Prof Gyorgy Szabadkai

Research summary

The overarching aim of my research group is to understand how transcriptional and translational regulation of the mitochondrial proteome (termed as mitochondrial biogenesis) is converted into bioenergetic and signaling responses of the organelle. In particular, we focus on how coordinated regulation of mitochondrial biogenesis provides adaptation to mitochondrial stress in primary and secondary mitochondrial disease. We aim to use unbiased approaches to identify components of adaptive mitochondrial biogenesis pathways which will represent therapeutic targets to develop novel treatment strategies.

Ongoing projects in my laboratory have characterised a series of adaptive mechanisms covering the function of the PGC-1 family of transcriptional co-regulators and the neuroprotective redox chaperone DJ-1 under protein unfolding and genotoxic stress conditions. In addition, we have developed novel computational approaches to analyse exome sequencing, transcriptome and proteome data focusing on genes covering the mitochondrial proteome. Using these approaches we identified novel transcriptional networks regulating mitochondrial biogenesis in response to cellular stress accompanying major pathologies, such as neurodegenerative disease, cardiomyopathies and cancer. Finally, we demonstrated the pathological role of mitochondrial Ca2+ overload in human disease. Accordingly, we have developed, validated and applied screening strategies to identify chemical compounds targeting mitochondrial Ca2+ signalling pathways to prevent Ca2+ mediated pathologies.    

Publications

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