Digital Public Defence: Paula Lindner
MSc Paula Maria Lindner at Centre for Molecular Medicine Norway will be defending the thesis “Role of endoplasmic reticulum Ca2+ depletion, the unfolded protein response, and autophagy in thapsigargin-induced cell death” for the degree of PhD (Philosophiae Doctor).
The public defence will be held as a video conference over Zoom.
The defence will follow regular procedure as far as possible, hence it will be open to the public and the audience can ask ex auditorio questions when invited to do so.
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Digital Trial Lecture – time and place
See Digital Trial Lecture.
- First opponent: Associate Professor Kasper Rouschop, Faculty of Health, Medicine and Life Sciences, Maastricht University, The Netherlands
- Second opponent: Associate Professor Ernst-Martin Füchtbauer, Department of Molecular Biology and Genetics, Aarhus University, Denmark
- Third member and chair of the evaluation committee: Professor Marit Inngjerdingen, University of Oslo
Chair of the Defence
Professor Tore Jahnsen, University of Oslo
Senior Researcher Nikolai Engedal, Oslo University Hospital
Professor Poul Nissen, Aarhus University
Naturally occurring plant compounds have long tradition in medical research. One of them is thapsigargin, a specific inhibitor of the endoplasmic reticulum (ER) Ca2+ pump SERCA. Thapsigargin has gained attention in cancer treatment because it disturbs intracellular Ca2+ homeostasis, which in turn affects essential cellular processes and eventually drives the cancer cells toward cell death.
This thesis focused on understanding how SERCA inhibition by thapsigargin modulates ER calcium depletion, ER stress signaling, autophagy, and cell death, revealing several novel connections and mechanisms that were previously unrecognized. Cellular methods included knockdowns of specific proteins involved in the ER stress response and autophagy to decipher their contribution to thapsigargin-induced cell death. In addition, monitoring the relation of ER Ca2+ depletion and downstream cellular effects revealed surprisingly strong tolerance of the cells towards ER Ca2+ depletion. Thapsigargin has been used as mother compound for prodrugs designed for cancer therapy. The prodrugs are targeted to the tumor site as an effect of cleavage by cancer-specific proteases, which releases active thapsigargin analogs within the tumor environment. Several such prodrug-derived thapsigargin analogs were included in this study, and effects on SERCA inhibition, ER Ca2+ depletion, stress signaling, and cell death were compared. The new research findings contribute to the understanding of how thapsigargin exerts cytotoxic effects in cancer cells and aids future therapeutic efforts with thapsigargin-derived prodrugs.
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Published May 25, 2020 11:54 AM
- Last modified June 10, 2020 11:51 AM