Recent Developments in the Patho-Physiological Molecular Clocks Lab
When it is dark enough, you can see the mice!
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Led by Smith and driven by Lauren Garbutt at Warwick and US collaborators in the labs of Prof Weaver at UMass Med School as well as Prof Harrington at Smith College and Prof Davidson at Morehouse, the first Preprint about the novel tissue-specific Dbp reporter mice, and only 8 years after its inception. |
Endocrine Related Cancers review on what stop tumours ticking, how to determine it, and why it might be important
In a great joint effort by ARAP student Ewan Stephenson and MRC DTP student Laura Usselmann with Ewan's Singaporean co-supervisors David Virshup (DUKE-NUS) and Vinay Tergongar (A*STAR), we are providing an in depth look into clocks in tumours.
2-year post-doctoral position to work on tumour clocks
This position is associated with a three years CRUK funded Multidisciplinary Award jointly lead by Dr Robert Dallmann (WMS) and Professor David A. Rand (Maths) to determine if the circadian clock in cancer cells holds potential to predict cancer patient survival. The Research Fellow will be based in Biomedical Sciences Division of WMS and work in the new Inter-disciplinary Biomedical Research Building at the Gibbet Hill Campus Site of University of Warwick. However, you will also work in close collaboration with the project team of Mathematicians, Statisticians and Bioinformaticians.
Please do get in touch if you are interested and have further questions.
Email: r.dallmann (at) warwick.ac.uk
Did we wake up in time for better stroke treatment translation?
In a commentary led Warwick colleague Johannes Boltze and Nadine Diwischus and Munich researchers Martha Merrow and Nikolaus Plesnia in the Journal of Cerebral Blood Flow and Metabolism, we argue that recent discoveries on the considerable circadian modulation of treatment in stroke might explain some of translational failures in therapeutic development in this area.
FY26 a new Osmium complex to treat cancer
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Led by Swati Kumar and in collaboration with the Sadler, Perrier and Lévi groups, we investigated the chronotherapy with novel organo-osmium complex [OsII(ɳ6-p-cym)(PhAzPy-NMe2)I]+ (FY26), and show that 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. |
