Irina Bezsonova, PhD

Ubiquitination and Cancer: The p53 signaling pathway is a complex multi-component network central to cancer biology. Over 50% of all tumors have mutated tumor suppressor p53. The primary focus of my reasearch is structural and biochemical characterization of proteins and protein complexes of p53 pathway, especially, proteins responsible for maintenance of an appropriate level of p53 in the cell such as E3 ubiquitin ligase Hdm2 and ubiquitin-specific protease USP7. We use structural biology tools, NMR spectroscopy and X-ray crystallography, in conjunction with other biophysical and biochemical methods to determine 3D structures of proteins and characterize their interactions with specific binding partners. Detailed knowledge of protein structure provides the basis for rational design of new drugs suitable for anti-cancer therapies. Ubiquitination and Epigenetics: Epigenetic marks work as molecular switches that regulate expression of our genes without altering the DNA sequence itself. It is through epigenetic marks that environmental factors like diet, stress and prenatal nutrition can make an imprint on genes that is passed from one generation to the next. These marks include modifications of histone tails (methylation, acetylation, phosphorylation, ubiquitination, etc) and DNA methylation. Ubiquitination of residue K119 of the histone H2A, for example, is a hallmark of stably repressed developmental genes in stem cells and inactive X-chromosome. We study Polycomb Repressive Complexes PRC1 and PRC2 responsible for developmental gene suppression and maintenance of "stemness" of a cell. PRC2 and PRC1 are multi-protein enzymatic complexes that methylate histone H3 and ubiquitinate histone H2A resulting in stable gene silencing. We are interested in structural organization of these complexes and molecular mechanism of gene recognition and gene silencing by these multi-subunit repressors.

[2026 Mar] High-pH NMR to Identify Macromolecular Hydrogen-Bonds and Foldons. [2026 Feb] Human DNA polymerase η is regulated by mutually exclusive mono-ubiquitination and mono-NEDDylation. [2025 Oct] Small-molecule allosteric activator of ubiquitin-specific protease 7 (USP7). [2025 Sep] Functional spectrum of USP7 pathogenic variants in Hao-Fountain syndrome: Insights into the enzyme's activity, stability, and allosteric modulation. [2025 Sep] The C-terminal Tail of Ubiquitin-Specific Protease 7 Facilitates Ubiquitin Release and Ensures Efficient Catalytic Turnover. [2025 Jul] Divide-and-conquer strategy for NMR studies of the E. coli γ-clamp loader complex. [2025 May] Activation dynamics of ubiquitin-specific protease 7. [2024 Dec] Differences in structure, dynamics and Zn-coordination be