All Outputs (20)

Precision Medicine and the Role of Biomarkers of Radiotherapy Response in Breast Cancer (2020)
Journal Article
Meehan, J., Gray, M., Martínez-Pérez, C., Kay, C., Pang, L. Y., Fraser, J. A., …Turnbull, A. K. (2020). Precision Medicine and the Role of Biomarkers of Radiotherapy Response in Breast Cancer. Frontiers in Oncology, 10, https://doi.org/10.3389/fonc.2020.00628

Radiotherapy remains an important treatment modality in nearly two thirds of all cancers, including the primary curative or palliative treatment of breast cancer. Unfortunately, largely due to tumor heterogeneity, tumor radiotherapy response rates ca... Read More about Precision Medicine and the Role of Biomarkers of Radiotherapy Response in Breast Cancer.

hASH1 nuclear localization persists in neuroendocrine transdifferentiated prostate cancer cells, even upon reintroduction of androgen (2019)
Journal Article
Fraser, J. A., Sutton, J. E., Tazayoni, S., Bruce, I., & Poole, A. V. (2019). hASH1 nuclear localization persists in neuroendocrine transdifferentiated prostate cancer cells, even upon reintroduction of androgen. Scientific Reports, 9, Article 19076 (2019). https://doi.org/10.1038/s41598-019-55665-y

Neuroendocrine prostate cancer (NEPC) is thought to arise as prostate adenocarcinoma cells transdifferentiate into neuroendocrine (NE) cells to escape potent anti-androgen therapies however, the exact molecular events accompanying NE transdifferentia... Read More about hASH1 nuclear localization persists in neuroendocrine transdifferentiated prostate cancer cells, even upon reintroduction of androgen.

Silver nanoparticles promote the emergence of heterogeneic human neutrophil sub-populations (2018)
Journal Article
Kemp, S., Young, L., Ross, M., Prach, M., Hutchison, G. R., Malone, E., & Fraser, J. A. (2018). Silver nanoparticles promote the emergence of heterogeneic human neutrophil sub-populations. Scientific Reports, 8(1), Article 7506. https://doi.org/10.1038/s41598-018-25854-2

Neutrophil surveillance is central to nanoparticle clearance. Silver nanoparticles (AgNP) have numerous uses, however conflicting evidence exists as to their impact on neutrophils and whether they trigger damaging inflammation. Neutrophil’s importanc... Read More about Silver nanoparticles promote the emergence of heterogeneic human neutrophil sub-populations.

Preferential activation of HIF-2α adaptive signalling in neuronal-like cells in response to acute hypoxia (2017)
Journal Article
Martín-Aragón Baudel, M. A. S., Rae, M. T., Darlison, M. G., Poole, A. V., & Fraser, J. A. (2017). Preferential activation of HIF-2α adaptive signalling in neuronal-like cells in response to acute hypoxia. PLOS ONE, 12(10), Article e0185664. https://doi.org/10.1371/journal.pone.0185664

Stroke causes severe neuronal damage as disrupted cerebral blood flow starves neurons of oxygen and glucose. The hypoxia inducible factors (HIF-1α and HIF-2α) orchestrate oxygen homeostasis and regulate specific aspects of hypoxic adaptation. Here we... Read More about Preferential activation of HIF-2α adaptive signalling in neuronal-like cells in response to acute hypoxia.

Preferential activation of HIF-2 adaptive mechanisms in neuronal-like cells in response to hypoxia (2017)
Presentation / Conference
Fraser, J., Baudel, M., Rae, M., Darlison, M., & Poole, A. (2017, April). Preferential activation of HIF-2 adaptive mechanisms in neuronal-like cells in response to hypoxia. Poster presented at British Neuroscience Association - festival of neuroscience 2017

Stroke is a leading cause of death and disability worldwide. Blockage, or occlusion, of cerebral arteries causes irreversible neuronal damage as disrupted blood flow starves neurones of oxygen and glucose. The hypoxia inducible factors (HIFs) are mas... Read More about Preferential activation of HIF-2 adaptive mechanisms in neuronal-like cells in response to hypoxia.

The expression of the chloride co-transporters NKCC1 and KCC2 is reversed in the penumbra following (2017)
Conference Proceeding
Baudel, M., Rae, M., Fraser, J., & Poole, A. (2017). The expression of the chloride co-transporters NKCC1 and KCC2 is reversed in the penumbra following. In Brain and Neuroscience: BNA 2017 Festival of Neuroscience: Abstract Book

Stroke is one of the major causes of death and disability worldwide. The harm caused by the interruption of blood flow to the brain unfolds in the subsequent hours and days, so it is critical to identify new therapeutic targets that could reduce neur... Read More about The expression of the chloride co-transporters NKCC1 and KCC2 is reversed in the penumbra following.

Investigating the molecular mechanisms driving neuroendocrine differentiation in androgen deprived prostate cancer cells (2016)
Conference Proceeding
Sutton, J., Hutchison, G., Fraser, J., & Poole, A. (2016). Investigating the molecular mechanisms driving neuroendocrine differentiation in androgen deprived prostate cancer cells

Background: Neuroendocrine differentiation is commonplace in prostate tumors treated with androgen deprivation therapy and is associated with castrate-resistant disease progression and poor prognosis. The molecular mechanisms driving neuroendocrine d... Read More about Investigating the molecular mechanisms driving neuroendocrine differentiation in androgen deprived prostate cancer cells.

Phosphomimetic Mutation of the N-Terminal Lid of MDM2 Enhances the Polyubiquitination of p53 through Stimulation of E2-Ubiquitin Thioester Hydrolysis (2014)
Journal Article
Fraser, J. A., Worrall, E. G., Lin, Y., Landre, V., Pettersson, S., Blackburn, E., …Hupp, T. R. (2015). Phosphomimetic Mutation of the N-Terminal Lid of MDM2 Enhances the Polyubiquitination of p53 through Stimulation of E2-Ubiquitin Thioester Hydrolysis. Journal of Molecular Biology, 427(8), 1728-1747. https://doi.org/10.1016/j.jmb.2014.12.011

Mouse double minute 2 (MDM2) has a phosphorylation site within a lid motif at Ser17 whose phosphomimetic mutation to Asp17 stimulates MDM2-mediated polyubiquitination of p53. MDM2 lid deletion, but not Asp17 mutation, induced a blue shift in the λm... Read More about Phosphomimetic Mutation of the N-Terminal Lid of MDM2 Enhances the Polyubiquitination of p53 through Stimulation of E2-Ubiquitin Thioester Hydrolysis.

Imaging of activated complement using ultrasmall superparamagnetic iron oxide particles (USPIO) - conjugated vectors: an in vivo in utero non-invasive method to predict placental insufficiency and abnormal fetal brain development (2014)
Journal Article
Girardi, G., Fraser, J., Lennen, R., Vontell, R., Jansen, M., & Hutchison, G. (2015). Imaging of activated complement using ultrasmall superparamagnetic iron oxide particles (USPIO) - conjugated vectors: an in vivo in utero non-invasive method to predict placental insufficiency and abnormal fetal brain development. Molecular Psychiatry, 20(8), 1017-1026. https://doi.org/10.1038/mp.2014.110

In the current study, we have developed a magnetic resonance imaging-based method for non-invasive detection of complement activation in placenta and foetal brain in vivo in utero. Using this method, we found that anti-complement C3-targeted ultras... Read More about Imaging of activated complement using ultrasmall superparamagnetic iron oxide particles (USPIO) - conjugated vectors: an in vivo in utero non-invasive method to predict placental insufficiency and abnormal fetal brain development.

In vivo in uterus non-invasive methods to predict placental insufficiency and adverse pregnancy outcomes in antiphospholipid syndrome (2014)
Conference Proceeding
Girardi, G., Fraser, J., Bertolaccini, M. L., Lennen, R., Vontell, R., & Hutchison, G. (2014). In vivo in uterus non-invasive methods to predict placental insufficiency and adverse pregnancy outcomes in antiphospholipid syndrome. https://doi.org/10.1016/j.placenta.2014.06.184

Objectives: To use MRI-based methods to non invasively detect placental insufficiency and predict fetal outcomes in obstetric antiphospholipid syndrome (APS) Methods and result: A) Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles conjug... Read More about In vivo in uterus non-invasive methods to predict placental insufficiency and adverse pregnancy outcomes in antiphospholipid syndrome.

Nanoparticles and Neutrophil Activation (2012)
Presentation / Conference
Dickson, C., Prach, M., Fraser, J., Ingram, L., Barlow, P., Hutchison, G., …Malone, E. (2012, February). Nanoparticles and Neutrophil Activation. Presented at NanoImpactNet-QNANO conference - European Network on the Health and Environmental Impact of Nanomaterials, Dublin, Ireland

Neutrophils, the rapid responders of the innate immune system, are central to the initial immune responses of a host to foreign particles. Circulating in the blood, they are the predominant leukocyte (40-75%), and are positioned to rapidly migrate to... Read More about Nanoparticles and Neutrophil Activation.

A Novel p53 Phosphorylation Site within the MDM2 Ubiquitination Signal: II. A MODEL IN WHICH PHOSPHORYLATION AT SER269 INDUCES A MUTANT CONFORMATION TO p53. (2010)
Journal Article
Fraser, J. A., Madhumalar, A., Blackburn, E., Bramham, J., Walkinshaw, M. D., Verma, C., & Hupp, T. R. (2010). A Novel p53 Phosphorylation Site within the MDM2 Ubiquitination Signal: II. A MODEL IN WHICH PHOSPHORYLATION AT SER269 INDUCES A MUTANT CONFORMATION TO p53. Journal of Biological Chemistry, 285, 37773-37786. https://doi.org/10.1074/jbc.M110.143107

The p53 DNA-binding domain harbors a conformationally flexible multiprotein binding site that regulates p53 ubiquitination. A novel phosphorylation site exists within this region at Ser269, whose phosphomimetic mutation inactivates p53. The phosphomi... Read More about A Novel p53 Phosphorylation Site within the MDM2 Ubiquitination Signal: II. A MODEL IN WHICH PHOSPHORYLATION AT SER269 INDUCES A MUTANT CONFORMATION TO p53..

A Novel p53 Phosphorylation Site within the MDM2 Ubiquitination Signal: I. PHOSPHORYLATION AT SER269 IN VIVO IS LINKED TO INACTIVATION OF p53 FUNCTION. (2010)
Journal Article
Fraser, J. A., Vojtesek, B., & Hupp, T. R. (2010). A Novel p53 Phosphorylation Site within the MDM2 Ubiquitination Signal: I. PHOSPHORYLATION AT SER269 IN VIVO IS LINKED TO INACTIVATION OF p53 FUNCTION. Journal of Biological Chemistry, 285, 37762-37772. https://doi.org/10.1074/jbc.M110.143099

p53 is a thermodynamically unstable protein containing a conformationally flexible multiprotein docking site within the DNA-binding domain. A combinatorial peptide chip used to identify the novel kinase consensus site RXSΦ(K/D) led to the discovery o... Read More about A Novel p53 Phosphorylation Site within the MDM2 Ubiquitination Signal: I. PHOSPHORYLATION AT SER269 IN VIVO IS LINKED TO INACTIVATION OF p53 FUNCTION..

Regulation and Function of the Original p53- Inducible p21 Gene (2010)
Book Chapter
Fraser, J. A. (2010). Regulation and Function of the Original p53- Inducible p21 Gene. In p53; Molecular Biology Intelligence Unit, 100-116. Springer Science + Business Media. https://doi.org/10.1007/978-1-4419-8231-5_7

P21 is a well known regulator of cell cycle progression through its inhibitory actions on Cyclin dependent kinases, (Cdk)/cyclin complexes, and DNA replication via its binding to proliferating cell nuclear antigen (PCNA). p21 also has a role in many... Read More about Regulation and Function of the Original p53- Inducible p21 Gene.

A Central Role for CK1 in Catalyzing Phosphorylation of the p53 Transactivation Domain at Serine 20 after HHV-6B Viral Infection (2008)
Journal Article
MacLaine, N. J., Øster, B., Bundgaard, B., Fraser, J. A., Buckner, C., Lazo, P. A., …Hupp, T. R. (2008). A Central Role for CK1 in Catalyzing Phosphorylation of the p53 Transactivation Domain at Serine 20 after HHV-6B Viral Infection. Journal of Biological Chemistry, 283, 28563-28573. https://doi.org/10.1074/jbc.M804433200

The tumor suppressor protein p53 is activated by distinct cellular stresses including radiation, hypoxia, type I interferon, and DNA/RNA virus infection. The transactivation domain of p53 contains a phosphorylation site at Ser20 whose modification st... Read More about A Central Role for CK1 in Catalyzing Phosphorylation of the p53 Transactivation Domain at Serine 20 after HHV-6B Viral Infection.

The MDM2 Ubiquitination Signal in the DNA-Binding Domain of p53 Forms a Docking Site for Calcium Calmodulin Kinase Superfamily Members (2007)
Journal Article
Craig, A. L., Chrystal, J. A., Fraser, J. A., Sphyris, N., Lin, Y., Harrison, B. J., …Hupp, T. R. (2007). The MDM2 Ubiquitination Signal in the DNA-Binding Domain of p53 Forms a Docking Site for Calcium Calmodulin Kinase Superfamily Members. Molecular and Cellular Biology, 27(9), 3542-3555. https://doi.org/10.1128/mcb.01595-06

Genetic and biochemical studies have shown that Ser20 phosphorylation in the transactivation domain of p53 mediates p300-catalyzed DNA-dependent p53 acetylation and B-cell tumor suppression. However, the protein kinases that mediate this modification... Read More about The MDM2 Ubiquitination Signal in the DNA-Binding Domain of p53 Forms a Docking Site for Calcium Calmodulin Kinase Superfamily Members.

Chemical Genetics Approach to Identify Peptide Ligands that Selectively Stimulate DAPK-1 Kinase Activity (2007)
Journal Article
Fraser, J. A., & Hupp, T. R. (2007). Chemical Genetics Approach to Identify Peptide Ligands that Selectively Stimulate DAPK-1 Kinase Activity. Biochemistry, 46(10), 2655-2673. https://doi.org/10.1021/bi061562j

Dissection of signal transduction pathways has been advanced by classic genetic approaches including targeted gene deletion and siRNA-based inhibition of gene product synthesis. Chemical genetics is a biochemical approach to develop small peptide-mim... Read More about Chemical Genetics Approach to Identify Peptide Ligands that Selectively Stimulate DAPK-1 Kinase Activity.

Antioxidant and cytoprotective responses to redox stress (2004)
Journal Article
Mathers, J., Fraser, J. A., McMahon, M., Saunders, R. D. C., Hayes, J. D., & McLellan, L. I. (2004). Antioxidant and cytoprotective responses to redox stress. Biochemical Society symposia, 71, 157-176. https://doi.org/10.1042/bss0710157

Aerobic cells produce reactive oxygen species as a consequence of normal cellular metabolism, and an array of antioxidant systems are in place to maintain the redox balance. When the redox equilibrium of the cell is upset by pro-oxidant environmental... Read More about Antioxidant and cytoprotective responses to redox stress.

The Modifier Subunit of Drosophila Glutamate-Cysteine Ligase Regulates Catalytic Activity by Covalent and Noncovalent Interactions and Influences Glutathione Homeostasis in Vivo (2003)
Journal Article
Fraser, J. A., Kansagra, P., Kotecki, C., Saunders, R. D. C., & McLellan, L. I. (2003). The Modifier Subunit of Drosophila Glutamate-Cysteine Ligase Regulates Catalytic Activity by Covalent and Noncovalent Interactions and Influences Glutathione Homeostasis in Vivo. Journal of Biological Chemistry, 278(47), 46369-46377. https://doi.org/10.1074/jbc.m308035200

Glutamate-cysteine ligase (GCL) has a key influence on glutathione homeostasis. It has been proposed that mammalian GCL is regulated by the redox environment, and we show here that cysteine residues in the Drosophila melanogaster GCL modifier subunit... Read More about The Modifier Subunit of Drosophila Glutamate-Cysteine Ligase Regulates Catalytic Activity by Covalent and Noncovalent Interactions and Influences Glutathione Homeostasis in Vivo.

Drosophila melanogasterGlutamate-Cysteine Ligase Activity Is Regulated by a Modifier Subunit with a Mechanism of Action Similar to That of the Mammalian Form (2001)
Journal Article
Fraser, J. A., Saunders, R. D. C., & McLellan, L. I. (2002). Drosophila melanogasterGlutamate-Cysteine Ligase Activity Is Regulated by a Modifier Subunit with a Mechanism of Action Similar to That of the Mammalian Form. Journal of Biological Chemistry, 277(2), 1158-1165. https://doi.org/10.1074/jbc.m106683200

Glutamate-cysteine ligase (GCL) plays an important role in regulating glutathione homeostasis. In mammals, it comprises a catalytic (GCLC) and modifier (GCLM) subunit. The existence of a modifier subunit in invertebrates has not been described to dat... Read More about Drosophila melanogasterGlutamate-Cysteine Ligase Activity Is Regulated by a Modifier Subunit with a Mechanism of Action Similar to That of the Mammalian Form.