Doctoral defence in Biology -  Iwona Teresa Myszor

Live stream: https://livestream.com/hi/doktorsvorniwonamyzsor

Ph.D. student: Iwona Teresa Myszor

Dissertation title: Effects of aroylated phenylenediamines and mechanical stress on lung epithelial immunity

Opponents: 
Dr. Henk P. Haagsman, Professor at the Department Biomolecular Health Sciences, Utrecht University, The Netherlands
Dr. Sif Hansdóttir, MD, Chief Physician of Pulmonary Medicine at Landspitali University Hospital and Adjunct Lecturer at the Faculty of Medicine, University of Iceland

Advisor: Dr.Guðmundur Hrafn Guðmundsson, Professor at the Faculty of Life and Environmental Sciences, University of Iceland

Doctoral committee: 
Dr. Þórarinn Guðjónsson, Professor at the Faculty of Medicine, University of Iceland
Dr. Sigurbergur Kárason, MD, Professor at the Faculty of Medicine, University of Iceland and Chief of Intensive Care, Landspitali University Hospital
Dr. Margrét Helga Ögmundsdóttir, Associate Professor at the Faculty of Medicine, University of Iceland

Chair of Ceremony: Dr. Anna Dóra Sæþórsdóttir, Professor and the Head of the Faculty of Life and Environmental Sciences, University of Iceland

Abstract:
Innate immunity of the lung epithelium provides efficient defenses against pathogens or other stress factors by secretion of antimicrobial peptides, presence of cellular junction proteins and autophagy. Upon activation through epithelial cell receptors the system triggers a defense response. Activation of epithelial immunity can lead to elimination of bacteria, enhanced epithelial integrity and lysosomal degradation. Therefore, modulation of immune signaling for epithelial immunity by specific inducers can serve as a treatment strategy to fight infections. The use of innate immunity modulators is of interest for management of ventilator induced lung injury (VILI), that can lead to acute respiratory distress syndrome (ARDS) in patients.

The aim of this work was to investigate the effect of the aroylated phenylenediamine (APD) inducers HO53 and HO56 and mechanical stress on the innate immunity in the lung epithelium.
The novel compounds HO53 and HO56 induced expression of antimicrobial effectors in bronchial epithelium and reduced bacterial entry. Both APD inducers exhibited a synergistic effect with vitamin D on CAMP gene expression and HO53 activated the STAT3 transcription factor. The HO53 compound enhanced epithelial barrier integrity and promoted induction of autophagy in differentiated cells. Treatment with HO53 had broad effect on gene expression, including expression of histone modifying enzymes and stimulated AMPK pathway together with TFEB activation.
Mechanical stress generated by the cyclical pressure air-liquid device (CPAD) affected cell morphology and expression of markers for VILI and ARDS development together with pro-inflammatory genes. A preliminary study indicates that HO53 compound exacerbates pro-inflammatory response induced by mechanical stress.

About the doctoral candidate
Iwona Teresa Myszor was born in Poland on the 27th of November 1991. She studied at Jagiellonian University in Cracow, where she obtained her Bachelor’s degree in biology in 2013 and Master degree in Biochemistry in 2015. After her studies, she conducted a traineeship through the Erasmus Plus Practice Scheme in Medical Research Council Centre for Molecular Bacteriology and Infection, at Imperial College London. After that, she returned to Poland and in 2016 worked in the Institute of Pharmacology of the Polish Academy of Sciences in Cracow. Iwona started her PhD studies in Biology at the Faculty of Life and Environmental Sciences of the University of Iceland in January 2017 and conducted her research at Biomedical Center.