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Warsaw University Faculty of Physics
WERSJA POLSKA  Research    People    Education
Name: Dr. hab. Edward Darżynkiewicz (Professor)
Address: Department of Biophysics, Institute of Experimental Physics, Warsaw University, Zwirki i Wigury 93, 02-089 Warsaw, Poland
Phone: +48 22 5540787
E-mail: edek@biogeo.uw.edu.pl
Research interests: Dr. Darżynkiewicz's research concentrates on organic chemistry and biochemistry of nucleic acids. Since middle 80. he has been involved in studying the role of 5' mRNA and 5' U snRNA cap structures in gene expresssion regulation: initiation of protein translation, pre-mRNA splicing and RNA intracellular transport. He has designed and synthesized many model cap analogues which appeared to be invaluable tools for research into molecular mechanisms of the above processes. For example, the synthetic trimethyl guanosine cap anlogues enabled to establish the signalling role of trimethylguanosine cap structure in nuclear import of some of U snRNAs. Both, synthetic cap analogues and affinity resins based on them, helped to isolate and characterize several new regulatory factors, like nuclear cap binding complex (CBC) which is engaged in pre-mRNA splicing, or new cytoplasmic eIF4E isoforms from nematode C.elegans whose functions are under investigation. Selected cap analogs have been used in comprehensive biophysical studies of the molecular recognition of cap structures by specific protein factors. These type of studies are being performed by physicists from Department of Biophysics, who Dr. Darżynkiewicz closely collaborates with (R. Stolarski and J. Antosiewicz). He developed a broad collaboration with biochemical groups from many leading laboratories, like with Dr. R.Rhoads (Louisiana State University in Shreveport, USA), Dr. N.Sonenberg (McGill University in Montreal), Dr. S.Burley (Rockefeller University in New York), Dr. I.Mattaj (EMBL, Heidelberg), Dr. S.Cusack (EMBL, Grenoble).

Since 1990 Dr. Darżynkiewicz's research has been continuously supported by the grants from The Polish Committee for Scientific Research. During 1998-2001 he was a coinvestigator in the Polish-US-Canadian international HFSP grant.

Dr. Darżynkiewicz has authored over 90 original publications and reviews. His publications have been cited over 1000 times in the scientific literature.

Professional experience:
1970 M.Sc. in organic chemistry (Dept. of Chemistry, Warsaw University)
1971 - 1975 Predoctoral Fellow, Department of Chemistry, Warsaw University
1976 1976 Ph.D. in nuclec acids organic chemistry (supervised by Prof. D.Shugar), Dept. Chem., Warsaw University
1976 - 1994 Adjunct (Assistant Professor), Dept. of Biophysics, Inst Exp. Physics, Warsaw University
1978 - 1980 Postdoctoral Fellow (supervised by Dr. Aaron Shatkin), Roche Institute of Molecular Biology, Nutley, NJ, USA
'84, '85,'87 3 x 3 months, Visiting Scientist in the Laboratory headed by Professor Stanley Tahara, University of Southern California, Los Angeles, USA
1988 3 months, Visiting Scientist in Laboratory headed by Professor Harri Lonnberg, University of Turku, turku, Finland
1994 Ph.D. hab. (habilitation) in biochemistry of protein translation, Institute of Biochemistry and Biophysics, Polish Academy of Sciences
1994 - 2001 Dr.hab. (Associate Professor), Dept. of Biophysics, Inst. Exp. Physics, Warsaw University
2001 - Professor, Dept. of Biophysics, Inst. Exp. Physics, Warsaw University
Selected (out of 100) peer-reviewed publications:
  1. Darżynkiewicz E., Stępiński J., Ekiel I., Jin Y., Haber D., Sijuwade T., Tahara S.M., "ß-Globin mRNAs Capped with m7G, m2,7G or m2,2,7G Differ in Intrinsic Translation Efficiency" (1988), Nucleic Acids Res. 16, 8953-8962.
  2. Darżynkiewicz E., Stępiński J., Ekiel I., Goyer C., Sonenberg N., Temeriusz A., Jin Y., Sijuwade T., Haber D., Tahara S.M., "Inhibition of Eukaryotic Translation by Nucleoside 5'-Monophosphate Analogues of mRNA 5'-Cap: Changes in N7 Substituent Affect Analogue Activity" (1989), Biochemistry 28, 4771-4778.
  3. Darżynkiewicz E., Stępiński J., Tahara S. M., Stolarski R., Ekiel I., Haber D., Neuvonen K., Lehikoinen P., Labadi I., Lönnberg H., "Synthesis, Conformation and Hydrolytic Stability of P1, P3-dinucleoside Triphosphates Related to mRNA 5'-Cap, and Comparative Kinetic Studies on Their Nucleoside and Nucleoside Monophosphate Analogs" (1990), Nucleosides & Nucleotides 9, 599-618.
  4. Hamm J., Darżynkiewicz E., Tahara S. M., Mattaj I. W., "The Trimethylguanosine Cap Structure of U1 snRNA Is a Component of a Bipartite Nuclear Targeting Signal" (1990), Cell 62, 569-577.
  5. Fischer U., Darżynkiewicz E., Tahara S. M., Dathan N. A., Lührmann R., Mattaj I. W., "Diversity in the Signals Required for Nuclear Accumulation of U snRNPs and Variety in the Pathways of Nuclear Transport" (1991), J. Cell Biol. 113, 705-714.
  6. Izaurralde E., Stępiński J., Darżynkiewicz E., Mattaj I. W., "A Cap Binding Protein That May Mediate Nuclear Export of RNA Polymerase II-transcribed RNAs" (1992), J. Cell. Biol. 118, 1287-1295.
  7. Izaurralde E., Lewis J., McGuigan C., Jankowska M., Darżynkiewicz E., Mattaj I.W., "A Nuclear Cap Binding Protein Complex Involved in Pre-mRNA Splicing" (1994), Cell. 78, 657-668.
  8. Maroney P.A., Denker J.A., Darżynkiewicz E., Laneve R., Nilsen T.W., "Most mRNA in the Nematode Ascaris lumbricoides Are trans-spliced: A Role for Spliced Leader Addition in Translational Efficiency" (1995), RNA, 1, 714-723.
  9. Joshi B., Cai A-L., Keiper B. D., Minich W. M., 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" (1995), J. Biol. Chem., 270, 14597-14603.
  10. 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 Faktor 4E in Caenorhabditis elegans Can Distinguish between Mono- and Trimethylated mRNA Cap Structures" (1998), J. Biol. Chem. 273, 10538-10542.
  11. 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 Cell-Free Translation" (1999), Biochemistry, 38, 8538-8547.
  12. Lampio A., Ahola T., Darżynkiewicz E., Stępiński J., Jankowska-Anyszka M., Kaariainen L., "Guanosine Nucleotide Analogs as Inhibitors of Alphavirus mRNA Capping Enzyme" (1999), Antivirial Res., 42, 35-46.
  13. 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 (2001) 1486-1495.
  14. NiedĽwiecka A., Marcotrigiano J., Stępiński J., Jankowska-Anyszka M., Wysłouch-Cieszyńska A., Dadlez M., Gingras A-C., Mak P., Darżynkiewicz 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", J. Mol. Biol. 319 (2002) 615-635.
  15. H. Miyoshi, D.S. Dwyer, B. D. Keiper, M. Jankowska-Anyszka, E. Darżynkiewicz, R.E. Rhoads: "Discrimination between mono- and trimethylated cap structures by two isoforms of Caenorhabditis elegans eIF4E", EMBO J. 21 (2002) 4680-4690.
  16. A. Stachelska, Z. Wieczorek, K. Ruszczyńska, R. Stolarski, M. Pietrzak, B. J. Lamphear, R. E. Rhoads, E. Darżynkiewicz, M. Jankowska-Anyszka: "Interaction of three Caenorhabditis elegans isoforms of translation initiation factor eIF4E with mono- and trimethylated mRNA 5' cap analogues", Acta Biochim. Pol. 49 (2002) 671-682.
  17. A. NiedĽwiecka, J. Stępiński, E. Darżynkiewicz, N. Sonenberg, R. Stolarski: "Positive heat capacity change upon specific binding of translation initiation factor eIF4E to mRNA 5' cap", Biochemistry 41 (2002) 12140-12148.
  18. J. Żuberek, A. Wysłouch-Cieszyńska, A. NiedĽwiecka, M. Dadlez, J. Stępiński, W. Augustyniak, A.-Cl. Gingras, Z. Zhang, S. K. Burley, N. Sonenberg, R. Stolarski, E. Darżynkiewicz: "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 (2003) 52-61.
  19. Jemielity J, Fowler T, Żuberek J, Stępiński J, Lewdorowicz M, NiedĽwiecka A, Stolarski R, Darżynkiewicz E, Rhoads RE: Novel 'anti-reverse' cap analogs with superior translational properties. RNA 2003; 9; 1108-1122.
  20. Żuberek J, Jemielity J, Jabłonowska A, Stępiński J, Dadlez M, Stolarski R, Darżynkiewicz E: Influence of electric charge variation at residues 209 and 159 on interaction of eIF4E with the mRNA 5' terminus. Biochemistry 2004; 43; 5370-5379.
  21. Lewdorowicz M, Yoffe Y, Żuberek J, Jemielity J, Stępiński J, Kierzek R, Stolarski R, Shapira M, Darżynkiewicz E: Chemical synthesis and binding activity of the trypanosomatid cap-4 structure. RNA 2004; 10; 1469-1478.
  22. Grudzień E, Stępiński J, Jankowska-Anyszka M, Stolarski R, Darżynkiewicz E. Rhoads RE: Novel cap analogs for in vitro synthesis of mRNAs with high translational efficiency. RNA 2004; 10; 1479-1487.
  23. Cohen LS, Mikhli C, Friedman C, Jankowska-Anyszka M, Stępiński J, Darżynkiewicz E, Davis RE: Nematode m7GpppG - and m32,2,7GpppG - RNA decapping: Activities in Ascaris embryos and characterization of C. elegans scavenger DcpS. RNA 2004; 10; 1609-1624.
  24. Yoffe Y, Żuberek J, Lewdorowicz M, Zeira Z, Keasar C, Orr-Dahan I, Jankowska-Anyszka M, Stępiński J, Darżynkiewicz E, Shapira M: Cap-binding activity of an eIF4E homolog from Leishmania. RNA 2004; 10; 1764-175.
  25. Kałek M, Jemielity J, Stępiński J, Stolarski R, Darżynkiewicz E: A direct method for the synthesis of nucleoside 5'-methylenebis(phosphonate)s from nucleosides. Tetrahedron Lett. 2005; 46; 2417-2421.
  26. Worch R, NiedĽwiecka A, Stępiński J, Mazza C, Jankowska-Anyszka M, Darzynkiewicz E, Cusack S, Stolarski R: Specificity of recognition of mRNA 5' cap by human nuclear cap-binding complex. RNA 2005; 11; 1355-1363.
  27. Westman B, Beeren L, Grudzień E, Stępiński J, Worch R, Żuberek J, Jemielity J, Stolarski R, Darżynkiewicz E, Rhoads RE, Preiss T: The antivirial drug ribavirin does not mimc the 7-methylguanosine moiety of the mRNAs cap structure in vitro. RNA 2005; 11; 1505-1513 .
  28. Grudzien E, Kalek M, Jemielity J, Darzynkiewicz E, Rhoads RE: Differential Inhibition of mRNA Degradation Pathways by Novel Cap Analogs. J. Biol. Chem. 2006; 281; 1857-1867.
  29. Kalek M, Jemielity J, Darzynkiewicz ZM, Bojarska E, Stepinski J, Stolarski R, Davis RE, Darzynkiewicz E: Enzymatically stable 5' mRNA cap analogs: Synthesis and binding studies with human DcpS decapping enzyme. Bioorg. Med. Chem. 2006; 14; 3223-3230.
Participation in research projects:
Role of 5' mRNA and 5' U snRNA cap structures in regulation of gene expression

Studies of the macromolecular structure, dynamics and function in solution

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

Structure and function of cap-4 in early eukaryotes - trypanosomatides; its chemical analogues as potential drug targets against Leishmania