pathways
- Prion Diseases and Protein Misfolding
- Prenatal Screening and Diagnostics
- Endoplasmic Reticulum Stress and Disease
Cancer Research UK
2021-2024
Cancer Research UK Scotland Institute
2021-2023
STCube (United States)
2023
National Institute of Immunology
2017-2019
National Institute of Pharmaceutical Education and Research
2012
The metabolic changes controlling the stepwise differentiation of hematopoietic stem and progenitor cells (HSPCs) to mature erythrocytes are poorly understood. Here, we show that HSPC development an erythroid-committed proerythroblast results in augmented glutaminolysis, generating alpha-ketoglutarate (αKG) driving mitochondrial oxidative phosphorylation (OXPHOS). However, sequential late-stage erythropoiesis is dependent on decreasing αKG-driven OXPHOS, find isocitrate dehydrogenase 1...
Caspase-10 belongs to the class of initiator caspases and is a close homolog caspase-8. However, lack caspase-10 in mice limited substrate repertoire restricts understanding its physiological functions. Here, we report that ATP-citrate lyase (ACLY) substrate. cleaves ACLY at conserved Asp1026 site under conditions altered metabolic homeostasis. Cleavage abrogates enzymatic activity suppresses generation acetyl-CoA, which critical for lipogenesis histone acetylation. Thus, caspase-10-mediated...
Although protein synthesis inhibitors are being evaluated as anti-cancer agents, the dynamics of mRNA translation in early tumorigenesis still poorly understood. We report that deletion mRNA-translation repressor, eIF4A2 KRAS-driven lung adenocarcinoma leads to a dysregulated landscape characterised by strongly upregulated secretome, enlarged secretory compartments, increased oxidative metabolism and acquisition senescence-like characteristics. Paradoxically, this overdriven delays...
Cyclin F is a substrate recognition subunit of Skp1-Cul1-F-box protein (SCF) E3 ubiquitin ligase complex. Although there have been reports describing the role cyclin in genotoxic stress response, its function under conditions altered metabolic homeostasis remain unexplored. Here we report that induced upon FOXO1-dependent manner. Under conditions, mediated polyubiquitylation RBPJ at Lys315, leading to proteasomal degradation. regulated expression IDH1, which often mutated an oncogenic form...
Glutamine synthetase (GS) activity is conserved from prokaryotes to humans, where the ATP-dependent production of glutamine glutamate and ammonia essential for neurotransmission detoxification. Here, we show that mammalian GS uses methylamine produce a methylated analog, N
Human trophoblast cultures provide powerful tools to model key processes of placental development. In vitro studies date have relied on commercial media that contains nonphysiological levels nutrients, and the impact these conditions metabolism function is unknown. Here, we show physiological medium (Plasmax) with nutrient metabolite concentrations recapitulating human plasma improves stem cell (hTSC) proliferation differentiation compared standard (DMEM-F12). hTSCs cultured in Plasmax-based...
Bone marrow mesenchymal stromal cells (MSCs) have immunomodulatory and regenerative potential. However, culture conditions govern their metabolic processes therapeutic efficacy. Here we show that culturing donor-derived MSCs in Plasmax™, a physiological medium with the concentrations of nutrients found human plasma, supports proliferation stemness, prevents nutritional stress induced by conventional DMEM. The quantification exchange rates metabolites between medium, untargeted metabolomics,...
Abstract The limited availability of therapeutic options for patients with triple-negative breast cancer (TNBC) contributes to the high rate metastatic recurrence and poor prognosis. Ferroptosis is a type cell death caused by iron-dependent lipid peroxidation counteracted antioxidant activity selenoprotein GPX4. Here, we show that TNBC cells secrete an anti-ferroptotic factor in extracellular environment when cultured at densities but are primed ferroptosis forming colonies low density. We...