Prof. Dr hab. Ryszard Stolarski

Division of Biophysics
Institute of Experimental Physics
University of Warsaw
Zwirki i Wigury 93, 02-089 Warsaw, Poland

Phone: +48 22 5540772

E-mail: stolarsk@biogeo.uw.edu.pl

Research interests

Dynamics and thermodynamics of biomolecules and their specific intermolecular interactions, including proteins, DNA and RNA oligomers, e.g. 5' mRNA cap, as well as nucleosides and nucleotides. Molecular structures and relationship between the physicochemical properties of biomolecules and their biological activity. Methods: molecular spectroscopy (NMR, fluorescence), and molecular dynamics (MD) simulations.
The main achievements:
(a) construction of a dynamical model of intermolecular interactions between mRNA 5'-terminus (cap) and the nuclear cap-binding protein complex (CBC), which take part in various processess of gene expression.
(b) completion of methodology for detailed structure determination of short DNA helices, from NMR data to the final conformation, by means of restrained molecular dynamics with NMR constraints (rMD).
(c) detection of a shift in tautomeric equilibrium of the modified nucleoside, N6-methoxy-adenosine, upon formation of associates with complemetary nucleosides through hydrogen bonds as well as hydrogen exchange within the associates; both phenomena being of great importance for spontaneous and chemically induced mutagenesis;
(d) quantitative determination of the conformation about the glycosidic bond in purine nucleosides and nucleotides, and elucidation of discrepancies in the results derived previously;
(e) further insight into structural requirements of various enzymes of the main metabolic pathways toward nucleoside and nucleotide derivatives of potential antivirus and anticancer properties;

Professional experience

1975 - 1982 Department of Biophysics, Institute of Experimental Physics, Warsaw University, Warsaw, Poland; Research and Teaching Assistant
1983 - 1994 Department of Biophysics, Institute of Experimental Physics, Warsaw University, Warsaw, Poland; Research and Teaching Associate (Lecturer)
1983-1985 fellowship of Alexander von Humboldt Foundation at the Institute of Biophysical Chemistry, J.W.Goethe University, Frankfurt am Main, Germany, directed by Prof. Heinz Ruterjans
1989-1990 post-doctoral fellowship in Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA., U.S.A., research adviser Prof. Thomas L. James
1993 research visit in University of Turku, Turku, Finland
1994 - Head of Department of Biophysics
1997 - Professor of University of Warsaw
2006 - Professor

Selected publications

  1. Modrak-Wojcik A., Gorka M., Niedzwiecka K. Zdanowski K., Zuberek J., Niedzwiecka A., Stolarski R.: Eukaryotic translation initiation is controlled by cooperativity effects within ternary complexes of 4E-BP1, eIF4E, and the mRNA 5' cap, FEBS Letters 587, 3928-3934, 2013.
  2. Liu, W., Jankowska-Anyszka, M., Piecyk, K., Dickson, L., Wallace, A., Niedźwiecka, A., Stępiński, J., Stolarski, R., Darżynkiewicz, E., Kieft, J., R. Zhao, R., Jones, D.N.M., Davis, R.E.: Structural Basis for Nematode eIF4E binding an m2,2,7G-Cap and its implications for translation initiation, Nucleic Acids Research 39, 8820-8832, 2011.
  3. Kiraga-Motoszko, K., Niedzwiecka, A. Modrak-Wojcik, A., Stepinski, J., Darzynkiewicz, E., Stolarski, R.: Thermodynamics of molecular recognition of mRNA 5' cap by yeast eukaryotic initiation factor 4E, Journal of Physical Chemistry B 115, 8746-8754, 2011.
  4. Ruszczynska-Bartnik K, Maciejczyk M, R. Stolarski: Dynamical insight into Caenorhabditis elegans eIF4E recognition specificity for mono- and trimethylated structures of mRNA 5' cap, Journal of Molecular Modeling 17, 727-737, 2011.
  5. Worch R., Jankowska-Anyszka M., Niedzwiecka A., Stepinski J., Mazza C., Darzynkiewicz E., Cusack S., Stolarski R.: Diverse role of three tyrosines in binding of the RNA 5' cap to the human nuclear cap binding complex, Journal of Molecular Biology 385, 618-627, 2009.
  6. Worch, R. Stolarski, R.: Stacking efficiency and flexibility analysis of aromatic amino acids in cap-binding proteins, Proteins: Structure, Function, Bioinformatics 71, 2026-2037, 2008.
  7. Rutkowska-Włodarczyk, I., Stępiński, J., Dadlez, M., Darżynkiewicz, E., Stolarski, R., Niedźwiecka A.: Structural changes of eIF4E upon binding to the mRNA 5'monomethylguanosine and trimethylguanosine cap, Biochemistry 47, 2710-2720, 2008.
  8. Niedzwiecka, A.,Stępiński, J., Antosiewicz, J.M., Darżynkiewicz, E., Stolarski R.: Biophysical approach to studies of cap-eIF4E interaction by synthetic cap analogs, Methods in Enzymology 430, 209-245, 2007.
  9. Grudzień-Nogalska, E., Stępiński, J., Jemielity, J., Żuberek, J.,Stolarski, R., Rhoads, R.E., Darżynkiewicz E.: synthesis of anti-reverse cap analogs (ARCAs) and their applications in mRNA translation and stability, Methods in Enzymology 431, 203-227, 2007.
  10. Kałek, M., Jemielity, J., Darżynkiewicz, Z.M., Bojarska, E., Stępiński, J., Stolarski, R., Davis, R.E., Rhoads, R.E., Darżynkiewicz E.: Enzymatically stable 5' mRNA cap analogs: synthesis and binding studies with human DcpS decapping enzyme, Bioorganic & Medicinal Chemistry 14, 3223-3230, 2006.
  11. Westman, B., Beeren, L., Grudzień, E., Stępiński, J., Worch, R., Żuberek, J., Jemielity, J., Stolarski, R., Darżynkiewicz, E., Rhoads, R.E., Preiss, T.: The antiviral drug ribavirin does not mimic the 7-methylguanine moiety of the mRNA cao structure in vitro, RNA 11, 1505-1513, 2005.
  12. Worch, R., Niedzwiecka, A., Stepinski, J., Mazza, C., Jankowska-Anyszka, M., Darzynkiewicz, E., Cusack, S. and Stolarski, R.: Specificity of recognition of mRNA 5' cap by human nuclear cap-binding complex. RNA 11, 1355-1363, 2005.
  13. Niedzwiecka, A., Darzynkiewicz, E., and Stolarski, R.: Thermodynamics and conformational changes related to binding of eIF4E protein to mRNA 5' cap. Journal of Physics: Condensed Matter 17, S1483-1495, 2005
  14. Niedzwiecka, A., Darzynkiewicz, E., and Stolarski, R.: Thermodynamics of mRNA 5' Cap Binding by Eukaryotic Translation Initiation Factor eIF4E. Biochemistry 43, 13305-13317, 2004.
  15. Grudzien, E., Stepinski, J., Jankowska-Anyszka, M., Stolarski, R., Darzynkiewicz, E., and Rhoads, R.E.: Novel Cap Analogs for in vitro Synthesis of mRNAs with High Translational Efficiency. RNA 10, 1479-1487, 2004
  16. Zuberek, J. Jemielity, J., Jablonowska, A., Stepinski, J., Dadlez, M., Stolarski, R., and Darzynkiewicz, E.: Influence of Electric Charge Variation at Residues 209 and 159 on the Interaction of eIF4E with the mRNA 5' Terminus. Biochemistry 43, 5370-5379, 2004
  17. Lewdorowicz, M., Yoffe, Y., Zuberek, J., Jemielity, J., Stepinski, J., Kierzek, R., Stolarski, R., Shapira, M., and Darzynkiewicz, E.: Chemical Synthesis and binding activity of the trypanosomatid cap-4 structure. RNA 10, 1469-1478, 2004
  18. Stolarski R.: Thermodynamics of Specific protein-RNA interactions. Acta Biochimica Polonica 50, 297-318, 2003
  19. Zuberek, J., Wyslouch-Cieszynska, A., Niedzwiecka, A., Dadlez, M., Stepinski, J., Augustyniak, W., Gingras, A.-C., Zhang, Z., Burley, S.K., Sonenberg, N., Stolarski, R., and Darzynkiewicz E. : Phosphorylation of eIF4E Attenuates Its Interaction with mRNA 5' Cap Analogs by Electrostatic Repulsion: Intein-mediated Protein Ligation Strategy to Obtain Phosphorylated Protein. RNA 9, 52-61, 2003
  20. Jemielity, J.,Fowler, T., Zuberek, Stepinski, J., Lewdorowicz, M., Niedzwiecka, A., Stolarski, R., Darzynkiewicz, E., and Rhoads, R.E. : Novel "Anti-Reverse" Cap Analogs with Superior Translational Properties. RNA 9, 1108-1122, 2003
  21. Ruszczynska, K., Kamienska-Trela, K., Wojcik, J. Stepinski, J., Darzynkiewicz, E., and Stolarski, R.: Charge Distribution in 7-Methylguanine Regarding Cation-pi Interaction with Protein Factor eIF4E. Biophysical Journal 85, 1450-1456, 2003
  22. Niedzwiecka, A., Stepinski, J., Darzynkiewicz, E., Sonenberg, N., and Stolarski, R.: Positive heat capacity change upon specific binding of translation initiation factor eIF4E to mRNA 5' cap. Biochemistry 41 (40):12140-12148, 2002.
  23. Niedzwiecka, A., Marcotrigiano, J., Stepinski, J., Jankowska-Anyszka, M., Wyslouch- Cieszynska, A., Dadlez, M., Gingras, A.-C., Mak, P., Darzynkiewicz, E., Sonenberg, N., Burley, S.K. & Stolarski, R.: Biophysical Studies of eIF4E cap-Binding Protein: Recognition of mRNA 5' cap Structure and Synthetic Fragments of eIF4G and 4E-BP1 Proteins, Journal of Molecular Biology 319, 615-635, 2002
  24. Stępiński, J., Waddell, C., Stolarski, R., Darżynkiewicz, E. & Rhoads, R.E.: Synthesis and Properties of mRNAs Containing the Novel "Anti-Reverse" cap Analogs 7-methyl(3'-O-methyl)GpppG and 7-methyl(3'-deoxy)GpppG, RNA 7, 1486-1495, 2001
  25. Cai, A., Jankowska-Anyszka, M., Centers, A., Chlebicka, L., Stępiński, J., Stolarski, R., Darżynkiewicz, E. & Rhoads, R.E.: Quantitative Assessment of mRNA cap Analogs as Inhibitors of in vitro Translation, Biochemistry 38, 8538-8547, 1999
  26. Jankowska-Anyszka, M., Lamphear, B.J., Aamodt, E.J., Harrington, T., Darżynkiewicz, E., Stolarski, R. & Rhoads, R.E.: Multiple Isoforms of Eukaryotic Protein Synthesis Initiation Factor 4E in Caenorhabditis elegans Can Distinguish between Mono- and Trimethylated mRNA cap Structures, Journal of Biological Chemistry 273, 10538-10542, 1998
  27. Wieczorek, Z., Zdanowski, K., Chlebicka, L., Stępiński, J., Jankowska, M., Kierdaszuk, B., Temeriusz, A., Darżynkiewicz, E. & Stolarski, R., Fluorescence and NMR studies of intramolecular stacking of mRNA cap-analogues, Biochim.Biophys. Acta 1354, 145-152, 1997
  28. Stolarski, R., Sitek, A., Stępiński, J., Jankowska, M., Oksman, P., Temeriusz, A., Darżynkiewicz, E., & Shugar, D., 1H-NMR studies on association of mRNA cap-analogues with tryptophan-containing peptides, Biochim. Biophys. Acta 1293, 97-105, 1996
  29. Joshi, B., Cai, B.D. Keiper, A.-L., Minich, W.B., Mendez, R., Beach, C.M., Stępiński, J., Stolarski, R., Darżynkiewicz, E., Rhoads, R.E.: Phosphorylation of eukaryotic protein synthesis initiation factor 4E at Ser-209, Journal of Biological Chemistry 270, 14597-14603, 1995.
  30. Birnbaum, K.B., Stolarski, R. & Shugar, D., Structure and Conformation of the Cyclic Phosphate of Ganciclovir, a Broad Spectrum Antiviral Agent, Biochim. Bophys. Acta 1200, 55-63, 1994
  31. Stolarski, R., Egan, W. & James, T.L., Solution Structure of the EcoRI DNA Octamer Containing 5-Fluorouracil via Restrained Molecular Dynamics Using Distance and Torsion Angle Constraints Extracted from NMR Spectral Simulations, Biochemistry 31, 7027-7042, 1992
  32. Stolarski, R., Kierdaszuk, B., Hagberg, C.E. & Shugar, D., Mechanism of Hydroxylamine Mutagenesis: Tautomeric Shift and Proton Exchange between the Promutagen N6-Methoxyadenosine and Cytidine, Biochemistry 26: 4332-4337, 1987
  33. Stolarski, R., Buck, F., Fera, B. & Ruterjans, H., One- and Two-Dimensional 1H-NMR Investigations of Two 19-Base-Pair Analogues of the tet Operator, Eur. J. Biochem. 169, 603-609, 1987
  34. Stolarski, R., Hagberg, C.E. & Shugar, D., Studies on the Dynamic Syn-Anti Equilibrium in Purine Nucleosides and Nucleotides with the Aid of 1H and 13C NMR Spectroscopy, Eur. J. Biochem. 138, 187, 192, 1984
  35. Stolarski, R., Pohorille, A., Dudycz, L. & Shugar, D., Comparison of Theoretical and Experimental Approaches to Determination of Conformation of Nucleosides about Glycosidic Bond, Biochim. Biophys. Acta 610, 1-19, 1980

Participation in research projects

Translation initiation and intracellular transport: biophysics of protein and RNA interactions