Disputation: Tatjana Bosnjak
Doctoral candidate Tatjana Bosnjak at the Department of Pharmacy, Faculty of Mathematics and Natural Sciences, is defending the thesis "Regulation and functional studies of the cysteine protease legumain in bone cell biology" for the degree of Philosophiae Doctor.
The PhD defence will be fully digital and streamed directly using Zoom. The host of the session will moderate the technicalities while the chair of the defence will moderate the disputation.
Ex auditorio questions: the chair of the defence will invite the audience to ask ex auditorio questions either written or oral. This can be requested by clicking 'Participants -> Raise hand'.
Trial lecture: Lysosomes as intracellular signalling hubs
Main research findings
Legumain is an enzyme present in most cells but its dysregulation is associated with several diseases. During stem cell differentiation, legumain stimulates fat cell and inhibits osteoblast (bone building cells) differentiation. This thesis sheds new light on regulation and function of legumain and explores the possibility of using known drugs to target legumain.
Legumain is normally present in acidic organelles but can also be found outside the cell. This dissertation summarizes extracellular roles of legumain and describes its presence in bone cell exosomes, important for cell-to-cell communication.
Lansoprazole is a commonly used drug against excessive stomach acid production. It was shown that this drug directly inhibits legumain, which could possibly explain osteoporosis as a side effect associated with chronic lansoprazole use.
Vitamin D is important for the development of healthy bones and it was found that this vitamin upregulated legumain activity in the early stages of osteoblast differentiation. Furthermore, this thesis shows that legumain downregulates the expression of vitamin D receptor and enhances expression and degradation of fibronectin. Dysregulation of vitamin D receptor and fibronectin is associated with progression of osteoporosis and other diseases. Therefore, the interplay between vitamin D, fibronectin and legumain takes place at several levels and could be important for bone homeostasis.