Pia Siljander

University of Helsinki, Helsinki, Uusimaa, Finland

Are you Pia Siljander?

Claim your profile

Publications (24)79.63 Total impact

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system. Keywords: extracellular vesicle; microvesicle; microparticle; exosome; physiology; prokaryote; eukaryote (Published: 14 May 2015) Citation: Journal of Extracellular Vesicles 2015, 4: 27066 - http://dx.doi.org/10.3402/jev.v4.27066
  • Source
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Motivation: Extracellular vesicles are spherical bilayered proteolipids, harboring various bioactive molecules. Due to the complexity of the vesicular nomenclatures and components, online searches for extracellular vesicle-related publications and vesicular components are currently challenging. Results: We present an improved version of EVpedia, a public database for extracellular vesicles research. This community web portal contains a database of publications and vesicular components, identification of orthologous vesicular components, bioinformatic tools, and a personalized function. EVpedia includes 6,879 publications, 172,080 vesicular components from 263 high-throughput datasets, and has been accessed >65,000 times from >750 cities. In addition, about 350 members from 73 international research groups have participated in developing EVpedia. This free web-based database might serve as a useful resource to stimulate the emerging field of extracellular vesicle research. Availability and implementation: The web site was implemented in PHP, Java, MySQL and Apache, and is freely available at http://evpedia.info.
    Bioinformatics 11/2014; DOI:10.1093/bioinformatics/btu741 · 4.62 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND Extracellular vesicles (EVs) are cell-derived membrane vesicles. EVs contain several RNAs such as mRNA, microRNAs, and ncRNAs, but less is known of their genomic DNA (gDNA) content. It is also unknown whether the DNA cargo is randomly sorted or if it is systematically packed into specific EV subpopulations. The aim of this study was to analyze whether different prostate cancer (PCa) cell-derived EV subpopulations (apoptotic bodies, microvesicles, and exosomes) carry different gDNA fragments. METHODS EV subpopulations were isolated from three PCa cell lines (LNCaP, PC-3, and RC92a/hTERT) and the plasma of PCa patients and healthy donors, and characterized by transmission electron microscopy, nanoparticle tracking analysis and total protein content. gDNA fragments of different genes were detected by real time quantitative PCR and confirmed by DNA sequencing. RESULTS We report that the concentration of EVs was higher in the cancer patients than in the healthy controls. EV subpopulations differed from each other in terms of total protein and DNA content. Analysis of gDNA fragments of MLH1, PTEN, and TP53 genes from the PCa cell-derived EV subpopulations showed that different EVs carried different gDNA content, which could even harbor specific mutations. Altogether, these results suggest that both nucleic acids and proteins are selectively and cell-dependently packed into the EV subtypes. CONCLUSIONS EVs derived from PCa cell lines and human plasma samples contain double-stranded gDNA fragments which could be used to detect specific mutations, making EVs potential biomarkers for cancer diagnostics and prognostics. Prostate © 2014 The Authors. The Prostate published by Wiley Periodicals, Inc.
    The Prostate 10/2014; 74(14). DOI:10.1002/pros.22853 · 3.57 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Introduction: Extracellular vesicles (EVs) have an important role in the intercellular transfer of genetic information. EVs have been shown to contain nucleic acids such as mRNA, microRNAs, ncRNAs and even DNA. However, less is known of the genomic DNA (gDNA) packed into EVs. It is also unknown, whether the gDNA cargo is randomly sorted to the different EV subpopulations, or if it is preferably packed into specific vesicle types. The aim of this study was to analyse whether different prostate cancer (PCa) cell-derived EV subpopulations (apoptotic bodies, microvesicles and exosomes) carry different gDNA fragments. Methods: EV subpopulations from 3 PCa cell lines (LNCaP, PC-3 and RC92a/h) were separated by differential ultracentrifugation (1,200�g, 20,000�g and 110,000�g). The different EV subpopulations were verified through transmission electron microscopy and characterized by total protein content and nanoparticle tracking analysis (NTA). gDNA fragments of different genes were detected by qPCR and confirmed by DNA sequencing. Results: We report that the PCa EV subpopulations were different in terms of total protein and DNA content. Although the particle concentration of microvesicles and exosomes by NTA were similar, the total protein content was significantly different. Particle concentration and total protein content correlated with each other for some, but not all PCa cell-derived microvesicles and exosomes. Analysis of the gDNA content of TP53, PTEN and MLH1 fragments in the EV populations from the different PCa cell lines showed, that different EV subpopulations carry different gDNA content, which could indicate a selective mechanism of nucleic acid packing depending on the cell and the EV subtype. Summary/conclusion: PCa EV subpopulations carry different gDNA sequences, which could potentially be used as diagnostic and prognostic biomarkers.
    Third International Meeting of ISEV 2014, Rotterdam, The Netherlands; 04/2014
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Mesenchymal stromal cells (MSC) are shown to have a great therapeutic potential in many immunological disorders. Currently the therapeutic effect of MSCs is considered to be mediated via paracrine interactions with immune cells. Umbilical cord blood is an attractive but still less studied source of MSCs. We investigated the production of extracellular membrane vesicles (MVs) from human umbilical cord blood derived MSCs (hUCBMSC) in the presence (MVstim) or absence (MVctrl) of inflammatory stimulus. hUCBMSCs were cultured in serum free media with or without IFN-γ and MVs were collected from conditioned media by ultracentrifugation. The protein content of MVs were analyzed by mass spectrometry. Hypoxia induced acute kidney injury rat model was used to analyze the in vivo therapeutic potential of MVs and T-cell proliferation and induction of regulatory T cells were analyzed by co-culture assays. Both MVstim and MVctrl showed similar T-cell modulation activity in vitro, but only MVctrls were able to protect rat kidneys from reperfusion injury in vivo. To clarify this difference in functionality we made a comparative mass spectrometric analysis of the MV protein contents. The IFN-γ stimulation induced dramatic changes in the protein content of the MVs. Complement factors (C3, C4A, C5) and lipid binding proteins (i.e apolipoproteins) were only found in the MVctrls, whereas the MVstim contained tetraspanins (CD9, CD63, CD81) and more complete proteasome complex accompanied with MHCI. We further discovered that differently produced MV pools contained specific Rab proteins suggesting that same cells, depending on external signals, produce vesicles originating from different intracellular locations. We demonstrate by both in vitro and in vivo models accompanied with a detailed analysis of molecular characteristics that inflammatory conditioning of MSCs influence on the protein content and functional properties of MVs revealing the complexity of the MSC paracrine regulation.
    12/2013; 2. DOI:10.3402/jev.v2i0.21927
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Extracellular vesicles (EVs) are membraneous vesicles released by a variety of cells into their microenvironment. Recent studies have elucidated the role of EVs in intercellular communication, pathogenesis, drug, vaccine and gene-vector delivery, and as possible reservoirs of biomarkers. These findings have generated immense interest, along with an exponential increase in molecular data pertaining to EVs. Here, we describe Vesiclepedia, a manually curated compendium of molecular data (lipid, RNA, and protein) identified in different classes of EVs from more than 300 independent studies published over the past several years. Even though databases are indispensable resources for the scientific community, recent studies have shown that more than 50% of the databases are not regularly updated. In addition, more than 20% of the database links are inactive. To prevent such database and link decay, we have initiated a continuous community annotation project with the active involvement of EV researchers. The EV research community can set a gold standard in data sharing with Vesiclepedia, which could evolve as a primary resource for the field.
    PLoS Biology 12/2012; 10(12):e1001450. DOI:10.1371/journal.pbio.1001450 · 11.77 Impact Factor
  • Pia R M Siljander
    [Show abstract] [Hide abstract]
    ABSTRACT: Platelet-derived microparticles (PMP) are a heterogeneous population of vesicles (< 1 mm) generated from the plasma membrane upon platelet activation by various stimuli. They are a discrete population differing from the exosomes which originate from the intracellular multivesicular bodies. PMP also differ from the microparticles derived from megakaryocytes despite the presence of several identical surface markers on the latter. The molecular properties and the functional roles of the PMP are beginning to be elucidated by the rapidly evolving research interest, but novel questions are simultaneously raised. This updated perspective discusses the most recent highlights in the PMP research in context with the methodological problems and the paradoxical role of the PMP in health and disease.
    Thrombosis Research 01/2011; 127 Suppl 2:S30-3. DOI:10.1016/S0049-3848(10)70152-3 · 2.43 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Collagen acts as a potent surface for platelet adhesion and thrombus formation under conditions of blood flow. Studies using collagen-derived triple-helical peptides have identified the GXX'GER motif as an adhesive ligand for platelet integrin alpha2beta1, and (GPO)(n) as a binding sequence for the signaling collagen receptor, glycoprotein VI (GPVI). The potency was investigated of triple-helical peptides, consisting of GXX'GER sequences within (GPO)(n) or (GPP)(n) motifs, to support flow-dependent thrombus formation. At a high-shear rate, immobilized peptides containing both the high-affinity alpha2beta1-binding motif GFOGER and the (GPO)(n) motif supported platelet aggregation and procoagulant activity, even in the absence of von Willebrand factor (VWF). With peptides containing only one of these motifs, co-immobilized VWF was needed for thrombus formation. The (GPO)(n) but not the (GPP)(n) sequence induced GPVI-dependent platelet aggregation and procoagulant activity. Peptides with intermediate affinity (GLSGER, GMOGER) or low-affinity (GASGER, GAOGER) alpha2beta1-binding motifs formed procoagulant thrombi only if both (GPO)(n) and VWF were present. At a low-shear rate, immobilized peptides with high- or low-affinity alpha2beta1-binding motifs mediated formation of thrombi with procoagulant platelets only in combination with (GPO)(n). Triple-helical peptides with specific receptor-binding motifs mimic the properties of native collagen I in thrombus formation by binding to both platelet collagen receptors. At a high-shear rate, either GPIb or high-affinity (but not low-affinity) GXX'GER mediates GPVI-dependent formation of procoagulant thrombi. By extension, high-affinity binding for alpha2beta1 can control the overall platelet-adhesive activity of native collagens.
    Journal of Thrombosis and Haemostasis 10/2008; 6(12):2132-42. DOI:10.1111/j.1538-7836.2008.03167.x · 5.55 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Collagen is a unique agonist of platelets, because it acts as an immobilized ligand that only causes platelet activation after stable adhesion. This review addresses the present understanding of how platelet interaction with collagen supports the process of thrombin generation and coagulation. Only some of the collagen-adhered platelets, that is, those showing profound changes in shape and shedding microparticles (resembling apoptotic cells), appear to contribute to the procoagulant activity of platelets. The main signaling receptor for collagen, glycoprotein VI, plays a key role in the platelet procoagulant response during thrombus formation; this is a reason why new anti-glycoprotein-VI antibodies are promising antithrombotic tools.
    Trends in Cardiovascular Medicine 05/2005; 15(3):86-92. DOI:10.1016/j.tcm.2005.03.003 · 2.07 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The purpose of this study was to determine if the results obtained in platelet function tests and whole blood perfusions are associated with those in platelet function analyser (PFA)-100. We used collagen type I monomers and fibrils to analyse the distinct roles of glycoprotein (GP) Ia/IIa and other collagen receptors in flowing blood under a high shear rate (1600/s) and in aggregation studies. Also, anticoagulation [citrate vs. D-phenylalanyl-1-prolyl-1 arginine chloromethyl ketone (PPACK)] was varied to enhance the functions of GP Ia/IIa, since it has been shown that the cation-poor environment of citrated blood impairs GP Ia/IIa-dependent platelet recruitment. Large interindividual variability (45-fold) was detected in deposition of platelets in whole blood perfusions over collagen monomers, whereas this variation was only fourfold in fibrils. In PFA, this variation was reduced to 2.5-fold. However, platelet deposition on monomers is associated with epinephrine-enhanced PFA (r=-.49, P<.03), whereas platelet deposition on fibrils is correlated with adenosine diphosphate (ADP)-enhanced PFA (r=-.47, P<.05), suggesting a distinct synergism between epinephrine and monomers (GP Ia/IIa) as well as ADP with fibrils (other collagen receptors). Donors with 807 C/C polymorphism of GP Ia (n=14) had longer lag phase in aggregation experiments compared with C/T (n=7) both by monomers and fibrils (P<.04), but these polymorphisms with their mild impact on GP Ia/IIa activity did not markedly differ in other tests. In conclusion, the results obtained in perfusion studies and PFA experiments correlated, but PFA fails to reveal the large-scale variability related to collagen-induced platelet responses.
    Thrombosis Research 08/2001; 103(2):123-33. DOI:10.1016/S0049-3848(01)00283-3 · 2.43 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In the final stages of activation, platelets express coagulation-promoting activity by 2 simultaneous processes: exposure of aminophospholipids, eg, phosphatidylserine (PS), at the platelet surface, and formation of membrane blebs, which may be shed as microvesicles. Contact with collagen triggers both processes via platelet glycoprotein VI (GPVI). Here, we studied the capacity of 2 GPVI ligands, collagen-related peptide (CRP) and the snake venom protein convulxin (CVX), to elicit the procoagulant platelet response. In platelets in suspension, either ligand induced full aggregation and high Ca(2+) signals but little microvesiculation or PS exposure. However, most of the platelets adhering to immobilized CRP or CVX had exposed PS and formed membrane blebs after a prolonged increase in cytosolic [Ca(2+)](i). Platelets adhering to fibrinogen responded similarly but only when exposed to soluble CRP or CVX. By scanning electron microscopic analysis, the bleb-forming platelets were detected as either round, spongelike structures with associated microparticles or as arrays of vesicular cell fragments. The phosphorylation of p38 mitogen-activated protein kinase (MAPK) elicited by CRP and CVX was enhanced in fibrinogen-adherent platelets compared with that in platelets in suspension. The p38 inhibitor SB203580 and the calpain protease inhibitor calpeptin reduced only the procoagulant bleb formation, having no effect on PS exposure. Inhibition of p38 also downregulated calpain activity. We conclude that the procoagulant response evoked by GPVI stimulation is potentiated by platelet adhesion. The sequential activation of p38 MAPK and calpain appears to regulate procoagulant membrane blebbing but not PS exposure.
    Arteriosclerosis Thrombosis and Vascular Biology 05/2001; 21(4):618-27. · 5.53 Impact Factor
  • Michael W. Hess, Pia Siljander
    [Show abstract] [Hide abstract]
    ABSTRACT: Visualisation of the procoagulant transformation of human platelets has recently become possible through use of an in vitro approach combined with fluorescence and phase contrast microscopy. Here, we extended these studies to the ultrastructural level by employing both rapid freezing/freeze-substitution and conventional ambient-temperature chemical fixation for transmission and scanning electron microscopy. Procoagulant transformation was only inducible by adhering platelets to collagen fibrils or to the collagen-related peptide and exposing them to physiological extracellular Ca2+ levels. Under these conditions prominent, 2- to 4-m-wide balloon-like structures were regularly observed, regardless of the specimen fixation protocol. In strong contrast to normal platelets in their vicinity, the balloons' subcellular architecture proved remarkably poor: dilute cytoplasm, no cytoskeleton, only a few, randomly distributed organelles and/or their remnants. Cryofixed balloons displayed intact and smooth surfaces whereas conventional specimen processing caused plasma membrane perforations and shrinkage of the balloons. Our results clearly show that neither the balloons themselves, nor their simple ultrastructure reflect fixation artefacts caused by inadequate membrane stabilisation. The balloons are interpreted as to be transformed and/or fragmented procoagulant platelets. Thus, the generation of balloons represents a genuine, final stage of platelet ontogenesis, presumably occurring alternatively to aggregate formation.
    Histochemie 04/2001; 115(5):439-443. DOI:10.1007/s004180100272 · 2.93 Impact Factor
  • Source
    S Ilveskero, P Siljander, R Lassila
    [Show abstract] [Hide abstract]
    ABSTRACT: In a new 2-stage assay of platelet procoagulant activity (PCA), we first subjected gel-filtered platelets to adhesion on collagen (as a model of primary hemostasis) or plasma clots (as a model of preformed thrombus) for 30 minutes, and then the adherent platelets were supplemented with pooled, reptilase-treated, diluted plasma. Defibrinated plasma provided coagulation factors for assembly on platelet membranes without uncontrolled binding of thrombin to fibrin(ogen). Platelet adhesion to both surfaces showed modest individual variation, which increased at platelet densities that allowed aggregation. However, adhesion-induced PCA varied individually and surface-independently >3-fold, suggesting a uniform platelet procoagulant mechanism. Permanently adhered platelets showed markedly enhanced PCA when compared with the platelet pool in suspension, even after strong activation. The rate of thrombin generation induced by clot-adherent platelets was markedly faster than on collagen-adherent platelets during the initial phase of coagulation, whereas collagen-induced PCA proceeded slowly, strongly promoted by tissue thromboplastin. Therefore at 10 minutes, after adjustment for adhered platelets, collagen supported soluble thrombin formation as much as 5 times that of the thrombin-retaining clots. Activation of platelets by their firm adhesion was accompanied by formation of microparticles, representing about one third of the total soluble PCA. Collagen-adhered platelets provide soluble thrombin and microparticles, whereas the preformed clot serves to localize and accelerate hemostasis at the injury site, with the contribution of retained thrombin and microparticles.
    Arteriosclerosis Thrombosis and Vascular Biology 04/2001; 21(4):628-35. DOI:10.1161/01.ATV.21.4.628 · 5.53 Impact Factor
  • Source
    Arteriosclerosis Thrombosis and Vascular Biology 04/2001; 21:618-627. DOI:10.1161/01.ATV.21.4.618 · 5.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Platelets in an advanced stage of activation change from coagulation-inactive to coagulation-promoting cells. This procoagulant response is characterised by exposure of aminophospholipids, such as phosphatidylserine, to the platelet surface and by formation of microvesicles. Under specific conditions, when both signalling and adhesive platelet receptors are occupied, collagen and also thrombin are able to trigger this response. Thus, platelets express high coagulation-promoting activity only after interacting with multiple receptors.
    Platelets 10/2000; 11(6):301-6. · 2.63 Impact Factor
  • Source
    P Siljander, R Lassila
    [Show abstract] [Hide abstract]
    ABSTRACT: The molecular differences between native-type collagen type I fibrils (NC) and their pepsinated monomers (PC) were used to uncover receptors involved in platelet-collagen interaction along the adhesion-activation axis. The platelet-depositing capacity of NC and PC under blood flow and their adhesive properties and respective morphologies, aggregation, procoagulant capacity, and tyrosine phosphorylation were compared under different cationic milieus, including or excluding the glycoprotein (GP) Ia/IIa. NC was consistently a more preferable and activating substrate than PC during flow (5 minutes) and in platelet aggregation. In PPACK-treated blood, both NC (3.3-fold) and PC (2.7-fold) increased platelet attachment on elevation of the shear rate from 500 to 1640 s(-1), whereas in citrated blood, adhesion and thrombus growth on PC were negligible under the high shear rate, unlike on NC (1.9-fold increase). The complete lack of platelet deposition on PC in citrated blood could be overcome by restoring physiological Mg(2+) concentration, and in contrast to NC, platelets interacting with PC were highly dependent on Mg(2+) during adhesion, aggregation, and procoagulant response. Monoclonal antibody (mAb 131.7) against GP IV inhibited platelet deposition to NC in citrated blood (2 minutes) by 49%, which was not further increased by coincubation with mAb against GP Ia (6F1). These results stress the importance of GP Ia/IIa in shear-resistant platelet deposition on collagen monomers. In native fibers, however, the preserved quaternary structure with telopeptides activates additional platelet receptors capable of substituting GP Ia/IIa and GP IV.
    Arteriosclerosis Thrombosis and Vascular Biology 01/2000; 19(12):3033-43. DOI:10.1161/01.ATV.19.12.3033 · 5.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Various collagen-based materials were used to assess the structural requirements of collagen for inducing the procoagulant response of adhering platelets, as well as the collagen receptors involved. Cross-linked or monomeric collagen-related peptide (CRP), Gly-Cys-Hyp-(Gly-Pro-Hyp)10-Gly-Cys-Hyp-Gly was highly adhesive for platelets in a glycoprotein VI-(GpVI-)dependent manner. Adhesion was followed by a prolonged increase in cytosolic [Ca2+]i, formation of membrane blebs, exposure of phosphatidylserine (PS) and generation of prothrombinase-stimulating activity. Fibrils of type-I collagen were less adhesive but, once adhered, many of the platelets presented a full procoagulant response. Monomeric type-I collagen was unable to support adhesion, unless Mg(2+)-dependent integrin alpha2beta1 interactions were facilitated by omission of Ca2+ ions. With all surfaces, however, post-addition of CaCl2 to adhering platelets resulted in a potent Ca(2+)-influx signal, followed by PS exposure and bleb formation. The procoagulant response elicited by binding to CRP was inhibited by anti-GpVI Fab fragments, but not by impeding integrin alpha2beta1-mediated events. With fibrillar collagen, it was inhibited by blocking either the GpVI- or integrin alpha2beta1-mediated interactions. This suggests that the triple-helical Gly-Pro-Hyp repeat in CRP and analogous sequences in fibrillar collagen stimulate the procoagulant response of adherent platelets by acting as ligands for GpVI. Influx of Ca2+ is required for this response, and adhesion via integrin alpha2beta1 serves to potentiate the signaling effects of GpVI.
    Thrombosis and Haemostasis 06/1999; 81(5):782-92. · 5.76 Impact Factor
  • P. Siljander, R. Lassila
    Atherosclerosis 10/1997; 134(1):196-196. DOI:10.1016/S0021-9150(97)89018-1 · 3.97 Impact Factor
  • Source
    P Siljander, O Carpen, R Lassila
    [Show abstract] [Hide abstract]
    ABSTRACT: Platelet-derived microparticles (MP) are reported to express both pro- and anticoagulant activities. Nevertheless, their functional significance has remained unresolved. The present study monitored the generation and fate of MP in an experimental model of thrombosis with costimulation of platelets by collagen and thrombin. When minimally anticoagulated (0.5 micromol/L PPACK) blood was perfused over immobilized fibrillar type I collagen in a flow chamber at a low shear rate (300 s(-1)), endogenous thrombin was generated, as evidenced by thrombin-antithrombin III complex. In contrast to full anticoagulation 150 micromol/L PPACK) and the absence of collagen, large platelet aggregates and fibrin ensued during perfusions over collagen in the presence of thrombin. In these thrombi, MP, defined as GPIIbIIIa- and P-selectin-positive vesicles (<1 micron), were found to align fibrin in immunofluorescence and scanning immunoelectron microscopy. Moreover, in sections of embolectomized thromboemboli from patients GPIIbIIIa- and P-selectin-positive material compatible with MP was detected in a fibrin strand-like pattern. In vitro binding studies showed that MP bound to fibrin and acted there as procoagulants. In summary, we show that MP generated during thrombus formation associate with local fibrin. This adhesive function fibrin could imply a sustained modulatory role for MP in evolving thrombi.
    Blood 07/1996; 87(11):4651-63. · 9.78 Impact Factor

Publication Stats

510 Citations
79.63 Total Impact Points

Institutions

  • 2000–2014
    • University of Helsinki
      • • Faculty of Pharmacy
      • • Department of Biosciences
      • • Department of Environmental Sciences
      • • Institute of Biotechnology
      Helsinki, Uusimaa, Finland
  • 2005
    • Maastricht University
      • Biochemie
      Maastricht, Provincie Limburg, Netherlands
  • 1996–2001
    • Wihuri Research Institute
      Helsinki, Southern Finland Province, Finland