Publications
A complete up-to-date list of publications of Robert can be found on Google Scholar and full-texts might be available from the Warwick Research Active Portal (WRAP).
Cancer clocks in tumourigenesis: the p53 pathway and beyond
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Circadian rhythms regulate a vast array of physiological and cellular processes, as well as the hormonal milieu, to keep our cells synchronised to the light-dark cycle. Epidemiologic studies have implicated circadian disruption in the development of breast and other cancers, and numerous clock genes are dysregulated in human tumours. Here we review the evidence that circadian rhythms, when altered at the molecular level, influence cancer growth. We also note some common pitfalls in circadian-cancer research and how they might be avoided to maximise comparable results and minimise misleading data. Studies of circadian gene mutant mice, and human cancer models in vitro and in vivo, demonstrate that clock genes can impact tumourigenesis. Clock genes influence important cancer related pathways, ranging from p53-mediated apoptosis to cell cycle progression. Confusingly, clock dysfunction can be both pro- or anti- tumourigenic in a model and cell type specific manner. Due to this duality, there is no canonical mechanism for clock interaction with tumourigenic pathways. To understand the role of the circadian clock in patients’ tumours requires analysis of the molecular clock status compared to healthy tissue. Novel mathematical approaches are under development, but this remains largely aspirational, and is hampered by a lack of temporal information in publicly available datasets. Current evidence broadly supports the notion that the circadian clock is important for cancer biology. More work is necessary to develop an overarching model of this connection. Future studies would do well to analyse the clock network in addition to alterations in single clock genes. |
Circadian effects on stroke outcome – Did we not wake up in time for neuroprotection?
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The occurrence of stroke in humans peaks in the morning. A recent study revealed that time of day mitigates the therapeutic impact of neuroprotective paradigms. These findings might not only explain the previous failure of trans- lation of neuroprotective therapies but inspire new paradigms in stroke chronopathophysiology research. Taking chro- notype into account may complement the many factors that influence efficacy of experimental therapies in stroke. |
Dose and time-dependent tolerability and efficacy of organo-osmium complex FY26 and its tissue pharmacokinetics in hepatocarcinoma-bearing mice
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The organo-osmium complex [OsII(ɳ6-p-cym)(PhAzPy-NMe2)I]+ (FY26) exhibits promising in vitro antitumour activity against mouse hepatocarcinoma Hepa1-6 and other mouse or human cancer cell lines. Here, we drastically enhance water solubility of FY26 through the replacement of the PF6-counter-anion with chloride using a novel synthesis method. FY26.PF6 and FY26.Cl displayed similar in vitro cytoxicity in two cancer cell models. We then show the moderate and late anticancer efficacy of FY26.PF6 and FY26.Cl in a subcutaneous murine hepatocarcinoma mouse model. Both efficacy and tolerability varied according to FY26 circadian dosing time in hepatocarcinoma tumour-bearing mice. Tumour and liver uptake of the drug were determined over 48 h following FY26.Cl administration at Zeitgeber 6 (ZT6), when the drug is least toxic (in the middle of the light span when mice are resting). Our studies suggest the need to administer protracted low doses of FY26 at ZT6 in order to optimize its delivery schedule, for example through the use of chrono-releasing nanoparticles. |
Low-Cost Microfabrication Tool Box
Microsystems are key enabling technologies, with applications found in almost every industrial field, including in vitro diagnostic, energy harvesting, automotive, telecommunication, drug screening. Yet, their development for commercial or educational purposes has typically been limited to specialized laboratories in upper-income countries. In this paper, we describe a range of low-cost approaches and equipment (below £1000), which will enable researchers to build a low-cost toolbox.
Review on how stress increases the susceptibility to herpes simplex virus type 1 primary and recurrent infections
Following primary infection, HSV-1 establishes latency and reactivates under stress. Stress disturbs inner immune Yin–Yang balance, increasing the susceptibility to HSV-1 infection. In latent infection, stress induces changes in hormone level, chromosomal modification and oxidation, thereby disturbing the Yin–Yang balance between HSV-1 and the host defense, leading to recurrent diseases.