Nikolajs Sjakste

 Born: May 11, 1955, Riga, Latvia

Interests:

• Cell nucleus structure
• Nitric oxide in pharmacology
• Proteasomal gene polymorphism

Brief description of main results:

1. Changes of DNA interactions with nuclear matrix proteins were revealed during transition of cells from proliferation to quiescence (1978 – 1991).
2. Physiological role of DNA strand breaks was elucidated in several models (1983-1991).
3. Asymmetric transcription in the chicken alpha-globin gene domain was characterized; two formerly unknown genes were described (1993 – 1998).
4. Gene domain structure of proteasomal PSMA 6 gene was studied, polymorphism of the gene was studied, and association of certain alleles to type 2 diabetes, Graves ’ disease and juvenile idiopathic arthritis was revealed (1999 – 2004).
5. Increase of the nitric oxide production rate during action of volatile halogenated anaesthetics was investigated, mechanism of the phenomenon were studied (1998 – 2004).
6. Role of the nitric oxide in the mechanism of action of an antiischemic drug mildronate created in Latvia was revealed (2000 – 2004).
7. A chromatin site resistant to apoptotic fragmentation was revealed in the chicken alpha-globin gene. Mechanism of the phenomenon is under study.

Languages: Latvian, Russian, English, French (Italian, German)

Education:

• 2nd Moscow Medical Institute, Medico-Biological faculty, Department of Biophysics, Diploma with Distinction (1978).
• Post-graduate course in Cancer Research Center, Moscow, Russia (1980 – 1983).
• Degree of Candidate of Biological Sciences (Ph. D.), 1984, Cancer Research Center, Moscow, Russia.
• Degree of Doctor of Biological Sciences (Dr. habil. boil.), 1992, Institute of Experimental Medicine, St.-Petersburg, Russia.

Experience:

• 1983 -1990; Junior (till 1989) and Senior Researcher in the Cancer Cell Chemistry Laboratory, Institute of Experimental and Clinical Medicine, Riga, Latvia.
• 1990- Head of the Biochemistry Team, Latvian Institute of Organic Synthesis, Riga, Latvia.
• 1995 - 1998 Associated Researcher in the Biochemistry of Differentiation Laboratory, Institut Jacques Monod, Paris, France
• 1998 - Professor of Medical Biochemistry and Medical Genetics. University of Latvia, Faculty of Medicine.

Honours and awards

• Corresponding Member, Latvian Academy of Sciences, 2005
• S. Hiller Medal awarded by the Research Council of the Latvian Institute of Organic Synthesis, 2005

Professional Activities and Memberships

• Expert of the Promotion Council “ Medicine and Biology” in the University of Latvia
• Secretary of the Professorship Council in the medicine branch, University of Latvia
• 2002 – 2004 – Member of the Expert commission for evaluation of joint scientific projects in the University of Latvia.
• 2005 – Participant of the panel „Biosciences 2” of the Research Council for Biosciences and Enviroment of the Academy of Finland
• Member of the New York Academy of Sciences since 1996.

Representative Publications:

>170 scientific publications including ~ 100 full articles in international peer-reviewed journals, 1 monograph, 1 author’s certificate, 5 popular articles.

1. Chromosomal aberrations and molecular weight of single – stranded DNA fragments in embryonic fibroblasts of 101/H and CBA mice. - Bull. Exp. Biol. Med. – Engl. Tr., 1982, Vol. 92, No 9, pp. 1231 – 1233.
2. A.V. Lichtenstein, N.I.Sjakste, M.M.Zaboykin, V. S.Shapot. Rearrangements of DNA – protein interactions in animal cells coupled with cellular growth – quiescence transitions. - Nucleic Acids Research, 1982, Vol. 10, No 3, pp. 1127 – 1145.
3. N.I.Sjakste, M.M.Zaboikin, E.A.Erenpreisa, A.V.Lichtenstein, V.S.Shapot. Analysis of cellular nucleoproteins with nucleoprotein – celite chromatography. III. Two types of interactions between DNA and nuclear matrix. - Mol. Biol. – Engl. Tr., 1985, Vol. 19, No 5, P. 1, pp. 1007 – 1016.
4. N.I.Sjakste, T.G.Sjakste, N.D.Zaleskaya. Reversible accumulation of double – and single – strand breaks during the transition of cells into the resting state. - Bull. Exp. Biol. Med. – Engl. Tr., 1986, Vol. 102, No 8, pp. 1059 – 1061.
5. N.I.Sjakste. Role of DNA breaks in the regulation of processes of cell proliferation, differentiation and aging. - Soviet Journal of Developmental Biology – Engl. Tr., 1987, Vol. 18, No 3, pp. 139 – 146.
6. N.I.Sjakste. Interaction of various groups of the nuclear matrix proteins with DNA. - Biochemistry – Engl. Tr., 1988, Vol. 53, No 2, P. 1, p. 219.
7. N.I.Sjakste, T.G.Sjakste. Heterogeneity of the deproteinization – resistant proteins on the tightness of the association with DNA. - Bull. Exp. Biol. Med. – Engl. Tr., 1990, Vol. 110, No 8, pp. 1009 – 1109.
8. N.I.Sjakste, A.V.Budylin, T.G.Sjakste. Disconnection of DNA domains in quiescent and differentiating cells. - In: Nuclear Structure and Functions, N.Y., 1990, pp. 365 – 369.
9. A.V.Lichtenstein, M.M.Zaboykin, N.I.Sjakste, R.P.Alechina. Differential dissociation of chromatin digests: a No vel approach revealing a hierarchy of DNA – protein interactions within chromatin domains. - J.Cell Sci., 1991, Vol. 99, pp. 503 – 513.
10. P.Pasero, N.Sjakste, C.Blettry, C.Got, M.Marilley. Long – range organization and sequence – directed curvature of XeNo pus laevis satellite 1 DNA. - Nucleic Acids Research, 1993, Vol. 21, No 20, pp. 4703 – 4710.
11. N.I.Sjakste, T.G.Sjakste. Enzyme activities of nuclear matrix. - Biochemistry, Moscow, 1994, Vol. 50, No 11, pp. 1239 – 1246.
12. N.Sjakste, L.Baumane, D.Meirena, L.Lauberte, M.Dzintare, I.Kalvinš. Drastic increase in nitric oxide content in rat brain under halothane anesthesia revealed by EPR method. - Biochem Pharmacol, 1999, Vol. 58, No 12, pp. 1955 – 1959.
13. N.Sjakste, T.Sjakste, G. Stacey, B. Bolton and A. Doyle Distribution of tightly – bound proteins along the chicken alpha – globin gene.  - Proc. Latv. Acad. Sci., Sect B, 1999, Vol. 53, No 1, pp. 5 – 11.
14. N.Sjakste, O.Iarovaia, S.Razin, G.Linares – Cruz, T.Sjakste, V. Le Gac, Z. Zhao and K. Scherrer. A No vel gene is transcribed in the chicken a – globin gene domain in the direction opposite to the globin genes. - Mol. Gen. Genet., 2000, Vol. 262, pp. 1012 – 1021.
15. N.I.Sjakste, T.G.Sjakste. Transcription factors and the nuclear matrix. - Molecular Biology, 2001, Vol. 35, No 5, pp. 627 – 635.
16. O.Iarovaia, S.Razin, G.Linares – Cruz, N.Sjakste, K.Scherrer. In chicken leukemia cells globin genes are fully transcribed but their RNAs are retained in the perinucleolar area. Exp. Cell Res., 2001, V. 270, No. 2, P. 159 – 65.
17. T.Sjakste, N.Sjakste, K.Scherrer. Exon/intron organisation of the human proteasome PROS – 27 gene. - DNA Sequence, 2001, Vol 12, Issue 4, pp. 261 – 265.
18. L. Baumane, M. Dzintare, L. Zvejniece, D. Meirena, L. Lauberte, V. Sile, I. Kalvinsh, N.Sjakste. Increased synthesis of nitric oxide in rat brain cortex due to halogenated volatile anesthetics confirmed by EPR spectroscopy.- Acta Anaesthesiologica Scandinavica, 2002, Vol. 46, No 4, pp. 378 – 383.
19. M.Dzintare, L.Baumane, D.Meirena, L.Lauberte, I.Kalvinsh, N.Sjakste. Involvement of nitric oxide production in the mildronate mechanism of action. - Pharmacology Reviews and Communications, 2002, Vol. 12, No 3, pp. 163 – 170.
20. T.Sjakste, L.Lauberte, Y.Collan, M. – L.Savontaus, A.Bajare, K.Scherrer, N.Sjakste. Identification of an intronic TG repeat polymorphism in the human proteasome core particle PROS – 27 gene. - DNA Seq., 2002, Vol. 13, No 3, pp. 139 – 143.
21. N.I. Sjakste, T.G. Sjakste. Structure of globin gene domains in mammals and birds. - Russian Journal of Genetics, 2002, Vol. 38, No 12, pp. 1342 – 1358.
22. N.Sjakste, T.Sjakste, U.Vikmanis. Role of the nuclear matrix proteins an malignant transformation and cancer diagnosis. Experimental Oncology, 2004, V.26, No3, P.170-178.
23. N.Sjakste, L.Baumane, J. – L.Boucher, M.Dzintare, D.Meirena, J.Sjakste, L.Lauberte, I.Kalvinsh. Effects of gamma – butyrobetaine and mildronate on nitric oxide production in lipopolysaccharide – treated rats. - Basic & Clinical Pharmacol. Toxicol., 2004, Vol. 94, pp. 37 – 41.
24. N.Sjakste, A.Kleschyov, J. – L.Boucher, L.Baumane, M.Dzintare, D.Meirena, J.Sjakste, L.Lauberte, K.Sydow, T.Münzel, I.Kalvinsh. Endothelium- and Nitric Oxide – Dependent Vasorelaxing Activities of Gamma – Butyrobetaine Esters: Possible Link to the Anti – Ischemic Activities of Mildronate. - Eur. J. Pharmacol., 2004, Vol. 495, Issue 1, pp. 67 – 73.
25. N.Sjakste. Site – specific excision or protection of an alpha a globin gene genomic site in apoptotic transformed chicken erythroblasts. - Cell Mol. Biol. Lett., 2004, Vol. 9, No. 3, pp. 429 – 437.
26. T.Sjakste, E.Eglite, A.Sochnev, M.Marga, V.Pirags, Y.Collan, N.Sjakste. Microsatellite genotyping of chromosome 14q13.2 – 14q13 in the area of proteasomal PSMA6 gene on association with Graves’ disease in the Latvian population.- Immunogenetics, 2004, Vol.56, No 4, pp. 238-243.
27. Sjakste T, Roder M, Labeikyte D, Bagdoniene L, Levina A, Juodka B, Sjakste N. Distribution of tight DNA-protein complexes along the barley chromosome 1H, as revealed by microsatellite marker analysis. - Cell Mol Biol Lett. 2005, V10, No 1, P. 49-59.
28. N.Sjakste, T.Sjakste. Nuclear matrix proteins and hereditary diseases. - Russian Journal of Genetics, 2005, V. 41, No3, P.221-226.
29. Sjakste N, Sjakste J, Boucher JL, Baumane L, Sjakste T, Dzintare M, Meirena D, Sharipova J, Kalvinsh I. Putative role of nitric oxide synthase isoforms in the changes of nitric oxide concentration in rat brain cortex and cerebellum following sevoflurane and isoflurane anaesthesia. - Eur J Pharmacol. 2005, V. 513, No 3, P.193-205.
30. Sjakste N, Gutcaits A, Kalvinsh I. Mildronate: An antiischemic drug for neurological indications. - CNS Drug Reviews. 2005, V.11, No 2, P. 151-168.
31. A.L. Kleschyov; S Strand, S. Schmitt, D. Gottfried,  M. Skatchkov, N. Sjakste, A. Daiber, V. Umansky, T. Munzel. Dinitrosyl-iron triggers apoptosis in Jurkat cells despite overexpression of Bcl-2. - Free Radic. Biol. Med.,  2006, 40(8), pp. 1340-1348.
32. Sjakste N and Kalvinsh I.  Mildronate: an antiischemic drug with multiple indications.- Pharmacologyonline,  2006,  1: pp. 1-18.
33. Sjakste N., Rumba I. and Sjakste T. Various chromatin and nuclear matrix proteins as autoantigens: a possible link to the protein degradation mechanisms. - Med Hypotheses Res., 2006, 3,  p. 655-677.
34. Paeglis R., Bagucka K., Sjakste N., and Lacis I. Maximizing reading: pattern analysis to describe points of gaze. -  Proc.SPIE , V.6315. Mathematics of Data/Image Pattern Recognition, Compression, and Encryption with Applications IX, Gerhard X. Ritter, Mark S. Schmalz, Junior Barrera, Jaakko T. Astola, Editors, 63150R (Aug 25, 2006)
35. N.Sjakste, T.Sjakste. Possible involvment of DNA strand breaks in regulation of cell differentiation. - Eur. J. Histochem., 2007, vol. 51, pp. 81-94.
36. N.Sjakste, V.G.Andrianov, J.L.Boucher, et al. Paradoxical effects of two oximes on nitric oxide production by purified NO synthases, in cell culture and in animals. - Nitric Oxide, 2007, vol. 17, N 3/4, p. 107-114.
37. K.Bielskiené, L.Bagdoniené, B.Juodka, M.Lipinski, T.Sjakste, Y.S. Vassetzky and N.Sjakste. Transcription- and apoptosis-dependent long-range distribution of tight DNA-protein complexes in the chicken alpha globin gene. - DNA Cell Biology, 2008, 27 (11): 615-621.
38. Sjakste T., Bielskiené K., Röder M., Sugoka O., Labeikyte D., Bagdoniené L., Juodka B., Vassetzky Y., Sjakste N.  Development-dependent changes in the thight DNA-protein complexes of barley on chromosome and gene level. - BMC Plant Biology, 2009, 9: 56.
39. Bagdoniené L., Labeikyte D., Kalvins I., Borutinskaite V., Prokofjevs A., Trapencieris P., Juodka B., Sjakste N.  Rat serum carboxylesterase partly hydrolyses gamma-butyrobetaine esters. - Arh High Rada Toksikol., 2009, 60 (2): 147-156.

Participation in international conferences:

    Oral or poster presentations in 13 conferences in 1998-2006.

International collaboration, stays in foreign laboratories

• 1998 - 1999; Institut Jacques Monod, Universite Paris VII, Laboratoire de Biochimie de Differentiation, Paris, France.(Surpervisor - Klaus Scherrer). “red post” of CNRS.2000, 2001, 2003; Department of Pathology, University of Turku, Turku, Finland, Supervisor - Yrjö Collan – Supported by the Nordic Council of Ministers
• 2002, 2003 – Laboratory of Pharmacological and Toxicological Chemistry and Biochemistry, University Paris V, France, (Supervisor - Jean-Luc Boucher). Supported by Ministry of Foreign Affairs of France and “Osmose” program.
• 2002 – Department of Cardiology, University Hospital Eppendorf, Hamburg, Germany. (Supervisor – Thomas Münzel). DAAD fellowship.
• 2003, 2004 – Department of Biochemistry and Biophysics, University of Vilnius, Lithuania. (Supervisor – Benediktas Juodka). Supported by CEBIOLA program.

1. 1999 – 2003 “Role of nitrogen oxide in mechanism of action of anesthetics and antiischemic drugs” – sponsored by the Latvian Council of Science, grant No 01.0042
2. 2000 - 2004“Polymorphism of the proteasomal protein PROS-27 genome domain and its linkage to human pathology”, part of the joint project “Studies of the Latvian genofund and their application to diagnostics and prophylaxis of human pathologies” sponsored by the Latvian Council of Science, grant No 01.0023.111.
3. 2004 – „Pathological production of nitric oxide, possibilities of its pharmacological correction” – sponsored by the Latvian Council of Science, grant No 04.1317.
4. 2004 – „Differentiation and apoptosis-related structural changes in the chicken alpha-globin domain chromatin” - sponsored by the Latvian Council of Science, grant No 04.1280.

    International

1. 1996-1998 Responsible for the Supplementary Agreement "Tightly bound proteins in differentiation and malignancy" to European Community project "European Animal Cell Collection". In collaboration with Center for Applied Microbiology and Research, Salisbury, U.K.
2. 2000/2001 “Study of genetic restriction fragment length and microsatellite polymorphism on chromosome 14 and PROS-27 gene and its probable linkage to human diseases”– a Nordic Network Grant Scheme grant awarded by the Nordic Council of Ministers, in collaboration with Turku University (Finland) and Karolinska Hospital (Sweden), Co-ordinator..
3. Since 2000 – “Regulation of NO production by anaesthetics assayed in vivo and in vitro” – sponsored by the French Government and “ Osmose” program, in collaboration with Universite Paris V, Paris, France, Co-ordinator.
4. 2002/2003 “Diabetes genetics studies in Nordic countries and Latvia” – a Nordic Network Grant Scheme grant awarded by the Nordic Council of Ministers, in collaboration with Turku University (Finland) and Wallenberg Laboratory (Malmö, Sweden) Co-ordinator.
5. 2004 – “Quality and extent of the molecular biology teaching on different levels of medical education”. “Neighbour Plus Program project, supported by the Nordic Council of Ministers. Network formed by universities from Latvia, Lithuania, North-Western Russia, Finland, Sweden, Norway and Denmark. Co-ordinator.
6. 2005 - Joint Taiwan-Latvian-Lithuanian project „Purification and characterization of the gamma-butyrobetaine esterase”. Co-ordinator.

Last update 06.11.2009