A5064470685- Redox biology and oxidative stress
- Acute Lymphoblastic Leukemia research
- Heat shock proteins research
- Neonatal Health and Biochemistry
- Photosynthetic Processes and Mechanisms
- Peptidase Inhibition and Analysis
- VLSI and Analog Circuit Testing
- Cancer, Hypoxia, and Metabolism
- Cancer-related gene regulation
- Genetic and Kidney Cyst Diseases
- Osteoarthritis Treatment and Mechanisms
- Blood disorders and treatments
- Integrated Circuits and Semiconductor Failure Analysis
- Genomics, phytochemicals, and oxidative stress
- CAR-T cell therapy research
- Chronic Myeloid Leukemia Treatments
- Cancer Treatment and Pharmacology
- Cancer-related molecular mechanisms research
- Medical Imaging Techniques and Applications
- Phytochemical compounds biological activities
- Fungal and yeast genetics research
- Microtubule and mitosis dynamics
- PARP inhibition in cancer therapy
- RNA regulation and disease
- Histone Deacetylase Inhibitors Research
Newcastle University
2012-2024
Newcastle upon Tyne Hospital
2014
Osteoarthritis is a degenerative joint disease characterized by progressive and irreversible loss of the articular cartilage, due in main part to cleavage type II collagen within matrix enzyme metalloproteinase (MMP)13. Here, we examined methylation status MMP13 promoter report demethylation specific CpG dinucleotides its osteoarthritic compared normal which correlates with increased expression. Of sites examined, –104 was consistently demethylated following treatment human chondrocytes 10μM...
Reactive oxygen species (ROS) are physiological mediators of cellular signaling and play potentially damaging roles in human diseases. In this study, we found that the catalytic activity Ser/Thr kinase Aurora A was inhibited by oxidation a conserved cysteine residue (Cys
Peroxiredoxins (Prdxs) utilize reversibly oxidized cysteine residues to reduce peroxides and promote H2O2 signal transduction, including H2O2-induced activation of P38 MAPK. Prdxs form disulfide complexes with many proteins, multiple kinases involved in MAPK signaling. Here, we show that a genetically encoded fusion between Prdx is sufficient hyperactivate the kinase yeast human cells by mechanism does not require H2O2-sensing Prdx. We demonstrate P38-Prdx protein compensates for loss...
Due to the rarity of TP53 mutations in acute lymphoblastic leukemia (ALL), p53 re-activation by antagonism p53-MDM2 interaction represents a potential therapeutic strategy for majority ALL. Here, we demonstrate potent antileukemic activity MDM2 antagonist idasanutlin high-risk and relapsed ex vivo coculture models wildtype ALL (n = 40). Insufficient clinical responses monotherapy inhibitors other cancers prompted us explore optimal drugs combination therapy. Utilizing high-throughput...
Abstract Elevated pro-inflammatory signalling coupled with catabolic metalloproteinase expression is a common feature of arthritis, leading to cartilage damage, deterioration the joint architecture and associated pain immobility. Countering these processes, histone deacetylase inhibitors (HDACi) have been shown suppress matrix (MMP) expression, block cytokine-induced reduce degradation in animal models arthritis. In order establish which specific HDACs account for chondro-protective effects...
Poly(adenosine diphosphate ribose) polymerases (PARPs) are multifunctional proteins which play a role in many cellular processes. Namely, PARP1 and PARP2 have been shown to be involved DNA repair, therefore valid targets cancer treatment with PARP inhibitors, such as rucaparib, currently clinical trials. Proton magnetic resonance spectroscopy ( 1 H‐MRS) was used study the impact of rucaparib vitro ex vivo liver tissue from mice, via quantitative analysis nicotinamide adenosine (NAD + )...
Dubin-Johnson syndrome is a rare benign autosomal recessive condition that causes an isolated increase of conjugated bilirubin in the serum. Impaired biliary excretion due to mutation multiple drug-resistance protein 2 gene (MRP2).We describe case 4-year-old girl being treated for acute lymphoblastic leukaemia who had history hyperbilirubinaemia and persistently elevated levels on initiation chemotherapy. During treatment leukaemia, she was diagnosed with underlying condition. Following...
The <italic>de novo</italic> synthesis of 3′-deoxy-3′-fluorothymidine-5′-<italic>O</italic>-glucuronide enabled both the analysis this reference standard by HPLC and identification metabolite in a blood sample from patient administered [<sup>18</sup>F]FLT.
Summary Peroxiredoxins (Prdx) utilize reversibly oxidized cysteine residues to reduce peroxides but also promote H 2 O signal transduction, including -induced activation of P38 MAPK. Prdx form disulfide complexes with many proteins, multiple kinases involved in MAPK signaling. Here we show that a genetically-encoded fusion between and the is sufficient hyperactivate kinase yeast human cells by mechanism does not require -sensing Prdx. In yeast, demonstrate P38-Prdx protein compensates for...
In order to protect against oxidative damage, cells have evolved a host of ROS-detoxifying enzymes. These include peroxiredoxins, highly conserved family thioredoxin peroxidases. Unexpectedly, given their role in lowering H2O2levels, peroxiredoxins been shown be required for the activation stress-activated MAPKs response ROS yeast1 and human2 cells. For example, we previously that single 2-Cys peroxiredoxin S. pombe , Tpx1, but not its peroxidase activity, is H2O2-induced p38/JNK-related...