Recent Developments in the Patho-Physiological Molecular Clocks Lab
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. |
Preprint on microfluidics on the cheap
The Charmet lab and friends have put together a tool-kit for microfabrication on a budget with contributions from Ben. Now available as a preprint.
New research article in Scientific Reports on circadian Pgp expression and its importance for drug transporters
Co-lead author Swati A. Kumar in a collaboration with Annabelle Ballesta, Alper Okyar, Francis Lévi, Enza Piccolo and us entitled: Sex-, feeding-, and circadian time-dependency of P-glycoprotein expression and activity - implications for mechanistic pharmacokinetics modeling, we described how time-of-day of drug adminstration might lead to different pharmacokinetic profiles in male and female mice.
Alper Okyar, Swati Kumar, Elisabeth Filipski, Enza Piccolo, Narin Ozturk, Helena Xandri-Monje, Zeliha Pala, Kristin Abraham, Ana Rita Gato de Jesus Gomes, Mehmet N. Orman, Xiao-Mei Li, Robert Dallmann, Francis Lévi, Annabelle Ballesta, Scientific Reports, 2019, DOI: 10.1038/s41598-019-46977-0
Denise Vlachou's TimeTeller is out!
If you want to know what circadian phase a tissue has, but your patient is only willing to get biopsied once and not 6 times in 24 hours: Use TimeTeller
New paper on circadian dynamics of mitochondria and energy metabolism
Cellular ATP levels are modulated by the circadian clock influencing mitochondrial network dynamics through DRP1 phosphorylation.