Personnel

Research

Biomolecule group (BMG)

Biomolecule group is specialized to the use of synthetic peptides, their derivatives, recombinant proteins viruses and nanoparticles in basic and applied research. The aim of the group is to combine organic chemistry to advanced biomedicinal research. The scientific projects in BMG vary from synthesis and structural analyses (NMR) of the bioactive peptides to the pre-clinical imaging of tumors and brain injury's in laboratory animal models. BMG has close collaboration with Small Animal Imaging Center located in AIV Institute, University of Kuopio, producing i.e. tracer compounds for imaging (http://www.uku.fi/aivi/services/biu/index.shtml). In addition BMG has a broad scientific network, which includes Finnish and European academic research groups as well as bioindustrial companies. BMG provides interesting projects for the students in the field of physics, chemistry, biochemistry and biomedicine. Students are introduced to the field of interest trough the scientific projects after which the graduate work can be tailored for each student.

The core of the BMG is solid phase synthesis laboratory, where synthetic peptides and their derivatives are produced. Synthesis is automatic allowing the parallel synthesis of several peptides. In addition there is HPLC systems for purification and analyses, ABI ESI/MALDI mass spectrometer (scientist in charge, Jukka Häyrinen, Dept. Biochemistry), testing laboratory for vitro analyses of bioactive molecules and radio laboratory for labelling molecules, viruses, nanoparticles and cells for biodistribution studies in experimental animals. Imaging centre, located in AIV institute of University of Kuopio, consist of two MRI units (Magnetic Resonance Imaging, leader Dr. Olli Gröhn), and one SPECT / CT unit (leader Dr. Ale Närvänen). All equipments are suitable for small animal imaging.

PRO GRADU -PAIKKA TARJOLLA

Haetaan gradun tekijää, aiheena angiogeneesi, lymfangiogeneesi sekä kasvainsolujen invaasio metastaattisissa imusolmukkeissa munasarja- ja keuhkosyöpämalleissa. Tutkimus tehdään valmiista kudosnäytteistä erilaisia immunohistokemiallisia menetelmiä hyödyntäen. Tutkimustuloksista on tarkoitus kirjoittaa myös kansainvälinen tieteellinen julkaisu, johon tekijä saa nimensä mukaan.

Lisätietoja: Tuulia Huhtala (tuulia.huhtala@uef.fi, p. 040 505 6823)   

BMG group

• Dr. Ale Närvänen, group leader
• M.Sc. Miikka Pakkala, Ph.D. student. Organic chemist: peptide synthesis (peptide libraries), structure analyses (NMR) and mass spectrometry
• M.Sc. Tuulia Huhtala, Ph.D. student. biochemist: radiochemistry, animal experiments, SPECT/CT imaging.
• M.Sc. Janne Weisell, Ph.D. student biochemist: peptide synthesis (peptide libraries), mass spectrometry, polyamine research.
• M.Sc. Jussi Rytkönen, Ph.D. student biochemists: nanoparticle research, peptide synthesis (peptide libraries), mass spectrometry

Scientific Projects and collaborators

Nanoparticles: A new three years project funded by Finnish Academy started in the beginning of 2009. The aim of the project is to develop new silicon based mesoporous nanoparticles for therapeutic purposes. Using targeting molecules like monoclonal antibodies or synthetic peptides on the surface of the nanoparticles the homing properties to target tissue or cells are enhanced.

Academic Consortium :

Docent Jarno Salonen, Department of Physics, University of Turku.
Docent Ale Närvänen, Department of Biosciences and AIV Institute, University of Kuopio.

IMAGING

MRI: We have used artificial cell receptors in vitro in cell cultures and in vivo in laboratory animals and studied their intake of the magnetic particles (diameter 50 nm) by MRI. In addition we have labelled Baculoviruses with same construct and studied the biodistribution of the complex in rat brain.

Mäntylä T. Hakumäki J. Huhtala T. Lehtolainen P. Närvänen A. Ylä-Herttuala S. Targeted magnetic resonance imaging of Scavidin-receptor in human umbilical vein endothelial cells in vitro. Magn Reson Med. 55(4):800-4, 2006.

Räty J. Liimatainen T. Wirth T. Airenne K. Huhtala T. Ihalainen T. Hamerlynck E. Vihinen-Ranta M. Närvänen A. Ylä-Herttuala S. Hakumäki J. Magnetic resonance imaging of viral particle biodistribution in vivo. Gene Ther. 2006 (in press).

SPECT/CT: The effects of human cord blood cells (HUCB) on sensorimotor, cognitive, and histological outcome in rats following transient middle cerebral artery occlusion (MCAO) has been studied in the Department of Neuroscience and Neurology. We have studied the acute whole body distribution of intravenously administered HUCB cells, labelled with Indium-111-oxine, by SPECT/CT. The biodistribution of radiolabelled baculoviruses and lentiviruses have been studied in rats.

Collaborators

Dr. Jukka Jolkkonen, Department of Neuroscience and Neurology, University of Kuopio
Seppo Ylä-Herttuala MD, prof. AIV Institute, Dept. of Biotechnology and Molecular Medicine. Univ. of Kuopio.

Mäkinen S. Nystedt J. Kekarainen T. Huhtala T. Liimatainen T. Närvänen A. Laine J. Jolkkonen J. Human umbilical cord blood cells do not improve sensorimotor or cognitive outcome following transient middle cerebral artery occlusion in rats Brain Res. (accepted).

Lappalainen R, Narkilahti S, Huhtala T, Liimatainen T, Suuronen T, Närvänen A, Suuronen R, Hovatta O, Jolkkonen J. Intravenously injected 111In-labeled stem cells accumulate in to internal organs in rats after middle cerebral artery occlusions detected with SPECT imaging. Neuroscience Letters 440: 246-250, 2008.

Räty J. Liimatainen T. Huhtala T. Kaikkonen M. Airenne K. Laitinen O. Hakumäki J. Närvänen A. Ylä-Herttuala S. SPECT/CT imaging of Baculovirus biodistribution in rat. Gen. Ther. 14(12):930-938, 2007.

Kaikkonen MU, Viholainen J, Närvänen A, Ylä-Herttuala S, Airenne KJ. Targeting and purification of metabolically biotinylated Baculovirus. Human gene Ther.19:589-600, 2008.

Kaikkonen MU, Lesch HP, Pikkarainen J, Räty JK, Vuorio T, Huhtala T, Taavitsainen M, Laitinen T, Tuunanen P, Gröhn O, Närvänen A, Airenne KJ, Ylä-Herttuala S. (Strept)Avidin-displaying Lentiviruses as Versatile Tools for Targeting and Dual-imaging of Gene Delivery (submitted).

Cancer research

Targeting molecules: One of the research focus in molecular medicine is the development of molecules, homing specifically to the tissues or cells with pathological alterations. Our research group has studied the homing properties of monoclonal antibodies and synthetic peptides to ovarian carcionoma and glioblastoma, respectively. We have been able to image the specific accumulation of the molecules to the tumor tissue using SPECT/CT imaging unit (manuscripts under preparation).

Collaborators:

Seppo Ylä-Herttuala MD, prof. AIV Institute, Dept. of Biotechnology and Molecular Medicine. Univ. of Kuopio.
Jouko Vepsäläinen Ph.D, prof. Dept. of Biosciences, Univ. of Kuopio.
Pirjo Laakkonen Ph.D, prof. Dept. of Biotechnology and Molecular Medicine. Univ. of Kuopio and Molecular Cancer Biology Research Program Institute of Biomedicine. Univ. of Helsinki.
Kari Alitalo, MD, prof. Molecular Cancer Biology Research Program and Institute of Biomedicine. Univ. of Helsinki. Tumor models.
Alex Khomutov, Ph.D. prof, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia. Organic and medicinal chemistry.

Kallikreins: Two prostate-specific proteases, KLK2 and KLK3 (PSA), are widely used as tumor markers in prostate cancer. By using phage display techniques, peptides binding specifically to the active forms of KLK2 and KLK3 have been characterized in the Department of Clinical Chemistry, University of Helsinki. We have synthesised corresponding peptides analogs, studied the prerequisities of the binding of these peptides to the target molecule and their 3-dimensional structure by NMR. Furthermore we have tested KLK3 specific peptides in animal models by SPECT/CT in order to evaluate their use as imaging molecules.

Collaborators

Prof. Ulf-Håkan Stenman, Department of Clinical Chemistry, University of Helsinki
Docent Hannu Koistinen, Department of Clinical Chemistry, University of Helsinki

Leinonen J. Wu P. Koivunen E. Närvänen A. Stenman U-H. Development of novel peptide ligands modulating the enzyme activity of prostate-specific antigen. Scand.J.Clin.Lab.Invest 233:59-64, 2000.

Wu P. Stenman U.-F. Pakkala P. Närvänen A. Leinonen J. Separation of enzymatically active and inactive forms of prostate specific antigen (PSA) with peptide affinity chromatography. Prostate 58(4):345-53, 2004.

Pakkala M. Jylhäranta A. Wu P. Leinonen J. Stenman U.H. Santa H. Vepsäläinen J. Peräkylä M. Närvänen A. Conformational and biochemical analysis of the cyclic peptides which modulate serine protease activity. J. Pept. Sci. 10: 439-447, 2004.

Zhu L, Koistinen H. Wu P, Narvanen A. Schallmeiner E. Fredriksson S. Landegren U. Stenman UH. A sensitive proximity ligation assay for active PSA. Biol Chem. 387(6):769-72., 2006.

Hekim C. Leinonen J. Närvänen A. Koivunen E. Väisänen V. Stenman U-H. Novel peptide inhibitors of human kallikrein 2 (hK2). J. Biol. Chem. 281:12555-12560, 2006.

Pakkala M. Hekim C. Soininen P. Leinonen J. Koistinen H. Weisell J. Stenman U-H. Vepsäläinen J. Närvänen A. Activity and stability of human kallikrein hK2 specific linear and cyclic peptides. J. Pept. Sci. 13(5):348-353, 2007.

Koistinen H, Närvänen A, Pakkala, P, Hekim C, Aaltonen J, Zhu L, Laakkonen P, Stenman -H Development of peptides specific for hK2 and PSA review Biol. Chem. 389: 633-642, 2008.

Directed peptide libraries and peptidomimetics: We are developing directed peptide libraries and peptidomimetics in order to improve affinity and stability of the molecules for in vivo use. We have optimize the protein C kinase substrate by using synthetic peptide library. Peptide library provides promising method for design of substrate-site directed peptide or peptidomimetic inhibitors of protein kinases. The stability of synthetic peptides in vivo may not be optimal. Using peptidomimetic approach we have developed new building blocks for PSA specific peptides (manuscript under preparation).

Collaborators

Erik Wallen (Ph.D.), University of Helsinki
Prof. Kristina Luthman, Department of Medicinal Chemistry, Göteborg university.

Loog M. Ek B. Oskolkov N. Närvänen A. Järv J. Ek P. Screening for the optimal specificity profile of protein kinase C using electrospray mass-spectrometry. J. Biomol. Screening. 320-328, 2005.

Viral serology: Hanta viruses are group of viruses causing severe hemorrhagic fever (Hanta virus and Dobrava virus) or milder neprhopatia epidemica (Puumala virus). We have developed, in collaboration with the Department of Virology University of Helsinki and Reagena Inc, rapid tests for the diagnosis of the acute phase infection of Hanta viruses. Today we are developing both rapid tests and serological micro chips for detection of the viral infections.

Collaborators

Dr. Helena Sirola, néé Hujakka, Reagena Inc. Kuopio.
Dr. Ilpo Kuronen, Reagena Inc. Kuopio. Dr.
Ilkka Julkunen, Public Health Laboratories, Helsinki.
Prof. Antti Vaheri, prof. Olli Vapalahti and prof. Klaus Hedman University of Helsinki.

Hujakka H. Koistinen V. Eerikäinen P. Kuronen I. Mononen I. Parviainen M. Lundkvist Å. Vaheri A. Närvänen A. Vapalahti O. A New Immunochromatographic Rapid Test for Diagnosis of Acute Puumala virus Infection. J.Clin.Microbiol. June 39(6): 2146-2150, 2001.

Hujakka H. Koistinen V. Eerikäinen P. Kuronen I. Laatikainen A. Kauppinen J. Vaheri A. Vapalahti O. Närvänen A. Comparison of a new immunochromatographic rapid test with a commercial EIA for the detection of Puumala virus specific IgM antibodies. J.Clin.Virol. 23(1-2):79-85, 2001.

Hujakka H. Koistinen V. Kuronen I. Eerikäinen P. Parviainen M. Lundkvist Å. Vaheri A. Vapalahti O. Närävnen A. Diagnostic rapid tests for acute hantavirus infections:specific tests for Hantaan, Dobrava and Puumala viruses versus a hantavirus combination test. J.Virol. Meth. 108:117-122, 2003.

Sirola H, Kallio ER, Koistinen V, Kuronen I, Lundkvist Å, Vaheri A, Vapalahti O, Henttonen H, Närvänen A. Rapid field test for detection of hantavirus antibodies in rodents. Epidemiol. and Infect. 132(3):549-553, 2004.

Immunology: Professor Tuomas Virtanen has a long experience in the research of cow and dog allergens and their T-cell epitopes. Our laboratory has produced experimental T-cell epitopes by synthesizing short overlapping peptides covering the amino acid sequence of allergen proteins.

Prof. Tuomas Virtanen, Department of Clinical Microbiology, University of Kuopio

Saarelainen S, Zeiler T, Rautiainen J, Närvänen A, Rytkönen-Nissinen M, Mäntyjärvi R, Vilja P, Virtanen T. Lipocalin allergen Bos d 2 is a weak immunogen. Int Immunol 14(4): 401-409, 2002.

Kinnunen T, Buhot C, Närvänen A, Rytkönen-Nissinen M, Saarelainen S, Pouvelle-Moratille S, Rautiainen J, Taivainen A, Mailleré B, Mäntyjärvi R, Virtanen T. The immunodominant epitope of lipocalin allergen Bos d 2 is suboptimal for human T cells. Eur J Immunol. 33:1717-1726, 2003.

Immonen A. Farci S. Taivainen A. Partanen J. Pouvelle-Moratille S. Narvanen A. Kinnunen T. Saarelainen S. Rytkonen-Nissinen M. Maillere B. Virtanen T. T Cell Epitope-Containing Peptides of the Major Dog Allergen Can f 1 as Candidates for Allergen Immunotherapy. J Immunol. 175(6):3614-20, 2005.

Kinnunen T. Kwok WW. Närvänen A. Rytkönen-Nissinen M. Immonen A. Saarelainen S. Taivainen A. Virtanen T. Immunomodulatory potential of heteroclitic analogs of the dominant T-cell epitope of lipocalin allergen Bos d 2 on specific T cells. Int. Immunol. 17(12):1573-8, 2005.

Immonen, AK., Taivainen, AH., Närvänen, ATO. Kinnunen, TT., Saarelainen, SA. Rytkönen-Nissinen MA., and Virtanen, TI. Use of multiple peptides containing T cell epitopes is a feasible approach for peptide-based immunotherapy in Can f 1 allergy. Immunology. 120(1): 38-46, 2007.

Kinnunen T. Jutila K. Kwok WW. Rytkönen-Nissinen M. Immonen A. Saarelainen S. Närvänen A. Taivainen A. Virtanen T. Potential of an altered peptide ligand of lipocalin allergen Bos d 2 for peptide immunotherapy. J. of Allergy and Clin. Immunol. 119(4):965-972, 2007.

Immonen A. Kinnunen T. Sirven P. Taivianen A. Houitte D. Peräsaari J. Närvänen A. Saarelainen S. Rytkönen-Nissinen M. Maillere B. Virtanen T. The major horse allergen Equ c 1 contains one immunodominant region of T cell epitopes. Clinical and Experimental Allergy 37: 939-947, 2007.

Saarelainen SA, Kinnunen TT, Buhot C, Närvänen AT, Kauppinen AK, Rytkönen-Nissinen MA, Maillere B, Virtanen TI. Immunotherapeutic potential of the immunodominant T-cell epitope of lipocalin allergen Bos d 2 and its analogues. Immunology. 123(3):358-66, 2008.

Updated: 7.01.2010MY