Dr Nowis and her team focus their research on the mechanisms regulating protein degradation and the function of endoplasmic reticulum (ER) in tumor cells.
Two major pathways operating in mammalian cells are involved in breaking down of damaged, malfunctioning or unnecessary proteins. These are associated with the function of proteasomes and autophagy machinery. Tumor cells due to their increased metabolism and enormous proliferation rate produce huge amounts of proteins that overload their organelles. If such proteins are not swiftly removed they accumulate and become toxic inducing cell death.
The best known example of protein-secreting tumor is multiple myeloma – a bone marrow malignancy originating from antibody-secreting B cells. Inhibition of protein degradation with the use of the novel class of antitumor agents called proteasome inhibitors significantly improved survival of multiple myelomasuffering patients. Dr Nowis group together with Dr Geatano Vattemi from the University of Verona are carefully investigating the influence of proteasome inhibitors not only on tumor but also on normal cells and tissues. Their aim is to help clinicians to optimize the qualification process for proteasome inhibitors treatment so that the chances of developing unexpected side effects by the patients are minimized.
The group is also interested in the mechanisms regulating ER stress – a phenomenon commonly associated with accumulation of misfolded proteins in the endoplasmic reticulum. They study enzymes regulating intracellular amounts of reactive oxygen species as well as the role of chaperones, which are proteins protecting other molecules from damage. These studies will hopefully identify novel targets for cancer treatment.