A5073672082- Cancer, Hypoxia, and Metabolism
- Prostate Cancer Treatment and Research
- Cancer, Lipids, and Metabolism
- Tryptophan and brain disorders
- Stress Responses and Cortisol
- PARP inhibition in cancer therapy
- Receptor Mechanisms and Signaling
- Metabolism, Diabetes, and Cancer
- Mass Spectrometry Techniques and Applications
- Amino Acid Enzymes and Metabolism
- Epigenetics and DNA Methylation
- Metabolomics and Mass Spectrometry Studies
- Muscle metabolism and nutrition
- Ovarian cancer diagnosis and treatment
- Cancer-related Molecular Pathways
- Pancreatic and Hepatic Oncology Research
- Lipoproteins and Cardiovascular Health
- Reproductive Biology and Fertility
- Endoplasmic Reticulum Stress and Disease
- Advanced Proteomics Techniques and Applications
- Adenosine and Purinergic Signaling
- Biochemical and Molecular Research
- Genetic Neurodegenerative Diseases
- Ovarian function and disorders
- Microtubule and mitosis dynamics
Cancer Research UK
2013-2024
Cancer Research UK Scotland Institute
2014-2023
University of California, San Diego
2023
University of Glasgow
2004-2020
University Hospital of Basel
2018-2019
University of Basel
2019
Institute of Social Work
2017
Switch
2017
University of Oklahoma Health Sciences Center
2015-2017
Olive View-UCLA Medical Center
2015
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...
Previous work has shown that some cancer cells are highly dependent on serine/glycine uptake for proliferation. Although serine and glycine can be interconverted either might used nucleotide synthesis one-carbon metabolism, we show exogenous cannot replace to support cell Cancer selectively consumed serine, which was converted intracellular units building nucleotides. Restriction of or depletion the cleavage system did not impede In absence unable synthesis. Indeed, higher concentrations...
Plasmax, a physiological cell culture medium, prevents metabolic artifacts imposed on cancer cells by commonly used media.
Acetyl-CoA is a key metabolic intermediate with an important role in transcriptional regulation. The nuclear-cytosolic acetyl-CoA synthetase 2 (ACSS2) was found to sustain the growth of hypoxic tumor cells. It generates from acetate, but exactly which pathways it supports not fully understood. Here, quantitative analysis acetate metabolism reveals that ACSS2 fulfills distinct functions depending on its cellular location. Exogenous uptake controlled by expression both and mitochondrial ACSS1,...
Abstract Despite the clinical success of Androgen Receptor (AR)-targeted therapies, reactivation AR signalling remains main driver castration-resistant prostate cancer (CRPC) progression. In this study, we perform a comprehensive unbiased characterisation LNCaP cells chronically exposed to multiple inhibitors (ARI). Combined proteomics and metabolomics analyses implicate an acquired metabolic phenotype common in ARI-resistant associated with perturbed glucose lipid metabolism. To exploit...
Abstract Abnormalities in the kynurenine pathway may play a role Huntington's disease (HD). In this study, tryptophan depletion and loading were used to investigate changes blood metabolites, as well markers of inflammation oxidative stress HD patients healthy controls. Results showed that : ratio was greater than controls baseline state after depletion, indicating increased indoleamine dioxygenase activity HD. Evidence for persistent provided by elevated levels C‐reactive protein, neopterin...
Serine catabolism results in formate efflux that exceeds anabolic demands for purine synthesis.
Of the major components of kynurenine pathway for oxidative metabolism tryptophan, most attention has focussed on N-methyl-D-aspartate (NMDA) receptor agonist quinolinic acid, and glutamate blocker kynurenic acid. However, there is increasing evidence that redox-active compound 3-hydroxyanthranilic acid may also have potent actions cell function in nervous immune systems, recent clinical data show marked changes levels this compound, associated with anthranilic levels, patients a range...
Chemotaxis is fundamentally important, but the sources of gradients in vivo are rarely well understood. Here, we analyse self-generated chemotaxis, which cells respond to they have made themselves by breaking down globally available attractants, using both computational simulations and experiments. We show that chemoattractant degradation creates steep local gradients. This leads surprising results, particular existence a leading population moves highly directionally, while behind this group...
Endothelial cells (ECs) play a key role to maintain the functionality of blood vessels. Altered EC permeability causes severe impairment in vessel stability and is hallmark pathologies such as cancer thrombosis. Integrating label-free quantitative proteomics data into genome-wide metabolic modeling, we built up model that predicts fluxes ECs when cultured on tridimensional matrix organize vascular-like network. We discovered how fatty acid oxidation increases are assembled fully formed...
Abstract Formate overflow coupled to mitochondrial oxidative metabolism\ has been observed in cancer cell lines, but whether that takes place the tumor microenvironment is not known. Here we report observation of serine catabolism formate normal murine tissues, with a relative rate correlating levels and tissue state. Yet, increased transformed vivo models intestinal adenomas mammary carcinomas. The associated serum levels. Finally, show inhibition production by genetic interference reduces...
Abstract BH3-mimetics are a new class of anti-cancer drugs that inhibit anti-apoptotic Bcl-2 proteins. In doing so, sensitise to cell death. Venetoclax is potent, BCL-2 selective BH3-mimetic clinically approved for use in chronic lymphocytic leukaemia. has also been shown mitochondrial metabolism, this consistent with proposed role metabolic regulation. We used venetoclax understand function. Similar others, we found inhibited respiration. addition, impairs TCA cycle activity leading...
Cellular senescence is not only associated with ageing but also impacts physiological and pathological processes, such as embryonic development wound healing. Factors secreted by senescent cells affect their microenvironment can induce spreading of locally. Acute severe liver disease hepatocyte frequently progresses to multi-organ failure. Why the latter occurs poorly understood. Here we demonstrate in extrahepatic organs organ dysfunction response using injury models genetic...
Abstract Inflammation and oxidative stress are involved in brain damage following stroke, tryptophan oxidation along the kynurenine pathway contributes to modulation of partly via glutamate receptor agonist quinolinic acid antagonist kynurenic acid, redox‐active compounds such as 3‐hydroxyanthranilic acid. We have confirmed that a patients show early elevations plasma neopterin, S100B peroxidation markers, latter two correlating with infarct volume assessed from computed tomography (CT)...
The kynurenine pathway generates the excitotoxic N ‐methyl‐ d ‐aspartate receptor agonist, quinolinic acid and glutamate antagonist, kynurenic acid, as well free‐radical generators. We investigated status of following severe brain injury sustained at least 1 year previously in 15 patients compared with controls. At baseline, showed increased levels neopterin, erythrocyte sedimentation rate, C‐reactive protein peroxidation products blood controls, indicating persistent inflammation oxidative...
Abstract The role of glutaminolysis in providing metabolites to support tumour growth is well-established, but the involvement glutamine metabolism invasive processes yet be elucidated. Here we show that normal mammary epithelial cells consume glutamine, do not secrete glutamate. Indeed, low levels extracellular glutamate are necessary maintain homoeostasis, and provision drives disruption morphology promotes key characteristics phenotype such as lumen-filling basement membrane disruption....