Research Laboratory «Molecular Immunology»

Scientific results:

The effect of mitochondrial adaptations on the functional properties and polarization of macrophages was established. All tested drugs oligomycin, rotenone, didanosine, antinomycin A, FCCP prevented the polarization of macrophages to pro-oncogenic M2 polarization. It was revealed that induced mitochondrial dysfunction in macrophages prevents pro-oncogenic activation of tumor-associated macrophages during oncogenesis.

M2 polarization macrophages demonstrated increased levels of Raptor/mTOR and LAMP2/mTOR co-localization, which confirms increased mTORC1 activity in M2 macrophages compared to non-activated M0 macrophages.

The role of mitochondrial adaptations in metabolic and functional rearrangements in cancer cells was established. It was found that cells with the highest level of mitochondrial dysfunction were also characterized by the highest proliferation rate. However, we found that the proliferation rate did not correlate with mTORC1 activity in the studied cells.

We profiled colorectal cancer (CRC) cells according to their mitochondrial membrane potential (MMP). We clustered CRC cells into three bioenergetic groups: cells with high OXPHOS levels and relatively low glycolysis (cluster 1); an intermediate phenotype with reduced mitochondrial respiration and increased glycolysis (cluster 2); and a glycolytic phenotype with high glycolysis and minimal mitochondrial respiration (cluster 3). It was found that cells that prefer glycolysis tend to grow and proliferate rapidly. It was found that pharmaceutical compounds aimed at mitochondrial metabolism and homeostasis are more effective in cells with high OXPHOS levels.

It has been discovered that known and clinically approved pharmaceutical compounds that induce mitochondrial dysfunction in tumor-associated macrophages can be used for a new purpose - as potential anti-cancer drugs.

Education and personnel occupational retraining:

2 bachelors, 1 master, 2 highly qualified personnel, 1 candidate of biological sciences have been trained.

6 postgraduate students and 1 doctoral student are in the process of preparing their dissertations.

10 members of the research team have undergone advanced training on the topic of the project.

Cooperation:

• Germany, Neuruppin, Brandenburg Medical School.
• Germany, Marburg, Institute of Systems Immunology, Center for Tumor Biology and Immunology, Philipps University in Marburg.
• Kazakhstan, Astana, Nazarbayev University School of Medicine.