Dr hab. Jacek Jemielity, Prof. UW

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

Phone: +48 22 5540774 lub +48 22 5540788
E-mail: jacekj@biogeo.uw.edu.pl
Research group website: www.jemielitygroup.pl

Research interests

Synthesis of nucleotides and their analogs important biologically and therapeutically. Synthesis of oligophosphates bearing various modifications (phosphorothioate, phosphoroselenoate, boranophosphate, bisphosphonate, imidodiphosphate, dichloro- and difluorobisphosphaonates). Synthesis of 5' mRNA end analogs (cap analogs) and their applications in the process of gene expression (initiation of translation, mRNA degradation). Therapeutic applications of modified nucleotides and RNA. Synthesis of labeled nucleotides (e.g. fluorescently, isotopically, biotinylated) and their use in the studies of biological processes and role of macromolecules in cell.

Education and professional experience

June 1997 M.Sc. - in Organic Chemistry, Faculty of Chemistry, University of Warsaw, Poland
January 2002 Ph.D. - in Organic Chemistry, Faculty of Chemistry, University of Warsaw, Poland
July 2002 Institute of Structural Biology, Grenoble, France (1 month). Inhibiton of protein biosynthesis with synthetic mRNA cap analogues
Feb. - Sept. 2002 Assistant - Department of Biophysics, Institute of Experimental Physics, University of Warsaw, Poland
June - August 2003 University of Turku, Turku, Finland (3 months). Solid phase synthesis of capped oligonucleotides (mRNA cap analogues)
October 2002 Adjunct - Department of Biophysics, Institute of Experimental Physics, University of Warsaw, Poland
October 2012 Habilitation (Faculty of Chemistry, University of Warsaw, Poland)

Patents

  1. Jemielity J., Grudzien-Nogalska E., Kowalska J., Darzynkiewicz E., Rhoads R.E "Synthesis and use of anti-reverse phosphorothioate analogs of the messenger RNA cap" US Patent 8, 153, 773, April 10 2012

Patent Applications

  1. Jemielity J., Grudzien-Nogalska E., Kowalska J., Darzynkiewicz E., Rhoads R.E "Synthesis and use of anti-reverse phosphorothioate analogs of the messenger RNA cap" United States Provisional Application No. 60/944,842, 19 June 2007, converted on 19 June 2008 into non-provisional USA and PCT Application No. PCT/US2008/67494
  2. Jemielity J., Grudzien-Nogalska E., Kowalska J., Darzynkiewicz E., Rhoads R.E. "Cząsteczka RNA oraz sposób otrzymywania peptydów lub białka", Polish Patent Application, 19 June 2007, No. P 382703
  3. Kowalska J. Jemielity J., Darżynkiewicz E., Łukaszewicz M., Żuberek J. "Nowe boranofosforanowe analogi dinukleozydów, ich zastosowanie, cząsteczka RNA, sposób otrzymywania RNA, oraz otrzymywania peptydów lub białka." Polish Patent Application, 6 June 2008, No. P 385388
  4. Kowalska J. Jemielity J., Darżynkiewicz E., Rhoads R.E., Lukaszewicz M., Zuberek J. "mRNA Cap Analogs". PCT Patent Application, 4 June 2009, No. PCT/US2009/046249
  5. Sahin, U., Kuhn A.N., Darzynkiewicz E., Jemielity, J., Kowalska, J., "Vaccine composition comprising 5'-cap modified RNA" PCT/EP2010/004760 (03.08.2010)

Awards

  1. University of Warsaw Rector's award (2nd degree) for scientific achievements - 2011
  2. Rector Grzegorz Białkowski Award from Faculty of Physics, University of Warsaw (shared with dr Joanna Żuberek, mgr Joanna Kowalska) for "Designing and chemical synthesis of mRNA cap analogues and biophysical studies of their interaction with protein factors" - December 2008
  3. Stipend of The Polityka Foundation "Zostańcie z nami" VIII edition - October 2008
  4. University of Warsaw Rector's award (3rd degree) for scientific achievements - 2004
  5. Scientific stipend of The Rector of The University of Warsaw in years 2004, 2005, 2006, 2007

Participation in research projects

  1. Biotinilated and fluorescence labeled analogs of mRNA 5' end (cap) - new possibilities in examinations of the function of cap structure and mRNA metabolism; MNiSW Nr N N204 089438, (2010-2013), PI: dr hab. Jacek Jemielity
  2. Multifunctional role of mRNA 5' end (cap): from biology to therapy. MNiSW własny nr N N301 096339 (2010 -2013) PI: Prof. dr hab. Edward Darzynkiewicz
  3. Optimization of oligonucleotide nano-therapeutics by stabilization of a structure of signal of nuclear import - trimethyl-cap. 02/EuroNanoMed/2011, NCBiR, ERA-NET EuroNanoMed, (2010 - 2013), PI: Prof. dr hab. Edward Darżynkiewicz
  4. Conjugates of analogs of mRNA 5' end with nanomaterials and biomolecules of a potential application in pharmacology or diagnostics. UMO-2011/01/D/ST5/05869 (13.12.2011- 12.12.2016) PI: dr Joanna Kowalska
  5. Chemical synthesis and estimation of biological properties of analogs of 5'-diphosphate 7-methylguanosine as inhibitors of decapping enzymes. UMO-2011/01/N/NZ1/04326 (12.12.2011-11.12.2014), PI: mgr Marcin Ziemniak

Selected publications (1998-2013)

2013

  1. Dabrowski-Tumanski P., Kowalska J., Jemielity J. Efficient and rapid synthesis of nucleoside diphosphate sugars from nucleoside phosphorimidazolides, Eur J Org Chem (2013) in press.
  2. Grudzien-Nogalska E., Kowalska J., Wei Su, Andreas N. Kuhn, Sergey V. Slepenkov, Edward Darzynkiewicz, Ugur Sahin, Jacek Jemielity, Robert E. Rhoads , Synthetic mRNAs with Superior Translation and Stability Properties, Methods in Molecular Biology 969, 55-72 (2013).
  3. Su W., Slepenkov S.V., Slevin M.K., Lyons S.M., Ziemniak M., Kowalska J., Darzynkiewicz E., Jemielity J., Marzluff W.F., Rhoads R.E. mRNAs containing the histone 3' stem-loop are degraded primarily by decapping mediated by oligouridylation of the 3' end, RNA 19, 1-16 (2013).

    2012
  4. Jemielity J., Lukaszewicz M., Kowalska J., Czarnecki J., Zuberek J., Darzynkiewicz E., Synthesis of biotin labelled cap analogue - incorporable into mRNA transcripts and promoting cap-dependent translation. Organic& Biomolecular Chemistry 10, 8570-8574 (2012) - inside cover picture.
  5. Strenkowska M., Wanat P., Ziemniak M., Jemielity J., Kowalska J., Preparation of Synthetically Challenging Nucleotides Using Cyanoethyl P-Imidazolides and Microwaves. Organic Letters 14, 4782-4785 (2012).
  6. Kowalska J., Osowniak A., Zuberek J., Jemielity J., Synthesis of nucleoside phosphosulfates. Bioorganic & Medicinal Chemistry Letters 22, 3661-3664 (2012).
  7. Szczepaniak S.A., Zuberek J., Darzynkiewicz E., Kufel J., Jemielity J., Affinity resins containing enzymatically resistant mRNA cap analogs-a new tool for the analysis of cap-binding proteins. RNA 18, 1421-1432 (2012).
  8. Rydzik, A. M., Kulis, M., Lukaszewicz, M., Kowalska, J. , Zuberek, J., Darzynkiewicz, Z. M., Darzynkiewicz, E., Jemielity, J., Synthesis and properties of mRNA cap analogs containing imidodiphosphate moiety - fairly mimicking natural cap structure, yet resistant to enzymatic hydrolysis. Bioorganic and Medicinal Chemistry 20, 1699-1710 (2012) - cover picture
  9. Wypijewska A., Bojarska E., Lukaszewicz M., Stepinski J., Jemielity J.,. Davis R.E, Darzynkiewicz E., 7-methylguanosine diphosphate (m7GDP) is not hydrolyzed but strongly bound by decapping scavenger (DcpS) enzymes and potently inhibits their activity. Biochemistry 51, 8003-8013 (2012)

    2011
  10. Su, W., Slepenkov, S., Grudzien-Nogalska, E., Kowalska, J., Kulis, M., Zuberek, J., Lukaszewicz, M., Darzynkiewicz, E., Jemielity, J., Rhoads, R.E. Translation, stability, and resistance to decapping of mRNAs containing caps substituted in the triphosphate chain with BH(3), Se, and NH. RNA 17, 978-988 (2011).
  11. Frank F., Fabian M.R., Stepinski J., Jemielity, J., Darzynkiewicz, E., Sonenberg, N., Nagar B., Structural analysis of 5 '-mRNA-cap interactions with the human AGO2 MID domain. EMBO Reports 12, 415-420 (2011).
  12. Guranowski A.,Wojdyla A.M., Rydzik A.M. , Stepinski J., Jemielity J., Plant nucleoside 5 '-phosphoramidate hydrolase; simple purification from yellow lupin (Lupinus luteus) seeds and properties of homogeneous enzyme. Acta Biochimica Polonica 58, 131-136 (2011).

    2010
  13. Kuhn A.N., Diken M., Kreiter S., Selmi A., Kowalska, J. Jemielity, J., Darzynkiewicz, E., Huber, C., Tureci O., Sahin, U. Phosphorothioate cap analogs increase stability and translational efficiency of RNA vaccines in immature dendritic cells and induce superior immune responses in vivo. Gene Therapy 17, 961-971 (2010).
  14. Jemielity, J. Kowalska, J., Rydzik, A. M., Darzynkiewicz, E., Synthetic mRNA cap analogs with modified triphosphate bridge - synthesis, applications and prospects. New J. Chem. 34, 829-844 (2010).
  15. Strenkowska M., Kowalska J., Lukaszewicz M., Zuberek J., Su W.,. Rhoads R. E, Darzynkiewicz E., Jemielity J., Towards mRNA with superior translational activity: synthesis and properties of ARCA tetraphosphates with single phosphorothioate modifications, New J. Chem. 34, 993-1007 (2010).
  16. Wypijewska A., Bojarska E., Stepinski, J., Jankowska-Anyszka, M., Jemielity J., Davis, R.E., Darzynkiewicz E. Structural requirements for Caenorhabditis elegans DcpS substrates based on fluorescence and HPLC enzyme kinetic studies. FEBS J. 277, 3003-3013 (2010).
  17. Guranowski A, Wojdyla A.M., Zimny J., Wypijewska A., Kowalska J., Jemielity J., Davis, R.E., Bieganowski P. Dual activity of certain HIT-proteins: A. thaliana Hint4 and C-elegans DcpS act on adenosine 5 '-phosphosulfate as hydrolases (forming AMP) and as phosphorylases (forming ADP). FEBS Lett. 584, 93-98 (2010).
  18. Guranowski A., Wojdyla A.M., Zimny J., Wypijewska A., Kowalska J., Lukaszewicz M., Jemielity J., Darzynkiewicz E., Jagiello A., Bieganowski P. Recognition of different nucleotidyl-derivatives as substrates of reactions catalyzed by various HIT-proteins New J. Chem. 34, 888-893 (2010).

    2009
  19. Kowalska J., Lukaszewicz M., Zuberek J., Darzynkiewicz E., Jemielity J.; Phosphoroselenoate Dinucleotides for Modification of mRNA 5' End. ChemBioChem 10, 2469-2473 (2009).
  20. Rydzik A.M., Lukaszewicz M., Zuberek J., Kowalska J., Darzynkiewicz Z.M., Darzynkiewicz E., Jemielity J.; Synthetic dinucleotide mRNA cap analogs with tetraphosphate 5,5 bridge containing methylenebis(phosphonate) modification Org. Biomol. Chem. 7, 4763-4776 (2009).
  21. Zdanowicz A., Thermann R., Kowalska J., Jemielity J., Duncan K., Preiss T., Darzynkiewicz E., Hentze M.W.; Drosophila miR2 Primarily Targets the m7GpppN Cap Structure for Translational Repression. Molec. Cell 35, 881-888 (2009).
  22. Kowalska J, Lukaszewicz M, Zuberek J, Ziemniak M, Darzynkiewicz E, Jemielity J.; Phosphorothioate analogs of m7GTP are enzymatically stable inhibitors of cap-dependent translation. Bioorg. Med. Chem. Lett. 19, 1921-1925, (2009)
  23. Banerjee H., Palenchar J.B., Lukaszewicz M., Bojarska E., Stepinski J., Jemielity J., Guranowski A., Ng S., Wah D.A., Darzynkiewicz E., Bellofatto V.; Identification of the HIT-45 protein from Trypanosoma brucei as an FHIT protein/dinucleoside triphosphatase: Substrate specificity studies on the recombinant and endogenous proteins. RNA 15, 1554-1564, (2009).

    2008
  24. Tölle M, Jankowski V, Schuchardt M, Wiedon A, Huang T, Hub F, Kowalska J, Jemielity J, Guranowski A, Loddenkemper C, Zidek W, Jankowski J, van der Giet M.Adenosine 5'-Tetraphosphate Is a Highly Potent Purinergic Endothelium-Derived Vasoconstrictor. Circulation Research 108, 1100 - 1108, (2008).
  25. Kowalska J., Lewdorowicz M., Zuberek J., Grudzien-Nogalska E., Bojarska E., Stepinski J., Rhoads R.E., Darzynkiewicz E., Davis R.E., Jemielity J.; Synthesis and Characterization of mRNA Cap Analogs Containing Phosphorothioate Substitutions that Bind Tightly to eIF4E and are Resistant to the Decapping Pyrophosphatase DcpS. RNA 14, 1119-1131 (2008).
  26. Deshmukh MV, Jones BN, Quang-Dang D-U, Flinders J, Floor SN, Kim C, Jemielity J, Kalek M, Darzynkiewicz E, Gross JD.; mRNA Decapping Is Promoted by an RNA-Binding Channel in Dcp2. Molec. Cell 29, 324-336 (2008).

    2007
  27. Grudzien-Nogalska E, Jemielity J, Kowalska J, Darzynkiewicz E, Rhoads RE.; Phosphorothioate cap analogs stabilize mRNA and increase translational efficiency in mammalian cells. RNA 13, 1745-1755 (2007).
  28. Kowalska J, Lewdorowicz M, Darzynkiewicz E, Jemielity J.; A simple and rapid synthesis of nucleotide analogues containing a phosphorothioate moiety at the terminal position of the phosphate chain. Tetrahedron Lett. 48, 5475-5479 (2007).
  29. Grudzien-Nogalska E, Stepinski J, Jemielity J, Zuberek J, Stolarski R, Rhoads RE, Darzynkiewicz E.; Synthesis of anti-reverse cap analogs (ARCAs) and their applications in mRNA translation and stability. Method Enzymol. 431, 203-227 (2007).
  30. Darzynkiewicz ZM, Bojarska E, Kowalska J, Lewdorowicz M, Jemielity J, Kalek M, Stepinski J, Davis RE, Darzynkiewicz E.; Interaction of human decapping scavenger with 5 ' mRNA cap analogues: structural requirements for catalytic activity. J Phys-Condens Mat. 19 art. no. 285217 (2007)
  31. Zuberek J, Kubacka D, Jablonowska A, Jemielity J, Stepinski J, Sonenberg N, Darzynkiewicz E.; Weak binding affinity of human 4EHP for mRNA cap analogs. RNA 13, 691-697 (2007).
  32. Kowalska J, Lewdorowicz M, Zuberek J, Bojarska E, Stepinski J, Stolarski R, Darzynkiewicz E, Jemielity J.; Assignment of the absolute configuration of P-chiral 5'mRNA cap analogues containing phosphorothioate moiety. Nucleos. Nucleot. Nucl. Acids 26, 1301-1305 (2007).
  33. Jemielity J, Stolarski R, Darzynkiewicz E.; Synthesis of H-3 and C-13 labeled mRNA cap dinucleotides-useful tools for NMR, biochemical, and biological studies. Nucleos. Nucleot. Nucl. Acids 26, 1315-1319 (2007).
  34. Lewdorowicz M, Jemielity J, Kierzek R, Shapira M, Stepinski J, Darzynkiewicz E.; Solid-supported synthesis of 5 '-mRNA cap-4 from trypanosomatids. . Nucleos. Nucleot. Nucl. Acids 26, 1329-1333 (2007).
  35. Wierzchowski J, Pietrzak M, Stepinski J, Jemielity J, Kalek M, Bojarska E, Jankowska-Anyszka M, Davis RE, Darzynkiewicz E.; Kinetics of C elegans DcpS cap hydrolysis studied by fluorescence spectroscopy. Nucleos. Nucleot. Nucl. Acids 26, 1211-1215 (2007).
  36. Lewdorowicz M, Stepinski J, Kierzek R, Jemielity J, Zuberek J, Yoffe Y, Shapira M, Stolarski R, Darzynkiewicz E.; Synthesis of leishmania cap-4 intermediates, cap-2 and cap-3. Nucleos. Nucleot. Nucl. Acids 26, 1339-1348 (2007).
  37. Darzynkiewicz ZM, Bojarska E, Stepinski J, Jemielity J, Jankowska-Anyszka M, Davis RE, Darzynkiewicz E.; Affinity of dinucleotide cap analogues for human decapping scavenger (hdcps). Nucleos. Nucleot. Nucl. Acids 26, 1349-1352 (2007).

    2006
  38. 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. Bioorganic and Medicinal Chemistry 14, 3223-3230 (2006).
  39. Guranowski A, Starzyńska E, Pietrowska-Borek M, Jemielity J, Kowalska J, Darzynkiewicz E, Thompson MJ, Blackburn MG; Methylene analogues of adenosine-5'-tetraphosphate: their chemical synthesis and recognition by human and plant mononucleoside tetraphosphatases and dinucleoside tetraphosphatases. FEBS Journal 273, 829-838 (2006).
  40. Grudzien E, Kalek M., Jemielity J, Darzynkiewicz E, Rhoads RE; Differential inhibition of mRNA degradation pathways by novel cap analogs. Journal of Biological Chemistry 281, 1857-186 (2006).

    2005
  41. Westman B, Beeren L, Grudzien E, Stepinski J, Worch R, Zuberek J, Jemielity J, Stolarski R, Darzynkiewicz E, Rhoads RE, Preiss T; The antiviral drug ribavirin does not mimic the 7-methylguanosine moiety of the mRNA cap structure in vitro. RNA 11, 1505-1513 (2005).
  42. Kowalska J, Lewdorowicz M, Zuberek J, Bojarska E, Wojcik J, Cohen LS, Davis RE, Stepinski J, Stolarski R, Darzynkiewicz E, Jemielity J; Synthesis of mRNA cap analogues containing phosphorothioate moiety in 5',5'-triphosphate chain. Nucleos. Nucleot. Nucl. Acids, 24, 595-600 (2005).
  43. Jemielity J, Heinonen P, Lönnberg H, Darzynkiewicz E; Novel approach to solid phase chemical synthesis of oligonucleotide mRNA cap analogues, Nucleos. Nucleot. Nucl. Acids 24, 601-605 (2005).
  44. Kalek M, Jemielity J, Zuberek J, Grudzień E, Bojarska E, Cohen LS, Stepinski J, Stolarski R, Davis RE, Rhoads RE, Darzynkiewicz E; Synthesis and biochemical properties of novel mRNA 5' cap analogs resistant to enzymatic hydrolysis. Nucleos. Nucleot. Nucl. Acids 24, 615-621 (2005).
  45. Jemielity J, Pietrowska-Borek M, Starzynska E, Kowalska J, Stolarski R, Guranowski A, Darzynkiewicz E; Synthesis and Enzymatic Characterization of Methylene Analogs of Adenosine 5'-Tetraphosphate (p4A). Nucleos. Nucleot. Nucl. Acids 24, 589-593 (2005).
  46. Stepinski J, Zuberek J, Jemielity J, Kalek M, Stolarski R, Darzynkiewicz E; Novel Dinucleoside 5',5'-Triphosphate Cap Analogues. Synthesis and Affinity for Murine Translation Factor eIF4E. Nucleos. Nucleot. Nucl. Acids 24, 629-633 (2005).
  47. Kalek M, Jemielity J, Stepinski J, Stolarski R, Darzynkiewicz E; A Direct Method for the Synthesis of Nucleoside 5'-Methylenebis(phosphonate)s from Nucleosides. Tetrahedron Letters 46, 2417-2421 (2005).

    2004
  48. Lewdorowicz M, Yoffe Y, Zuberek J, Jemielity J, Stepinski J, Kierzek R, Stolarski R, Shapira M, Darzynkiewicz E; Chemical synthesis and binding activity of the trypanosomatid cap-4 structure. RNA 10, 1469-1478 (2004).
  49. Zuberek J, Jemielity J, Jablonowska A, Stepinski J, Dadlez M, Stolarski R, 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).

    2003
  50. Jemielity J, Fowler T, Zuberek J, Stepinski J, Lewdorowicz M, Niedzwiecka A, Stolarski R, Darzynkiewicz E, Rhoads RE. Novel "anti-reverse" cap analogs with superior translational properties. RNA 9, 1108-1122 (2003).
  51. Jemielity J, Stepinski J, Jaremko M, Haber D, Stolarski R, Rhoads RE, Darzynkiewicz E; Synthesis of novel mRNA 5 ' cap-analogues: Dinucleoside P-1, P-3-tri-, P-1, P-4-tetra-, and P-1, P-5-pentaphosphates. Nucleosides Nucleotides & Nucleic Acids 22, 691-694 (2003).
  52. Zuberek J, Jemielity J, Stepinski J, Lewdorowicz M, Niedzwiecka A, Haber D, Stolarski R, Rhoads RE, Darzynkiewicz E; Binding studies of eukaryotic initiation factor eIF4E with novel mRNA dinucleotide cap analogues. Nucleosides Nucleotides & Nucleic Acids 22, 1703-1706 (2003).
  53. Zuberek J, Jemielity J, Niedzwiecka A, Stepinski J, Wyslouch-Cieszynska A, Stolarski R, Darzynkiewicz E; Influence of the length of the phosphate chain in mRNA 5 ' cap analogues on their interaction with eukaryotic initiation factor 4E. Nucleosides Nucleotides & Nucleic Acids 22, 1707-1710 (2003)
  54. Kiraga-Motoszko K, Stepinski J, Niedzwiecka A, Jemielity J, Wszelaka-Rylik M, Stolarski R, Zielenkiewicz W, Darzynkiewicz E; Interaction between yeast eukaryotic initiation factor eIF4E and mRNA 5 ' cap analogues differs from that for murine eIF4E. Nucleosides Nucleotides & Nucleic Acids 22, 1711-1714 (2003)

    1998-2002
  55. Augustyniak W., Suchecki P., Jemielity J., Kański R., Kańska M.; Synthesis of tritium labelled isotopomers of L-tyrosine. Journal of Labeled Compounds and Radiopharmaceuticals 45 (2002) 559-567.
  56. Jemielity J., Kański R., Kańska M.; Synthesis of tritium labeled [3S-3H]- and [3R-3H]-L- Phenylalanine. Journal of Labeled Compounds and Radiopharmaceuticals 44 (2001) 295-304.
  57. Augustyniak W., Bukowski J., Jemielity J., Kański R., Kańska M.; Ezymatic synthesis of carbon-14 labeled isotopomers of L- phenylalanine. Journal of Radioanalytical Nuclear Chemistry 247 (2000) 371-374.
  58. Lewandowicz A, Jemielity J, Kańska M, Zon J, Paneth P.; Tritium secondary kinetic isotope effect on phenylalanine ammonia-lyase catalyzed reaction. Archives of Biochemistry and Biophysics 370 (1999) 216-221.
  59. Jemielity J., Kańska M., Kański R.; Enzymatic Synthesis of [1-13C]- and [1-14]-L-Phenylalanine. Isotopes in Environmental and Health Studies 34 (1998) 335-339.
Division of Biophysics, Institute of Experimental Physics, Faculty of Physics, University of Warsaw, ul. Pasteura 5, 02-093 Warszawa
Email: office@biogeo.uw.edu.pl :: Phone: +48 22 5532304