We are happy to report that the ICCVS PhD student Sara Mikac has been awarded a PhD degree. The public defense took place on  4 Nov 2022 at the Intercollegiate Faculty of Biotechnology  of University of Gdansk and Medical University of Gdansk.  Sara successfully defended her thesis on “Identification of a novel, transcription-independent role of Nrf2 in lung cells”. 

The transcription factor Nrf2 is recognized for its pro-survival and cell-protective role upon exposure to different types of extrinsic and intrinsic insults. It controls a number of cellular processes such as proliferation, differentiation, apoptosis, autophagy, protein homeostasis and amino acids metabolism. Under no-stress conditions, the level of Nrf2 is low since it is constantly degraded by Keap1-Cul3-E3 ubiquitin ligase pathway. However, when the regulation of Nrf2 is imbalanced (e.g. via oncogene activation or mutations), it becomes constitutively active promoting carcinogenesis, metastasis and radio- and chemoresistance. Transient activation of Nrf2 in normal cells is protective, however, constitutive activation as seen in cancer, enhances the survival and progression of cancer cells.  

Since oncogenic and immune pathways are interconnected, my PhD project investigated the impact of Nrf2 on the expression of major histocompatibility complex class I (MHC-I) molecules, which present self and non-self peptides to the immune cells. In the course of the project, we have also identified the stable, non-canonically regulated Nrf2 which does not play a transcription factor role. Altogether, these results point to the new function of Nrf2 in cells, which relies on the protein-protein interaction – explains Sara Mikac. 

Research was done at ICCVS under the supervision of Prof. Robin Fahraeus and Dr Alicja Sznarkowska and reviewed by Prof. Albena Dinkova-Kostova, University of Dundee; Prof. dr hab. Alicja Józkowicz, Uniwersytet Jagielloński; and Dr Neda Slade, Institut Ruđer Bošković. 

Congratulations, Sara! 

More information on the thesis: https://bip.ug.edu.pl/st-tyt_nauk/106883/sara_mikac