PD Dr. Roman Fedorov participates in RESIST research projects D4.

My Research Interest in RESIST

The innate immune sensors activate interferon-driven antiviral responses upon recognition of pathogen-associated molecular patterns and serve as a rheostat for the metabolic activity of the microbiota and its exposure to diet, xenobiotics, and infections. The ability to modulate innate immune sensors opens new ways to novel antiviral and anti-inflammatory drugs and therapies against cancer and many aging-associated metabolic, neoplastic, autoimmune, or autoinflammatory disorders. Using unbiased experimental screening combined with computer-aided rational drug design approaches, we aim at developing small-molecule allosteric effectors that specifically enhance or reduce the enzymatic activity of members of the family of innate immune sensors, such as cyclic GMP-AMP synthases (cGAS) and 2′-5′ oligoadenylate synthetases (OAS). To study structural states and conformational changes associated with substrate binding and product release mechanisms of innate immune sensors cGAS and OAS, we apply a combination of three advanced cutting-edge methodologies: time-resolved serial femtosecond crystallography, on-chip substrate or product binding studies, and high-pressure crystallography. The obtained mechanistic information will be used to develop specific allosteric activity modulators of innate immune sensors.

Contact

PD Dr. Fedorov about his scientific work

PD Dr. Roman Fedorov – Curriculum Vitae

Current Position

  • Since 2004 Head of the research group “Macromolecular Mechanisms” Institute for Biophysical Chemistry, MHH

Undergraduate and Postgraduate Training

  • 1987 – 1992 Study of Chemistry, Krasnoyarsk State University, and Moscow State University, The Soviet Union / Russian Federation (Master of Science in Chemistry).

  • 1992 – 1995 Ph.D. program in Physical and Quantum Chemistry, Moscow State University, Russian Federation

  • 1996 – 2000 Ph.D. program in Structural and Molecular Biology, Institute of Protein Research, Russian Academy of Sciences, Pushchino, Moscow Region, Russian Federation

  • 2001 Ph.D. degree in Chemistry, M.V. Lomonosov Moscow State University, Russian Federation

  • 2016 Habilitation in Biophysical Chemistry, “Enzymatic Activity and Allosteric Regulation,” Hannover Medical School, Germany

Academic and Research Posts

  • 1998 Visiting scientist. Institute for Protein Research, Osaka University, Osaka, Japan

  • 1998 – 1999 Visiting scientist. Department of Molecular Biophysics, Lund University, Lund, Sweden

  • 2000 Researcher. Group of Structural Studies of Ribosomal Proteins, Institute of Protein Research, Russian Academy of Sciences, Pushchino, Moscow Region, Russian Federation

  • 2001 – 2003 Postdoctoral fellow. Department of Physical Biochemistry, Max-Planck-Institute for Molecular Physiology, Dortmund, Germany

  • 2003 Postdoctoral fellow. Department of Biomolecular Mechanisms, Max-Planck Institute for Medical Research, Heidelberg, Germany

  • Since 2004 Group Leader, Institute for Biophysical Chemistry & Research Division for Structural Biochemistry, Hannover Medical School, Germany

Other Scientific Roles

  • Since 2020 Spokesman of Structural Biology division of German Crystallographic Society (DGK)

  • 2017 – 2019 Vice Spokesman of Structural Biology division of German Crystallographic Society (DGK)

  • Since 2006 Responsible for the Life Sciences Block Allocation Group for synchrotron research at the European Synchrotron Radiation Facility

Awards and Prizes

  • 2002 – 2003 Alexander von Humboldt Foundation research fellowship for highly qualified scholars and scientists

  • 2000 Russian Biochemical Society Award for Young Outstanding Scientists

  • 1995 – 1996 George Soros International Science Foundation

Recommended Links

For further information about PD Dr. Fedorov’s scientific work please check the following links:

10 Selected Publications

Prakash O, Führing J, Post J, Shepherd SM, Eadsforth TC, Gray D, Fedorov R and Routier FH. Identification of Leishmania major UDP-Sugar Pyrophosphorylase Inhibitors Using Biosensor-Based Small Molecule Fragment Library Screening. (2019) Molecules, 24(5): 996. DOI:10.3390/molecules24050996

Cramer JT, Führing JI, Baruch P, Brütting C, Knölker H-J, Gerardy-Schahn R, and Fedorov R. Decoding Allosteric Networks in Biocatalysts: Rational Approach to Therapies and Biotechnologies. (2018) ACS Catalysis. 8:2683-2692. DOI: 10.1021/acscatal.7b03714

Hirschmann F, Krause F, Baruch P, Chizhov I, Mueller JW, Manstein DJ, Papenbrock J,  Fedorov R. Structural and biochemical studies of sulphotransferase 18 from Arabidopsis thaliana explain its substrate specificity and reaction mechanism. (2017) Sci. Rep. 7(1):4160.

Lohöfener J, Steinke N, Kay-Fedorov P, Baruch P, Nikulin A, Tishchenko S, Manstein DJ, and Fedorov R. The activation mechanism of 2’-5’-oligoadenylate synthetase gives new insights into OAS/cGAS triggers of innate immunity. (2015) Structure. 23(5):851-862. DOI: 10.1016/j.str.2015.03.012.

Führing JI, Cramer JT, Schneider J, Baruch P, Gerardy-Schahn R, and Fedorov R. A Quaternary Mechanism Enables the Complex Biological Functions of Octameric Human UDP-glucose Pyrophosphorylase, a Key Enzyme in Cell Metabolism. (2015) Sci. Rep. 5, 9618; DOI:10.1038/srep09618.

Führing J, Cramer JT, Routier FH, Lamerz A-C, Baruch P, Gerardy-Schahn R and Fedorov R. Catalytic mechanism and allosteric regulation of UDP-glucose pyrophosphorylase from Leishmania major. (2013) ACS Catalysis. 3:2976-2985.

Hellert J, Weidner-Glunde M, Krausze J, Richter U, Adler H, Fedorov R, Pietrek M, Rückert J,  Ritter C, Schulz TF, Lührs T. A Structural Basis for BRD2/4-Mediated Host Chromatin Interaction and Oligomer Assembly of Kaposi Sarcoma-Associated Herpesvirus and Murine Gammaherpesvirus LANA Proteins. (2013) PLoS Pathog 9(10): e1003640. doi:10.1371/journal.ppat.1003640

Fedorov R, Böhl M, Tsiavaliaris G, Hartmann FK, Taft MH, Baruch P, Brenner B, Martin R, Knölker H-J, Gutzeit HO & Manstein DJ. The mechanism of pentabromopseudilin inhibition of myosin motor activity. (2009) Nature Structural & Molecular Biology, 16, 80-88.

Fedorov R, Witte G, Urbanke C, Manstein DJ, Curth U. 3D structure of Thermus aquaticus single-stranded DNA-binding protein gives insight into the functioning of SSB proteins. (2006) Nucleic Acids Res 34, 6708-6717.

Fedorov R, Vasan R, Ghosh DK and Ilme Schlichting. Structures of nitric oxide synthase isoforms complexed with the inhibitor AR-R17477 suggest a rational basis for specificity and inhibitor design. (2004) PNAS  101, 5892-5897.

Contact

  PD Dr. Roman Fedorov
  Macromolecular Mechanisms, Hannover Medical School (MHH)
  Institute for Biophysical Chemistry, Hannover Medical School (MHH)
Carl-Neuberg-Straße 1
30625 Hannover
  +49 511 532 3705
  Roman.Fedorov
@mh-hannover.de