A5069366402- Cancer, Hypoxia, and Metabolism
- Epigenetics and DNA Methylation
- Peroxisome Proliferator-Activated Receptors
- RNA modifications and cancer
- Mitochondrial Function and Pathology
- Ion channel regulation and function
- Adipose Tissue and Metabolism
- Metabolism and Genetic Disorders
- Muscle activation and electromyography studies
- Biochemical Acid Research Studies
- Cardiovascular and exercise physiology
- Genomics, phytochemicals, and oxidative stress
- Biochemical and biochemical processes
- Microbial Metabolic Engineering and Bioproduction
University of Cambridge
2006-2023
Cambridge School
2020
Abstract 2-oxoglutarate (2-OG or α-ketoglutarate) relates mitochondrial metabolism to cell function by modulating the activity of 2-OG dependent dioxygenases involved in hypoxia response and DNA/histone modifications. However, metabolic pathways that regulate these oxygen sensitive enzymes remain poorly understood. Here, using CRISPR Cas9 genome-wide mutagenesis screen for genetic determinants levels, we uncover a redox lipoylation pathway, on hydrolase ABHD11, signals changes dioxygenase...
Cells produce considerable genotoxic formaldehyde from an unknown source. We carry out a genome-wide CRISPR-Cas9 genetic screen in metabolically engineered HAP1 cells that are auxotrophic for to find this cellular identify histone deacetylase 3 (HDAC3) as regulator of production. HDAC3 regulation requires activity, and secondary identifies several components mitochondrial complex I mediators regulation. Metabolic profiling indicates unexpected requirement detoxification is separate energy...
The combined effects of intracellular lactate and proton accumulation on cell volume, Vc, were investigated in resting Rana temporaria striated muscle fibres. Intracellular H+ concentrations simultaneously increased by exposing fibres to extracellular solutions that contained 20-80 mm sodium lactate. Cellular entry was confirmed using pH-sensitive electrodes 1H-NMR, respectively, Vc measured confocal microscope xz-scanning. Exposure up 80 produced significant changes pH (from a 7.24 +/-...
Abstract 2-oxoglutarate (2-OG or α-ketoglutarate) relates mitochondrial metabolism to cell function by modulating the activity of 2-OG dependent dioxygenases DDs) involved in hypoxia response and DNA/histone modifications. However, metabolic pathways that regulate these oxygen sensitive enzymes remain poorly understood. Here, using CRISPR Cas9 genome-wide mutagenesis screen for genetic determinants levels, we uncover a redox lipoylation pathway, on hydrolase ABHD11, signals changes DD...
Abstract Hypoxia-inducible transcription factors (HIFs) are fundamental to the cellular adaptation low oxygen levels but how they interact with chromatin and efficiently activate their target genes is unclear. Using genome-wide mutagenesis in human cancer cells, we define required for HIF transcriptional activation, identify a requirement Histone 3 lysine 4 (H3K4) methyltransferase SET1B. Loss of SET1B leads selective reduction activity hypoxia, driving expression involved angiogenesis...