senior lecturer , vice chair
Telefon: 32496, *0259
Supervisor: FAUST, Zsuzsanna
Co-supervisor: Dr. NAGY, Tamás
It is well known that intracellular signaling mechanisms aprticipating in the malignant transformation of the cell. For example the mutant protein coded by the fusion gen bcr-abl is an activated tyrosin-kinase which results in increased phosphorylation on many signaling protein. Despite the recognition of protein O-Glycosylation as a signaling mechanism is a more recent event, it seems to be more and more obvious that it plays a significant role in the development of malignant diseases. During O-Glycosylation, a single N-acetyl-glucosamine molecule is linked to the Ser/Thr residues of proteins. This process can be reversible, can be competing with phosphorylation for the same Ser/Thr sites and occurs on a large scale of various types of proteins. E.g. the proto-oncogen c-myc or the tumor-supressor p53 can both be O-Glycosylated. Interestingly, the cells’ carbohydrate metabolism is associated (in both direction) with O-Glycosylation. Influencing O-Glycosylation (by specific drugs) can impact the glucose uptake of the cells and could be exploited as therapeutic target in malignant diseases.
In this research, our aim is to study the level of protein O-Glycosylation in various malignant hematologic diseases. Characterizing O-GlcNAc levels could be a useful diagnostic marker, but also the basis for developing new therapies.
Supervisor: NAGY, Tamás
Co-supervisor: Prof. Dr. MISETA, Attila
The 2 main molecular hallmarks of Alzheimer’s disease are the senile plaques (β-amyloid peptides) and neuro-fibrillary tangles (hyperphosphorylated tau proteins). Several studies demonstrated that chronic hypoglycemia that occurs more frequently in elderly people might be an significant cause of the disease. Due to lower glucose levels in the neurons, several post-translational modification requiring carbohydrates might change. E.g. O-Glycosylation, which competes for the same sites on protein with phosphorylation will be down-regulated, thus enabling tau proteins to be hyperphosphorylated. The ER stress and the so called “unfolded protein response” (UPR) is also associated with Alzheimer’s, which might be the consequence of aberrant N-glycans on both β-amyloid and tau.
The aim of the study is to better identify the various protein post-translational modifications that are altered due to hypoglycemia. Moreover, it is necessary to explore the impact of these changes on cellular functions such as viability, morphology, proliferation, etc. Lastly, the long term aim of the study is to find diagnostic markers that predict the development of Alzheimer’s at an early stage.
Supervisor: MISETA, Attila
Co-supervisor: Dr. NAGY, Tamás
The occurrence of bipolar disorder is about 1.2% for both sexes worldwide. Lithium is a frequently employed mood-stabilizer eventhough the exact molecular mechanism of its action is not known. One of its effects is replacing magnesium on proteins, including the enzyme called phosphoglucomutase (PGM). PGM, which is a key enzyme in galactose and glycogen metabolism, catalyses the reversible conversion of glucose-1-P (Glc-1-P) to glucose-6-P (Glc-6-P).
Interestingly, alterations in PGM activity also impact intracellular calcium regulation. We have shown earlier in a S. cerevisiae model that inhibiting PGM by lithium increased intracellular calcium storage, but decreased the calcium signals in excited cells. In the present study we will investigate the link between metabolic changes (PGM inhibition) and calcium regulation. According to our hypothesis and our preliminary results, the role of endoplasmic reticulum and protein post-translational modifications are key elements in this process.