Yuri Lyubchenko, Ph.D., Dr.Sc.


Department of Pharmaceutical Sciences
College of Pharmacy
University of Nebraska Medical Center
986025 Nebraska Medical Center
Omaha, NE 68198-6025
402-559-1971 (Office)
402-559-1973 (Lab)
402-559-9543 (Fax)

Teaching Activities:
In the graduate program, Dr. Lyubchenko teaches in PHSC-845: Quantitative Pharmaceutical Sciences, PHSC-921/BIOC-921: Biophysical Chemistry, Biochemistry 850: Laboratory Techniques in Biochemistry and Molecular Biology.  He also coordinates a recent course in Bioimaging and Nanoimaging focused on applications of nanotechnology to pharmaceutical science and biomedicine.

Research Activities/Interests:
Nanoscale Structure, Dynamics and Interactions - Seeing and Manipulating Biomolecules.

Dr. Lyubchenko’s research plans fall generally into three large areas:

  • Structural Genomics - DNA Structure, Dynamics and Function;
  • Molecular mechanisms Alzheimer's, Parkinson's and similar protein misfolding diseases
  • Nanoimaging - Nanotechnology Applications for Medicine

The structural genomics projects are centered around chromatin structure and dynamics and DNA recombination and replication.  In the chromatin area, we utilized time-lapse AFM to investigate the spontaneous unwrapping of nucleosomes and have proposed a novel model of chromatin dynamics.  The recent experiments with the use of a revolutionary high-speed AFM are capable of imaging the dynamics of molecules with video rate, and these have yielded new insights into the pathways of chromatin dynamics.  The availability of new AFM methodology is critical for understanding mechanisms of site-specific DNA recombination.

Misfolding and aggregation of proteins are widespread phenomena leading to the development of numerous neurodegenerative disorders such as Parkinson’s, Alzheimer’s, and Huntington’s diseases and there is no cure for any of these devastating protein misfolding diseases. Misfolded states of proteins exist intermittently, so elucidating the mechanism of the formation and the protein aggregation requires the use of methods capable of probing transient conformations of proteins. We developed a novel approach in which misfolded states are probed with AFM force spectroscopy.  Using this approach, we were able to identify misfolded states of the protein and characterize their properties.  The major finding is that a misfolding dimer has an extremely long lifetime in comparison with the fast conformational dynamics of monomers usually occurring on the microsecond-nanosecond time scale.  The high stability of misfolded dimers is a fundamental finding, suggesting that the formation of dimers leads to enormous stabilization of the protein misfolded state.  Future studies will provide us with critical information needed for the development of novel and efficient prevention tools, diagnostics and therapeutics for the protein misfolding diseases.

Development of novel nanotechnology for various biomedical applications is an ultimate goal of the research projects under the Nanoimaging program.  We developed an entirely novel surface chemistry enabling us to develop one of the most versatile methodologies for AFM imaging.  A spin-off from our research has been improvements in the AFM force spectroscopy methodology.  There are now rapidly developing and exciting applications of AFM in molecular pharmacology, drug design and other biomedical applications.  AFM is capable of direct imaging of molecular dynamics and interactions and we are working on technology development facilitating these studies.  Animated images below illustrate the power of this approach for direct imaging of such process as branch migration of Holliday junction (paper 5 in the list below) and unwrapping process of nucleosomes (paper 9 in the list below).

Movie 1– Holliday junction branch migration; paper 6, see more movies on the journal site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12949070

Movie 2 – Spontaneous unwrapping of nucleosomes; paper 9; see more movies on the journal site:

Director of Nanoimaging Core facility.

For more information, please visit the Nanoimaging Core Facility website.
Selected Publications:

  1. Lushnikov, A.Y.; Bogdanov, A.; Lyubchenko, Y.L.; DNA Recombination: Holliday Junctions Dynamics and Branch Migration. J Biol Chem. Vol. 278, no. 44, pp. 43130-43134, 2003.
  2. Lyubchenko, Y.L.; DNA Structure and Dynamics: An Atomic Force Microscopy Study. Cell Biochem Biophys vol. 41, no. 1, pp. 75-98, 2004.
  3. Lyubchenko, Y.L.; Sherman, S.; Shlyakhtenko, L.S.; Uversky, V.N.; Nanoimaging For Protein Misfolding and Related Diseases. J Cell Biochem, vol. 99, no. 1, pp. 52-70, 2006.
  4. Shlyakhtenko, L.S.; Lushnikov, A.Y.; Lyubchenko, Y.L.; Dynamics of Nucleosomes Revealed By Time-Lapse Atomic Force Microscopy. Biochemistry, vol. 48, no. 33, pp. 7842-7848, 2009.
  5. Lyubchenko, Y.L.; Shlyakhtenko, L.S.; AFM For Analysis of Structure and Dynamics of DNA and Protein-DNA Complexes. Methods, vol. 47, no.3, pp. 206-213, 2009.
  6. Krasnoslobodtsev, A.V.; Portillo, A.M.; Decker-Gaudig, T.; Deckert, V.; Lyubchenko, Y.L.; Nanoimaging for Prion related Diseases. Prion, vol. 4, no.4, pp. 265-274, 2010.
  7. Lyubchenko, Y.L.; Kim, B.H.; Krasnoslobodtsev, A.V.; Yu, J.; Nanoimaging for Protein Misfolding Diseases. Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology. vol. 2, no. 5, pp. 526-543, 2010.
  8. Lyubchenko, Y.L.; Shlyakhtenko, L.S.; Ando, T.; Imaging of Nucleic Acids With Atomic Force Microscopy. Methods, [epub ahead of print], 2011.
  9. Yu, J.; Warnke, J.; Lyubchenko, Y.L.; Nanoprobing of Alpha-Synuclein Misfolding and Aggregation with Atomic Force Microscopy. Nanomedicine: Nanotechnology, Biology, and Medicine, vol. 7, no.2, pp. 146-152, 2011.
  10. Shlyakhtenko, L.S.; et al. Atomic Force Microscopy Studies Provide Direct Evidence for Dimerization of the HIV Restriction Factor APOBEC3G. The Journal of Biological Chemistry. vol. 286, no. 5, pp. 3387-3395, 2011.

For a complete list of Dr. Lyubchenko's references, please click here.

Yuri Lyubchenko, Ph.D.
Dr. Lyubchenko