Dmitry M. Korzhnev, Ph.D.Associate Professor, Department of Molecular Biology and Biophysics
|M.S.||Moscow Institute of Physics and Technology||Applied Physics and Mathematics|
|Ph.D.||Moscow Institute of Physics and Technology||Biophysics|
|Postdoctoral||Swedish NMR Centre at Göteborg University||Post-Doctoral Fellow in Structural Biology in Swedish NMR Centre at Göteborg University under supervision of Prof. M. Billeter|
|Postdoctoral||Shemyakin-Ovchinnikov Inst. Bioorganic Chemistry||Research training in Structural Biology under supervision of Prof. A.S. Arseniev|
|Postdoctoral||University of Toronto||Post-Doctoral Fellow in Structural Biology (NMR) under supervision of Prof. L.E. Kay|
The primary focus of my laboratory is studies of protein structure, dynamics and interactions using structural biology methods, including nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography. We make use of cutting-edge TROSY-NMR techniques that allow to access structural dynamics and interactions of protein assemblies with molecular weights of up to 1 MDa, opening an avenue for deciphering molecular mechanisms of their action.
The underlying cause of cancer is spontaneous mutations introduced to genomic DNA. Reactive products of cellular metabolism and external genotoxic agents cause persistent DNA damage, which is constantly removed through various DNA repair mechanisms. It is unavoidable, however, that some DNA modifications (lesions) persist into S-phase, creating blocks for progression of the DNA replication machinery. To circumvent this problem organisms in all kingdoms of life have evolved DNA damage tolerance pathways, employing specialized enzymes that bypass DNA lesions while temporarily leaving DNA damage unrepaired. The vast majority of mutations are introduced in the genome by enzymes of error-prone branch of DNA damage tolerance - translesion DNA synthesis (TLS). Genetic changes that ensue as a result of TLS are at the root of the onset of cancer and the development of various resistance mechanisms displayed by relapsed tumors, which represents a major problem for treatment of some types of cancer, including ovarian and lung. Our research is aimed at obtaining a detailed atomic-resolution picture of structure, dynamics and interactions of proteins and protein assemblies involved in DNA damage tolerance pathways that will aid the development of new strategies for cancer therapy.
Intermediate and transition states of biomolecular processes represent a paradigm of functionally important structure in biology. For example, protein self-assembly involves the formation of partially folded and misfolded protein states prone to aggregation implicated in a number of human disorders, including type-II diabetes, Alzheimer's and Parkinson's diseases. Although the characterization of such species can provide vital clues about the mechanisms of the underlying processes, it is extremely challenging to examine such states because they are populated at low levels and are not readily isolated. One of the research directions in my laboratory is studies of intermediate and transition states of protein folding and binding using novel NMR relaxation dispersion methodology.
Accepting Lab Rotation Students: Summer 2021, Fall 2021, and Spring 2022
Lab Rotation Projects
- Structure, dynamics and interactions of proteins involved in DNA damage tolerance pathways
- Studying folding mechanisms of single-domain proteins. Structure determination of folding intermediates