Biography of Dr. Krystyna Lesiak–Watanabe

Dr. Krystyna Lesiak-Watanabe was born on August 31, 1949, in Justynów near Łódź, Poland, to Anna and Stanisław Lesiak. She grew up with her younger brother Andrzej and they both attended the Łódź University of Technology (Politechnika Lódzka). She obtained M.Sc. degree in Chemical Engineering in 1972, and continued her chemistry education and research at the Centre of Molecular and Macromolecular Studies (CMMS), Polish Academy of Sciences in Łódź. She received her Ph.D. in Organic Chemistry in 1980, for her research work under the direction of Professor Dr. Wojciech Stec and a dissertation titled “Reactions of N-metallated Amidoethers of Tetracoordinated Phosphorus with Carbonyl, Thio- and Selenocarbonyl Compounds. Stereochemistry and Applications in the Synthesis of Phosphoric Acid Derivatives”. She continued her work at the CMMS laboratory headed by Professor Stec and contributed several novel synthetic pathways for biologically active phosphorothioates described in 13 scientific publications.1-5

In 1981, Dr. Lesiak joined the research group of Dr. Paul Torrence as a Visiting Fellow at the Laboratory of Chemistry, National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK) at the National Institutes of Health (NIH), Bethesda, MD. The initially intended post-doctoral training turned into a productive scientific career with over 40 scientific papers and patents published during the original research period of 1981-1985, and during her second tenure with Dr. Torrence in 1989-1991.6-29 Krystyna’s excellent chemistry skills combined with an inquisitive scientific mind resulted in syntheses of very unique biologically active nucleosides, nucleotides and oligonucleotides. Her work made possible much of the progress in the field of 2-5A and 2-5A-antisense oligonucleotides.20-36

The experience in oligonucleotide chemistry directed Krystyna’s career into studying DNA damage in mammalian cells upon exposure to the ionized radiation.37 These studies were carried at the University of Kansas Nuclear Reactor Center in collaboration with Dr. Kenneth T. Wheeler and supported by a grant from the US Department of Energy. The studies continued at the Wake Forest University Bowman Gray School of Medicine, Winston-Salem, NC, where Krystyna accepted position of the Research Associate Professor (1986-1989).

Krystyna’s experience in the synthesis of biologically active anti-cancer and anti-viral agents made a perfect match with her next appointment at the Laboratory of Biophysics at the Center for Biologics Research and Evaluation (CBER), Food and Drug Administration (FDA). She was in charge of the DNA research facility where is carried the research in collaboration with Dr. William Egan and also performed evaluation of the research and marketing applications for new biologic drugs (1991-1996).

In 1996, Dr. Lesiak joined a newly founded drug development company Codon where she was working on the prevention of skin cancer.38-43 She continued the anti-cancer and anti-viral research at the start-up company Pharmasset, Inc., where she held a position of a Senior Scientist. Her work was focused on the development of new anti-viral and anti-cancer medication and resulted in several patents and publications.44-47

It is very ironic that with a life-time dedication and significant contributions to the field of anti-cancer research she passed away at the top of her scientific career after succumbing to cancer on May 17, 2001. Krystyna was an accomplished scientist but also a great and kind person who always was ready to help others. Every new scientist who came to the NIH area, where she spent most of her research life could count on her help and generosity. She is truly missed by her friends, co-workers and many scientists who had the luck to know her. Krystyna’s husband, Dr. Kyoichi Watanabe wishes to extend this generosity into the future by establishing a scholarship fund in Krystyna’s name to help the young promising scientists of Polish origin to come to the USA and present their research work.


References to Selected Publications

  1. K. Lesiak, B. Uznański and W. J. Stec “Stereochemistry of the Michaelis-Becker reaction of cis– and trans-2-hydro-2-oxo-4-methyl-1,3,2-dioxaphosphorinan with methyl iodide”, Phosphorus, 6, 65-67 (1975).
  2. W. J. Stec and K. Lesiak “A novel route to aminoalkylphosphonic acid”, J. Org. Chem., 41, 3757-3759 (1976).
  3. K. Lesiak and W. J. Stec “The stereochemistry P-N bond cleavage in the Staudinger-Wittig type reaction of 2-anilido-3,4-dimethyl-5-phenyl-1,3,2-oxazaphospholidine-2-thione”, Z. Naturforsch., 33b, 782-785 (1978).
  4. K. Lesiak, Z. J. Leśnikowski, W. J. Stec and B. Zielińska “A new approach to syntheses of organic phosphoroselenoates and phosphorodiselenoates. Proof of absolute configuration assignment in enantiomers of cTMPS”, Pol. J. Chem., 53, 2041-2050 (1979).
  5. J. Baraniak, K. Lesiak, M. Sochacki and W. J. Stec “Stereospecific synthesis of cyclic adenosine 3′,5′-(SP)-cyclic[18O]-phosphate”, J. Am. Chem. Soc., 102, 4533-4534 (1980).
  6. H. Sawai, J. Imai, K. Lesiak, M. I. Johnston and P. F. Torrence, “Cordycepin Analogues of 2-5A and Its Derivatives: Chemical Synthesis and Biological Activity”, J. Biol. Chem., 258, 1671-1677 (1983).
  7. K. Lesiak and P. F. Torrence, “Synthesis and Biological Activity of a Fluorescent Analog of 2-5A”, FEBS Letters, 151, 291-296 (1983).
  8. M. I. Johnston, J. Imai, K. Lesiak and P. F. Torrence, “Immunochemical Analysis of the Structure of 2′,5′-Oligoadenylate”, Biochemistry, 22, 3453-3400 (1983).
  9. P. F. Torrence, J. Imai, K. Lesiak, J. Warinnier, J. Balzarini, and E. De Clercq, “Structure-Activity Relationships For and Potentiation of the Antimitogenic Activity of 2-5A Core Derived From 2-5A, A Mediator of Interferon Action”, J. Med. Chem., 26, 1674-1678 (1983).
  10. P. F. Torrence, J. Imai, K. Lesiak, J.-C. Jamoulle and H. Sawai, “Oligonucleotide Structural Parameters That Influence Binding of 2-5A to the 2-5A Dependent Endonuclease: Chain Length, Phosphorylation State and Heterocyclic Base”, J. Med. Chem., 27, 726-733 (1984).
  11. D. A. Eppstein, M. A. Vander Pas, B. B. Schryver, H. Sawai, K. Lesiak, J. Imai, and P. F. Torrence, “Cordycepin Analogs of ppp(A2’p)2A[2-5Al] Inhibit Protein Synthesis Through Activation of the 2-5A Dependent Endonuclease”, J. Biol. Chem., 260, 3666-3671 (1985).
  12. J. Imai, K. Lesiak, and P. F. Torrence, “Respective Roles of Each of the Purine N-6 Amino Groups of 5′-O-triphosphoryladenylyl-(2’→5′)adenylyl(2→5′)adenosine (2-5A) in Binding to and Activation of RNase L”, J. Biol. Chem., 260, 1390-1393 (1985).
  13. M. I. Johnston, J. Imai, K. Lesiak, H. Jacobsen, H. Sawai, and P. F. Torrence, “Antibody-Nucleic Acid Interactions. Monoclonal Antibodies Define Different Antigenic Domains in 2′,5′-Oligoadenylates”, Biochemistry, 24, 4710-4718 (1985).
  14. P. F. Torrence, J. Imai, J.-C. Jamoulle, A. Wong, and K. Lesiak, “Sequence-Specific 2′,5′-Oligonucleotides in the Molecular Dissection of the Biological Activity of 2-5A” in Williams, B. R. G., Silverman, R. H. (Eds.), The 2-5A System, Alan R. Liss, N. Y., pp 75-80 (1985).
  15. P. F. Torrence, J. Imai, J.-C. Jamoulle, and K. Lesiak, “Biological Activity of Molecular Dissections and Transformations of 2-5A”, Chem. Scripta, 26, 191-197 (1986).
  16. K. Lesiak, and P. F. Torrence, “Synthesis and Biological Activities of Oligo(8-bromoadenylates) as Analogs of 5′-O-Triphosphoadenylyl(2’→5′)adenylyl(2’→5′)adenosine”, J. Med. Chem., 29, 1015-1022 (1986).
  17. J.-C. Jamoulle, K. Lesiak, and P. F. Torrence, “Respective Role of Each of the Purine N7 Nitrogens of 5′-O-Triphosphoryladenylyl(2’→5′)adenylyl(2’→5′)adenosine in Binding to and Activation of the RNase L of Mouse Cells”, Biochemistry, 26, 376-383 (1987).
  18. K. Lesiak, and P. F. Torrence, “Purine 8-Bromination Modulates the Ribonucleage L Binding and Activation Abilities of 2′,5′-Oligoadenylates: Possible Influence of Glycosyl Torsion Angle”, J. Biol. Chem., 262, 1961-1965 (1987)
  19. P. F. Torrence, J. Kinjo, K. Lesiak, J. Balzarini, and E. De Clercq, “AIDS Dementia: Synthesis and Properties of a Derivative of 3′-Azido-3′-deoxythymidine (AZT) That May Become ‘Locked’ in the Central Nervous System”, FEBS Letters, 234, 135-140 (1988).
  20. K. Lesiak, E. De Clercq, and P. F. Torrence, “Adducts of Mannose 6-phosphate with 5-Iodo-2′-deoxyuridine and 2-5A as Potential Antiviral Agents”, Nucleosides and Nucleotides, 8, 1387-1398 (1989).
  21. N. Subramanian, T. Kovacs, K. Lesiak, P. F. Torrence, and J Lenard, “Inhibition of the RNA polymerase of Vesicular Stomatitis Virus by pppA2’p5’A and Related Compounds”, Antiviral Res., 13, 81-90 (1990).
  22. N. Nolan-Sorden, K. Lesiak, K. Bayard, P. F. Torrence, and R.A. Silverman, “Photochemical Crosslinking in Oligonucleotide-Protein Complexes Between a Bromine-Substituted 2-5A Analog and 2-5A-Dependent RNase By UV Lamp or Laser”, Anal. Biochem., 184, 298-304 (1990).
  23. P. S. Kedar, J. Abbots, T. Kovacs, K. Lesiak, P. F. Torrence, and S. Wilson, “Mechanism of HIV Reverse Transcriptase: Enzyme-Primer Interaction as Revealed Through Studies of a dNTP Analogue, 3-Azido-dTTP”, Biochemistry, 29, 3603-3611 (1990).
  24. F. J. Castora, C. E. Erickson, T. Kovacs, K. Lesiak, and P. F. Torrence, “2′,5′-Oligoadenylates Inhibit Relaxation of Supercoiled DNA by Calf Thymus DNA Topoisomerase I”, J. Interferon. Res., 11, 142-149 (1991).
  25. P. F. Torrence, D. Brozda, D. Alster, A. Pabuccuoglu, and K. Lesiak,
    “A New and Potent 2-5A Analogue Which Does Not Require A 5′-Polyphosphate To Activate Mouse L Cell RNase L”, Antiviral Res., 18, 275-289 (1992).
  26. K. Lesiak, S. Khamnei and P. F. Torrence, “2′,5′-Oligoadenylate-Antisense Chimeras: Synthesis and Properties”, Bioconjugate Chem., 4, 467-472 (1993).
  27. W. Xiao, M. R. Player, G. Li, K. Zhang, K. Lesiak and P. F. Torrence, “Synthesis and Characterization of Composite Nucleic Acids Containing 2′,5′-Oligoriboadenylate Linked To Antisense DNA”, Antisense Nucleic Acid Drug Devel., 6, 247-258 (1996).
  28. K. Lesiak and P. F. Torrence, “Efficient Functionalization of 2′,5′-Oligoadenylates With Sulfur”, Bioconjugate Chem. 8, 199-203 (1997).
  29. K. Lesiak, B. Uznanski, and P. F. Torrence, “The Solid Phase Synthesis of 2′,5′-Linked Oligoriboadenylates Containing 8-Bromoadenosine”, App. Biochem. Biotech., 67, 33-44 (1997).
  30. “Method of Cleaving Specific Sequences of RNA”, P. F. Torrence, K. Lesiak. R. Maitra, and R. H. Silverman, U. S. Serial No. 07/965,666, Filed Oct 21, 1992 and USSN # 08/123,449 (CIP of 07/965,666), filed Sept 17, 1993. PCT International Application PCT/US93/10103, filed Oct 20, 1994, published 28 April 1994, WO 94/09129. Granted 10 Dec 1996. Exclusive license to Ridgeway Biosystems.
  31. R. H. Silverman, A. Maran, R. K. Maitra, C. Waller, K. Lesiak, S. Khamnei, G. Li, W. Xiao, and P. F. Torrence, “2-5A Antisense Chimeras For Targeted Degradation of RNA”, in Antisense Technology: A Practical Approach, eds., Lichtenstein and Nellen, IRL Books, Oxford University Press, Oxford, England, 1997.
  32. P. F Torrence, K. Lesiak, J. Imai, M. 1. Johnston and H. Sawai, “2′,5′-Oligoadenylates: Their Role in Interferon Action and Their Potential as Chemotherapeutic Agents.” Nucleosides, Nucleotides and Their Biological Applications, J. L. Rideout. D. W. Henry, & L. M. Beacham, Eds., Academic Press, N. Y., pp. 67-115 (1983).
  33. P. F. Torrence, J. Imai, K. Lesiak, J.-C. Jamoulle, H. Sawai, J. Warrinnier, J. Balzarini and E. De Clercq, “Strategies in the Design of Oligo-nucleotides as Antiviral Agents”, NATO Advanced Study Institute Targets for the Design of Antiviral Agents, Plenum Press, N. Y., pp. 259-285 (1984).
  34. P. F. Torrence, W. Xiao, G. Li, K. Lesiak, S. Khamnei, A. Maran, R. Maitra, B. Dong, and R. H. Silverman, “2′,5′-Oligoadenylate antisense chimeras for the targeted ablation of RNA”, in Carbohydrates: Synthetic Methods and Advances in Antisense Therapeutics, Cook & Sanghvi, eds., ACS Symposium Series, 118-132 (1994).
  35. D. Krause, K. Lesiak, J. Imai, H. Sawai, P. F. Torrence and R. H. Silverman, “Structure-Activity Relationships of Analogs of 2-5A Determined Using the Core-Cellulose Assay Core 2-5A-Dependent RNase.” in Williams, B. R. G. and Silverman, R. H. (Eds.): The 2-5A System, Alan R. Liss, New York, pp 133-139 (1985).
  36. Acknowledgement Dedication in P. F. Torrence and L. D. Powell, “The Quest for an Efficacious Antiviral for Syncytial Virus”, Antiviral Chemistry & Chemotherapy, 13, 325-344 (2002).
  37. K. Lesiak and W.T. Wheeler, “Formation of α-deoxyadenosine in Polydeoxynucleotides Exposed to Ionized Radiation under Anoxic Conditions”, Radiation Res., 121, 328-337 (1990)
  38. D. A. Brown, W-Y. Ren, A. Khorlin, K. Lesiak, D. Conklin, K. A. Watanabe and M. M. Seidman, “Aliphatic and alicyclic diols induce melanogenesis in cultured cells and Guinea pig skin”, J. Investig. Dermatol., 110, 428-437 (1995).
  39. M. C. Bash, K. B. Lesiak, S. D. Banks, C. E. Frasch, “Analysis of Neisseria meningitidis class 3 outer membrane protein gene variable regions and type identification using genetic techniques.”, Infect. Immun., 63, 1484-1490 (1995).
  40. K. Lesiak, K. A. Watanabe, A. Majumdar, M. Seidman, K. Vanderveen, V. M. Goldstein and K. W. Pankiewicz, “Synthesis of nonhydrolyzable analogues of thiazole-4-benzamide and benzamide-adenine dinucleotide containing fluorine atom at the C2′ of adenine nucleoside: Induction of K562 differentiation and inosine monophosphate dehydrogenase inhibitory activity”, J. Med. Chem., 40, 2533-2538 (1997).
  41. K. Lesiak, K. A. Watanabe, A. Majumdar, J. Powell, M. Seidman, K. Vanderveen, B. M. Goldstein and K. W. Pankiewicz, “Synthesis of methylenebis(phosphonate) analogues of a mycophenolic acid – adenine dinucleotide: a glucuronidation–resistant analogue of NAD”, J. Med. Chem., 41, 618-622 (1998).
  42. K. Lesiak, K. A. Watanabe, J. George and K. W. Pankiewicz, “2-(4-nitrophenyl)ethyl methylenebis(phosphonate): a versatile reagent for the synthesis of nucleoside 5′-methylenebis(phosphonate)s”, J. Org. Chem., 63, 1906-1909 (1998).
  43. D. A. Brown, K. Lesiak, W-Y. Ren, K. L. Strzelecki and A. A. Khorlin, “Bicyclic monoterpenediols induce differentiation of S91 melanoma and PC12 pheochromocytoma cells by a cyclic guanosine monophosphate dependent pathway”, Pigment Cell Res., 12, 36-47 (1999).
  44. K. W. Pankiewicz, K. Lesiak-Watanabe, K. A. Watanabe and K. Malinowski, “Novel mycophenolic adenine methyenebis(phosphonate)s as potential immune suppressants”, Curr. Med. Chem., 6, 629-634 (1999).
  45. E. S. Gibson, K. Lesiak, K. A. Watanabe, L. J. Gudas and K. W. Pankiewicz “Synthesis of a novel C-nucleoside, 2-amino-7-(2-deoxy-β-d-erythro-pentofuranosyl)-3H,5H-pyrrolo[3,2-d]pyrimidine-4-one (2′-deoxy-9-deazaguanosine)”, Nucleosides Nucleotides, 18, 363-376 (1999).
  46. K. W. Pankiewicz and K. Lesiak-Watanabe, “Novel mycophenolic adenine methylenebis(phosphonate)s as potential anticancer agents and inducers of cell differentiation”, Nucleosides Nucleotides, 18, 927-932 (1999).
  47. K. W. Pankiewicz, K. B. Lesiak-Watanabe, K. A. Watanabe, S. E. Patterson, H. N. Jayaram, J. A. Yalowitz, M. D. Miller, M. Seidman, A. Majumdar, G. Prehna and B. M. Goldstein, “Novel mycophenolic-adeninebis(phosphate) analogues as potential differentiation agents against human leukemia”, J. Med. Chem., 45, 703-712 (2002).