A5033773451- DNA Repair Mechanisms
- Genetic factors in colorectal cancer
- Cancer Genomics and Diagnostics
- Sexual function and dysfunction studies
- PARP inhibition in cancer therapy
- Sexual Differentiation and Disorders
- Protein Degradation and Inhibitors
- Multiple Myeloma Research and Treatments
- RNA modifications and cancer
- Cancer Research and Treatments
- RNA Research and Splicing
- Liver Disease Diagnosis and Treatment
- CRISPR and Genetic Engineering
- Metabolomics and Mass Spectrometry Studies
- Lung Cancer Treatments and Mutations
- Virus-based gene therapy research
- Cancer, Hypoxia, and Metabolism
- Urological Disorders and Treatments
- Cancer-related Molecular Pathways
- Caveolin-1 and cellular processes
- Epigenetics and DNA Methylation
- HIV/AIDS drug development and treatment
- Mitochondrial Function and Pathology
- Pancreatic and Hepatic Oncology Research
- Cancer, Lipids, and Metabolism
Queen Mary University of London
2012-2024
University of Illinois Chicago
2021-2024
University of Saskatchewan
2019-2023
Cancer Research UK
2009-2023
John Wiley & Sons (United States)
2023
IFB Adiposity Diseases
2022
Leipzig University
2022
Lurie Children's Hospital
2021
Broadata Communications (United States)
2021
The University of Texas Southwestern Medical Center
2018-2020
Synthetic sickness/lethality (SSL) can be exploited to develop therapeutic strategies for cancer. Deficiencies in the tumor suppressor proteins MLH1 and MSH2 have been implicated Here we demonstrate that deficiency is SSL with inhibition of DNA polymerase POLB, whereas POLG inhibition. Both SSLs led accumulation 8-oxoG oxidative lesions. MSH2/POLB caused nuclear accumulation, MLH1/POLG a rise mitochondrial levels. were rescued by silencing adenine glycosylase MUTYH, suggesting lethality...
Research Article28 September 2009Open Access Methotrexate induces oxidative DNA damage and is selectively lethal to tumour cells with defects in the mismatch repair gene MSH2 Sarah A. Martin Cancer UK Gene Function Regulation Group, The Breakthrough Breast Centre, Institute of Research, London, Search for more papers by this author Afshan McCarthy Louise J. Barber Darren Burgess Suzanne Parry Christopher Lord Corresponding Author [email protected] Alan Ashworth Information Martin1,2,...
Genes encoding the histone H3 lysine 4 methyltransferases KMT2C and KMT2D are subject to deletion mutation in pancreatic ductal adenocarcinoma (PDAC), where these lesions identify a group of patients with more favorable prognosis. In this study, we demonstrate that low expression biopsies also defines better outcome groups, median survivals 15.9 versus 9.2 months (P = 0.029) 19.9 11.8 0.001), respectively. Experiments eight human cell lines showed attenuated proliferation when were depleted,...
Substitution of lysine for glutamic acid at residu 167 in Transmembrane 6 superfamily member 2 (TM6SF2) is associated with fatty liver disease and reduced plasma lipid levels. Tm6sf2-/- mice replicate the human phenotype but were not suitable detailed mechanistic studies. As an alternative model, we generated rats to determine subcellular location function TM6SF2.Two lines established using gene editing. Lipids from tissues newly secreted very low density lipoproteins (VLDLs) quantified...
Synthetic lethal approaches to cancer treatment have the potential deliver relatively large therapeutic windows and therefore significant patient benefit. To identify for cancers deficient in DNA mismatch repair (MMR), we carried out parallel high-throughput RNA interference screens using tumor cell models of MSH2- MLH1-related MMR deficiency. We show that silencing PTEN-induced putative kinase 1 (PINK1), is synthetically with deficiency cells MSH2, MLH1, or MSH6 dysfunction. Inhibition...
An unbiased sample preparation free of interferents (i.e., competing analytes, detergents, plastics) is critical to any lipid MS workflow. Here we present a novel three-phase extraction (3PLE) technique using single-step liquid-liquid (LLE) that allows both and fractionation lipids by polarity. 3PLE composed one aqueous two organic phases. The upper phase enriched in neutral (triacylglycerols cholesteryl esters), while the middle contains major glycerophospholipids. Thin-layer...
The antidiabetic potential of glucagon receptor antagonism presents an opportunity for use in insulin-centric clinical environment. To investigate the metabolic effects type 2 diabetes, we treated Leprdb/db and Lepob/ob mice with REMD 2.59, a human monoclonal antibody competitive antagonist receptor. As expected, 2.59 suppresses hepatic glucose production improves glycemia. Surprisingly, it also enhances insulin action both liver skeletal muscle, coinciding increase AMP-activated protein...
Argininosuccinate synthase 1 (ASS1) is the rate-limiting enzyme for arginine biosynthesis. ASS1 expression lost in a range of tumor types, including 50% malignant pleural mesotheliomas. Starving ASS1-deficient cells with blockers such as ADI-PEG20 can induce selective lethality and has shown great promise clinical setting. We have generated model resistance mesothelioma cells. This mediated through re-expression via demethylation promoter. Through coordinated transcriptomic metabolomic...
Abstract Background Many patients with locally advanced gastro-oesophageal cancers are unable to complete adjuvant 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy, raising questions about its therapeutic utility. The aim of this study was examine whether pathological response neoadjuvant FLOT can guide use. Methods Patients non-metastatic adenocarcinoma who received underwent surgery from 1 January 2017 2022 43 hospitals across 12 countries were analysed....
Long-chain acyl-CoA synthetase 1 (ACSL1) contributes more than 90% of total cardiac ACSL activity, but its role in phospholipid synthesis has not been determined. Mice with an inducible knockout ACSL1 (Acsl1(T-/-)) have impaired fatty acid oxidation and rely on glucose for ATP production. Because exhibited a strong substrate preference linoleate, we investigated the composition heart phospholipids. Acsl1(T-/-) hearts contained 83% less tetralinoleoyl-cardiolipin (CL), major form present...
The differentiation of resident tissue macrophages from embryonic precursors and that inflammatory bone marrow cells leads to macrophage heterogeneity. Further plasticity is displayed through their ability be polarized as subtypes M1 M2 in a cell culture microenvironment. However, the detailed regulation eicosanoid production its involvement biology remains unclear. Using lipidomics approach, we demonstrated profiles between marrow-derived (BMDM) peritoneal differed drastically. In BMDMs,...
Abstract The DNA mismatch repair (MMR) pathway is responsible for the of base–base mismatches and insertion/deletion loops that arise during replication. MMR deficiency currently estimated to be present in 15–17% colorectal cancer cases 30% endometrial cancers. MLH1 one key proteins involved pathway. Inhibition a number mitochondrial genes, including POLG PINK1 can induce synthetic lethality MLH1-deficient cells. Here we demonstrate first time loss associated with deregulated metabolism,...
Mutations in the tumor suppressor gene Adenomatous Polyposis Coli (APC) are found 80% of sporadic colorectal cancer (CRC) tumors and also responsible for inherited form CRC, Familial adenomatous polyposis (FAP).To identify novel therapeutic strategies treatment APC mutated we generated a drug screening platform that incorporates human cellular model mutant CRC using CRISPR-cas9 editing performed an FDA-approved screen targeting over 1000 compounds.We have identified group HMG-CoA Reductase...