PROMETHEUS International PhD Student Seminar Series - Jana Zielinski - An Exploration of the Therapeutic Potential of Casein Kinase 1 Delta Inhibition in Breast Cancer Tumorigenesis
| Dates: | 10 July 2023 |
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| Times: | 15:00 - 15:30 |
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| What is it: | Seminar |
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| Organiser: | Faculty of Biology, Medicine and Health |
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| Who is it for: | University staff, Current University students |
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An Exploration of the Therapeutic Potential of Casein Kinase 1 Delta Inhibition in Breast Cancer Tumorigenesis
Jana graduated from the University of Melbourne in 2020 with a Bachelor of Science majoring in Pharmacology. She received her Honours degree in 2021 under the supervision of Prof. Alastair Stewart, with the thesis titled: “The Art and Artefact of Static Culture”, in which she investigated the paradigm of increased pro-inflammatory cytokine expression after treatment with Non-Steroidal Anti-Inflammatory Drugs in static cell culture and the phenomenon of IL-1?-induced epithelial-mesenchymal transition in A549 cells. Jana then began her PhD in 2022 with Prof. Alastair Stewart focusing on the characterisation of Casein Kinase 1 delta in circadian rhythm and breast cancer tumorigenesis.
Casein Kinase 1 Delta (CK1?) is a conserved serine/threonine protein kinase that is highly expressed in metastatic and primary breast tumour cells and involved in diverse cellular growth and survival processes including circadian rhythms and inflammation. When CK1? is knocked down or pharmacologically inhibited, breast tumour cell invasiveness and tumorigenicity is suppressed in cell lines and in orthotopic xenograft mouse models. Recent evidence has strengthened the link between circadian rhythmicity and breast cancer tumorigenesis, as most spontaneous circulating tumour cell intravasation events occurring during sleep. Dual CK1?/? inhibition is therefore a potential anti-cancer therapeutic approach.
There is emerging evidence that pro-inflammatory cytokines promote metastasis. We thus aim to explore the anti-inflammatory effects of a CK1? and CK1? inhibitor, PF670462, in a human breast tumour cell line. Since CK1? is known to regulate the circadian clock by controlling the stability of the clock protein PERIOD2, we have developed a human PER2-firefly luciferase insert for human tumour cell lines in conjunction with a multiplexed body-on-a chip perfusion system to define the influence of CK1? and circadian entrainment on tumorigenesis.
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C?ontact: Jean-Michel.Fustin@Manchester.ac.uk
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Michael Smith Lecture Theatre
Michael Smith Building
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