Studies of selenoprotein functions in health and disease

Cellular reduction and oxidation (redox) processes are crucial determinants for physiological as well as pathological processes. Selenoproteins play particularly important roles in this context.

Focusing on this topic, we aim to address the following specific questions:- How do the activities of the main cytosolic or mitochondrial thioredoxin (Trx)-fold proteins that are substrates of selenoprotein thioredoxin reductases (TrxRs) compare when assessed side-by-side, with regards to activities with key substrates such as peroxiredoxins, ribonucleotide reductase, nitrosylated proteins, persulfidated proteins, disulfides and cystine?- What specific roles do the selenoproteins thioredoxin reductase 1 (TrxR1, also named TXNRD1) and glutathione peroxidases 1 and 4 (GPX1 and GPX4) play in cancer, and how can drug targeting of these selenoproteins be utilized for development of new and more efficient anticancer therapy protocols?- How do redox modulated transcription factors underpin the anticancer effects of selenoprotein targeting, including altered activities of Nrf2, NFkB, HIF, STAT3 and p53?- By what mechanisms may thioredoxin interacting protein (TXNIP) interact with the functions of Nrf2 and thereby regulate metabolic aberrations in diabetes and in cancer cells?- Can secreted proteins from the thioredoxin (Trx) and glutathione (GSH) systems that increase in serum during disease provide new reliable biomarkers for the assessment of cancer progression and therapeutic responses?