Recent Developments in the Patho-Physiological Molecular Clocks Lab
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
|
|
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. |
Covid Chocolate Calendar Alert
As 2020 is drawing to a close we take comfort in some well dosed daily chocolate. Advent calendars as standard issue for all doctoral students in the lab.
Looking for an opportunity to write an application for a 2-year EU funded ISF-EUTOPIA post-doctoral fellowship (MSCF)?
If you are interested in working with us in collaboration with Damiana Rozman at the University of Ljubljana in Slovenia and us in Warwick.
We are looking for candidates of any nationality that have not lived in the UK (or alternatively, not in the Slovenia) for the past 3 years (MSCF mobility rules apply) with a PhD in biosciences. Experience in 3D cell culture and an interest in circadian clocks and cancer would be a great asset.
Please do get in touch ASAP!
BSN project award for Lauren to further characterise a novel tissue-specific bioluminescence reporter model
We are thankful to the British Society for Neuroendocrinology for supporting Lauren's work to characterise a novel circadian reporter model and develop new strategies for recording tissue level bioluminescence data from freely behaving animals.