Laboratory of Intracellular Signaling in Health and Disease

Functional analysis of immunosuppressive mechanisms of human regulatory B lymphocyte subpopulations in health and various pathologies

Research of functionally relevant non-coding RNAs regulating tumor cell viability and resistance to chemotherapeutic agents in different types of cancer.

The importance of studying SNPs lies in the fact that these genetic variants are often associated with different diseases, as demonstrated by numerous Genome-Wide Association Studies (GWAS). About 95% of clinically significant SNPs are localized in non-coding genomic regions, and their functional significance is likely related to changes in the regulatory characteristics of the regions surrounding the polymorphism. At the genomic level, the mechanism of the functional effect of polymorphisms can involve impaired regulatory element activity due to changes in the DNA sequence at sites for TF-DNA interaction. One example is SNP rs71327024, which is located in the regulatory region of the chemokine receptor gene CXCR6. The minor T-allele of this SNP is associated with severe COVID-19. According to our data, the transcription factor c-Myb binds to the genomic region surrounding the common rs71327024(G) allele, while the risk-associated rs71327024(T) allele, linked to COVID-19 hospitalization, prevents c-Myb binding. This loss of binding leads to a reduction in enhancer properties and a decrease in CXCR6 gene expression.