A5018889463- Tuberculosis Research and Epidemiology
- Biochemical and Molecular Research
- Cancer, Hypoxia, and Metabolism
- Immune cells in cancer
- Epigenetics and DNA Methylation
- HIV/AIDS drug development and treatment
- Mycobacterium research and diagnosis
- Angiogenesis and VEGF in Cancer
- Venous Thromboembolism Diagnosis and Management
- Enzyme Structure and Function
- Immune Cell Function and Interaction
- Marine Sponges and Natural Products
- PI3K/AKT/mTOR signaling in cancer
- Synthesis and Characterization of Heterocyclic Compounds
- Microbial Natural Products and Biosynthesis
- Radiomics and Machine Learning in Medical Imaging
- Histone Deacetylase Inhibitors Research
- Lung Cancer Diagnosis and Treatment
- Chemical Synthesis and Analysis
- Lung Cancer Treatments and Mutations
- T-cell and B-cell Immunology
- Synthesis and biological activity
- High Altitude and Hypoxia
- Pneumocystis jirovecii pneumonia detection and treatment
- Cancer Mechanisms and Therapy
University of Cambridge
2011-2023
CIC bioGUNE
2022
Ikerbasque
2022
Cancer Research UK Cambridge Center
2017-2018
Cancer Research UK
2017
Cytotoxic T cells infiltrating tumors are thought to utilize HIF transcription factors during adaptation the hypoxic tumor microenvironment. Deletion analyses of two key isoforms found that HIF-1α, but not HIF-2α, was essential for effector state in CD8+ cells. Furthermore, loss HIF-1α reduced infiltration and cell killing, altered vascularization. VEGF-A, an target gene, accelerated tumorigenesis while also altering Analyses human breast cancer showed inverse correlations between VEGF-A...
Fumarate hydratase (FH) is an enzyme of the tricarboxylic acid (TCA) cycle mutated in hereditary and sporadic cancers. Despite recent advances understanding its role tumorigenesis, effects FH loss on mitochondrial metabolism are still unclear. Here, we used mouse human cell lines to assess function FH-deficient cells. We found that cells exhibit decreased respiration, accompanied by a varying degree dysfunction respiratory chain (RC) complex I II. Moreover, show fumarate induces succination...
Animals require an immediate response to oxygen availability allow rapid shifts between oxidative and glycolytic metabolism. These metabolic are highly regulated by the HIF transcription factor. The factor inhibiting (FIH) is asparaginyl hydroxylase that controls transcriptional activity in oxygen-dependent manner. We show here FIH loss increases metabolism, while also increasing capacity, this gives rise increase consumption. further of acts accelerate cellular hypoxia. Skeletal muscle...
Say "when": Analysis of the biosynthetic gene cluster for polyether antibiotic and anticancer agent salinomycin (1) shows that its core structure is synthesised by a nine-multienzyme modular polyketide synthase. Deletion salC gene, which required oxidative cyclisation, has led to detection novel metabolite whose reveals timing key dehydration step. Detailed facts importance specialist readers are published as "Supporting Information". Such documents peer-reviewed, but not copy-edited or...
Dihydrofolate reductase (DHFR), a key enzyme involved in folate metabolism, is widely explored target the treatment of cancer, immune diseases, bacteria, and protozoa infections. Although several antifolates have proved successful infectious they been underexplored to combat tuberculosis, despite essentiality M. tuberculosis DHFR (MtDHFR). Herein, we describe an integrated fragment-based drug discovery approach MtDHFR that has identified hits with scaffolds not yet any previous design...
2-Hydroxyglutarate (2HG) is a byproduct of the tricarboxylic acid (TCA) cycle and readily detected in tissues healthy individuals. 2HG found two enantiomeric forms: S-2HG R-2HG. Here, we investigate differential roles these enantiomers cluster differentiation (CD)8+ T cell biology, where find they have highly divergent effects on proliferation, differentiation, function. We show here an analysis structural determinants that likely underlie specific α-ketoglutarate (αKG)-dependent enzymes....
Thrombosis can cause localized ischemia and tissue hypoxia, both of these are linked to cancer metastasis. Vascular micro-occlusion occur as a result arrest circulating tumour cells in small capillaries, giving rise microthrombotic events that affect flow, creating hypoxic regions. To better understand the association between metastasis thrombotic events, we generated an experimental strategy whereby modelled effect microvascular occlusion metastatic efficiency by using inert microbeads...
e15134 Background: Despite high mutation rates in genes of the PI3K/mTOR/AKT pathway cancer, therapeutic strategies to inhibit this featuring single targeted therapies have achieved limited clinical success. An alternate approach inhibiting multiple parts simultaneously demonstrated improved activity (Starks et al, GynOnc 2022). The Phase 1 study combined PI3K-alpha and mTOR inhibitors serabelisib sapanisertib (PIKTOR) with paclitaxel showing reasonable safety promising efficacy patients...
Abstract Dihydrofolate reductase (DHFR), a key enzyme involved in folate metabolism, is widely explored target the treatment of cancer, immune diseases, bacteria and protozoa infections. Although several antifolates have proved successful infectious none been developed to combat tuberculosis, despite essentiality M. tuberculosis DHFR (MtDHFR). Herein, we describe an integrated fragment-based drug discovery approach MtDHFR that has identified hits with scaffolds not yet any previous design...
SUMMARY 2-hydroxyglutarate (2HG) is a by-product of the TCA cycle, and readily detected in tissues healthy individuals. 2HG found two enantiomeric forms: S-2HG R-2HG. Here, we investigate differential roles these enantiomers CD8+ T cell biology, where they had highly divergent effects on proliferation, differentiation, function. We show here an analysis structural determinants that likely underlie specific a-ketoglutarate (aKG)-dependent enzymes. Treatment cells with exogenous S-2HG, but not...
Introduction: Mechanisms that regulate the positive association between thrombosis and metastasis are incompletely understood. It was hypothesised thrombus formation stimulates a hypoxic response, which in turn promotes extravasation. The primary aim to determine whether of pulmonary microvasculature (T pm ) increases extravasation via myeloid (neutrophil macrophage) hypoxia-inducible factor (HIF). Methods Results: T induced wild type mice tail vein administration polystyrene microbeads...
Abstract Thrombosis causes local blood flow restriction and tissue hypoxia, both of these are associated with tumor cell metastasis. To better understand the regulation thrombosis-induced metastasis, we created a model incorporating elements processes. Controlled induction pulmonary microthrombosis caused an increase in expression first hypoxia-inducible factor (HIF)1α, subsequently HIF2α. Induction thrombosis before introduction cells to venous circulation had no effect on number or size;...