Anatomy and Neurobiology
GRB, 111 S. Penn St., 307C
Education and Training
I graduated from Moscow University with a M.S. degree in bioorganic chemistry and obtained a Ph.D. degree in biophysics from the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow. I received postdoctoral training in biophysics and protein folding with Wayne Bolen at University of Texas Medical Branch and on prions with Nobel laureate Stanley Prusiner at UCSF. In UTMB, I established a pioneering approach for folding natively unfolded proteins. With Dr. Bolen, we described a new thermodynamic force that contributes to protein folding and stability more than 40 years after Kauzmann introduced four basic thermodynamic forces responsible for protein folding. As a postdoctoral fellow with Stanley Prusiner, I laid the ground work on synthetic prions and showed for the very first time that the transmissible prion disease can be induced in animals using amyloid fibrils prepared in vitro.
1996-1998 Postdoctoral Fellow, University of Texas Medical Branch, Galveston, TX, Supervisor Dr. D.W. Bolen
1999-2001 Postdoctoral Fellow, University of California, San Francisco, CA, Supervisor Dr. S.B. Prusiner
2001-2006 Assistant Professor, Medical Biotechnology Center, University of Maryland Biotechnology Institute, Baltimore, MD, USA
2006-2009 Associate Professor, Medical Biotechnology Center, University of Maryland Biotechnology Institute, Baltimore, MD, USA.
2010-2013 Associate Professor, Center for Biomedical Engineering and Technology and Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA
2013 – present Professor, Center for Biomedical Engineering and Technology and Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA
prions, prion diseases, neurodegenerative diseaes
Katorcha, E., Daus, M.L., Gonzalez-Montalban, N., Makarava, N., Lasch, P., Beekes, M., Baskakov, I.V. Reversible off and on switching of prion infectivity via removing and reinstalling prion sialylation. Sci Rep., v.6, e33119.
Srivastava, S., Makarava, N., Katorcha, E., Savtchenko, R., Brossmer, R., Baskakov, I.V. 2015 Post-conversion sialylation of prions in lymphoid tissues. Proc. Natl. Acad. Sci. USA PLUS, p.E6654-6662
Katorcha, E., Makarava, N., Savtchenko, R., D’Arzo, A., Baskakov, I.V. 2014Sialylation of prion protein controls the rate of prion amplification, the cross-species barrier, the ratio of PrPSc glycoform and prion infectivity. PLoS Pathog., v.10, e1004366
Makarava, N., Kovacs, G.G., Savtchenko, R., Alexeeva, I., Ostapchenko, V., Budka, H., Rohwer, R.G., Baskakov, I.V. 2012, A New Mechanism for Transmissible Prion Diseases. J. Neurosci, v..32, p. 7345-7355.
Makarava, N., Savtchenko, R., Alexeeva, I., Rohwer, R.G., Baskakov, I.V. 2012, Fast and ultrasensitive method for quantitating prion infectivity titre. Nature Commun., v. 3, p.741.
Research in my laboratory focuses on elucidating molecular mechanisms responsible for prion replication and structure of infectious forms of the prion protein. Prion diseases, or transmissible spongiform encephalopathies, are fatal neurodegenerative disorders that can arise spontaneously, be inherited or acquired through transmission. The transmissible agent of prion diseases devoid of nucleic acids, but instead consists of a prion protein in its abnormal, β-sheet rich state (PrPSc), which is capable of replicating itself according to the template-assisted mechanism.
Current studies in our laboratory are focused on the following topics: (I) elucidating the role of sialylation in prion replication and prion diseases; (ii) establishing a relationship between prion structure and infectivity; elucidating molecular and structural requirements essential for the prion protein to acquire infectious conformation; (iii) defining molecular features responsible for prion strain diversity.
In the past few years, our laboratory introduced several innovative approaches and concepts, including a new approach for assessing conformation within individual amyloid fibrils and a novel concept on conformational switching within individual fibrils. Our most recent studies introduced a new hypothesis that transmissible prion diseases can be triggered by structures substantially different from that of authentic PrPSc. This concept has important implications for understanding the genesis of infectious prion structures and the etiology of transmissible prion diseases.
Ongoing studies in our laboratory include biochemical, molecular imaging, structural, cellular, pathological and experimental animal approaches to understand the mechanisms by which prions replicate, to define molecular features responsible for prion infectivity and prion strain diversity. Our laboratory is equipped with Atomic Force Microscope PicoLE combined with the inverted fluorescence microscop, CD spectrophotometer J- 810 (Jacso); FTIR spectrometer Tensor 27 equipped (Bruker); fluorimeter FlouroMax-3 (Jobin Yvon); dynamic light scattering DynaPro-MS/X (Protein Solutions); HPLC system with fluorescence and photodiode detectors (Shimadzu); FPLC system Akta prime (Amersham); fluorescence inverted microscope TE-2000 (Nikon); automated sonicators Misonix S-4000.