A5089543020- Mitochondrial Function and Pathology
- Birth, Development, and Health
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Cell death mechanisms and regulation
- Renal and related cancers
- Autophagy in Disease and Therapy
- Cancer, Hypoxia, and Metabolism
- Congenital heart defects research
- DNA and Nucleic Acid Chemistry
- Cardiac, Anesthesia and Surgical Outcomes
- Parkinson's Disease Mechanisms and Treatments
- Neuroblastoma Research and Treatments
- Musculoskeletal synovial abnormalities and treatments
- Genetics, Aging, and Longevity in Model Organisms
- Viral Infections and Immunology Research
- Heat shock proteins research
- DNA Repair Mechanisms
- Energetic Materials and Combustion
- Metabolism and Genetic Disorders
- Clostridium difficile and Clostridium perfringens research
- Retinoids in leukemia and cellular processes
- Cellular transport and secretion
- Soft tissue tumors and treatment
- Brain Metastases and Treatment
University of Manchester
2024
Cancer Research UK Manchester Institute
2024
University of Cambridge
2002-2023
Indiana University School of Medicine
2008-2020
Indiana University
2020
University of South Florida
2019
University of Colorado Anschutz Medical Campus
2018
University of Colorado Denver
2018
Indiana University – Purdue University Indianapolis
2008-2015
Monash University
2005-2012
Hypoxia is a common feature of solid tumours affecting their biology and response to therapy. One the main transcription factors activated by hypoxia hypoxia-inducible factor (HIF), which regulates expression genes involved in various aspects tumourigenesis including proliferative capacity, angiogenesis, immune evasion, metabolic reprogramming, extracellular matrix (ECM) remodelling, cell migration. This can negatively impact patient outcomes inducing therapeutic resistance. The importance...
A high yield, photoactivated cross-linking reaction between a modified tRNA and RNase P RNA was used as quantitative assay of substrate binding affinity. The allows the effects metal ions on to be measured independently in absence pre-tRNA cleavage reaction. results this assay, conjunction with conventional support following conclusions about nature RNA-tRNA interaction. (i) Monovalent cations act primarily enhance enzyme-substrate binding, presumably by functioning counterions. This...
Programmed necrosis is a mechanism of cell death that has been described for neuronal excitotoxicity and ischemia/reperfusion injury, but not extensively studied in the context exposure to bacterial exotoxins. The alpha-toxin Clostridium septicum beta-barrel pore-forming toxin potent cytotoxin; however, by which it induces elucidated detail. We report formed Ca(2+)-permeable pores murine myoblast cells, leading an increase intracellular Ca(2+) levels. This influx did induce apoptosis, as...
Low-level vancomycin resistance in Staphylococcus aureus (vancomycin-intermediate S. (VISA) and hetero-VISA [hVISA]) emerges during persistent infection failed therapy. Up-regulation of genes associated with the "cell wall stimulon" mutations vraSR operon have both been implicated development resistance, however molecular mechanisms are not completely understood. To further elucidate leading to transcriptome comparisons were performed using multiple clinical pairs vancomycin-susceptible...
We describe an assay that converts the effects of tRNA-tRNA contacts at two particular codons into a quantitative effect on beta-galactosidase level. The measures separate and combined efficiency suppression adjacent nonsense in vivo using set specially created homologous messages. In survey distal anticodon arm substitutions, we find mutant tRNAs occupying P-site reduce apparent suppressor tRNA reading A-site codon by factors 2-170. By measured distances crystallographic structure, propose...
Human adipose stromal cells (ASCs) reside within the stromal-vascular fraction (SVF) in fat tissue, can be readily isolated, and include stem-like that may useful for therapy. An important consideration clinical application functional studies of stem/progenitor is their capacity to maintain chromosome stability culture. In this study, cultured ASC populations clones were evaluated at intervals maintenance stability. Uncultured SVF (uSVF) included comparison. G-banded analysis demonstrated...
The LRRK2 G2019S mutation is found at higher frequency among Parkinson disease (PD) patients of Ashkenazi Jewish (AJ) ancestry. This study was designed to test whether an internet-based approach could be effective screen and identify carriers. Individuals with without PD AJ ancestry were recruited consented through website. An algorithm applied a series screening questions individuals increased risk carry the mutation. About 1000 completed initial screening. Around 741 qualified for testing...
Mitochondrially mediated apoptosis is characterized by redistribution of proteins from mitochondria to cytoplasm following permeabilization the outer mitochondrial membrane. We applied flow cytometry quantify simultaneously two apoptogenic proteins, cytochrome c (cyt c) and Smac/DIABLO (Smac). Mammalian cells were treated with digitonin that selectively permeabilizes plasma Following fixation, infused successively primary secondary antibodies (the latter fluorescently tagged) enabling...
Thyroid hormones regulate adult metabolism partly through actions on mitochondrial oxidative phosphorylation (OXPHOS). They also affect neurological development of the brain, but their role in cerebral OXPHOS before birth remains largely unknown, despite increase energy demand during neonatal period. Thus, this study examined prepartum hypothyroid fetal sheep. Using respirometry, Complex I (CI), II (CII), and combined CI&CII capacity were measured cerebellum cortex at 128 142 days...
Background Bacteria of the suborder Corynebacterineae include significant human pathogens such as Mycobacterium tuberculosis and M. leprae. Drug resistance in mycobacteria is increasingly common making identification new antimicrobials a priority. Mycobacteria replicate intracellularly, most commonly within phagosomes macrophages, bacterial proteins essential for intracellular survival persistence are particularly attractive targets intervention with generations anti-mycobacterial drugs....
In adults, glucocorticoids act to match the supply and demand for energy during physiological challenges, partly through actions on tissue mitochondrial oxidative phosphorylation (OXPHOS) capacity. However, little is known about role of natural prepartum rise in fetal glucocorticoid concentrations preparing tissues increased postnatal demands. This study examined effect manipulating cortisol sheep late gestation OXPHOS capacity two skeletal muscles with different locomotive functions....
Many cancers preferentially meet their energy requirements through the glycolytic pathway rather than via more efficient oxidative phosphorylation pathway. It is thought that this an important adaptation in cancer malignancy. We investigated whether use of glycolysis for production even presence oxygen (known as Warburg effect) varied between neuroblastoma cell lines with or without MYCN amplification (a key indicator poor disease outcome neuroblastoma).We examined ATP and lactate...
Purpose: Terminally differentiated neurones in the central nervous system need to be protected from stress. We ask here whether differentiation of progenitor cells is accompanied by up-regulation Hsp72, with acquisition enhanced thermotolerance.Materials and methods: Human neuroblastoma SH-SY5Y were propagated an undifferentiated form subsequently into neurone-like cells. Thermotolerance tests carried out exposure various temperatures, monitoring nuclear morphology as index cell death....
The leucine rich repeat kinase 2 (LRRK2) is the most frequently mutated gene in hereditary Parkinson' disease (PD) and all pathogenic LRRK2 mutations result hyperactivation of its function. Here, we describe an easy robust assay to quantify pathway activity human peripheral blood neutrophils by measuring LRRK2-controlled phosphorylation one physiological substrates, Rab10 at threonine 73. immunoblotting analysis described requires a fully selective phosphospecific antibody that recognizes...