Infektiot ja immuniteetti

Yksikön ryhmät tutkivat bakteerien, virusten ja elimistön puolustusjärjestelmän merkitystä terveydessä ja sairauksien synnyssä, sekä infektiotautien ja muiden tulehdustautien laboratoriodiagnostiikkaa ja hoitoa.

Yksikön johtaja

Tutkimusryhmät

Jukka Alinikula: Somatic hypermutation of antibody genes and beyond

Jukka Alinikula, University teacher

Contact: jukka.alinikula@utu.fi

Description of Research

We are interested in how efficient B-cell-mediated immunity is generated. Our focus is to understand how high-affinity antibody production is achieved. While cells generally keep somatic mutations at minimum to avoid genome instability and tumorigenesis, immunoglobulin genes during B cell development are actively mutated, e.g. through somatic hypermutation (SHM). Failure to correctly target the mutation machinery can have severe consequences for genome integrity and is involved in several forms of cancer, particularly lymphoma. We investigate the molecular mechanism of SHM targeting to immunoglobulin genes as well as the mechanisms that lead to mis-targeting of mutations to other sites in the genome, including proto-oncogenes.

Current topics

Targeting mechanism of SHM to immunoglobulin genes
Cancerous off-targeting of SHM to non-immunoglobulin genes

Research group members

PhD students: Anni Soikkeli
Other students: Alina Tarsalainen, Eveliina Honkonen

Recent key publications

Dinesh RK, Barnhill B, Ilanges A, Wu L, Daniel A, DA, Senigl F, Alinikula J, Shabanowitz J, Donald F. Hunt DJ, Schatz DG. Transcription factor binding at immunoglobulin enhancers is linked to somatic hypermutation targeting. European Journal of Immunology 50(3):380-95, 2020
Senigl F, Maman Y, Dinesh RK, Alinikula J, Seth RB, Pecnova L, Omer AD, Rao SSP, Weisz D, Buerstedde J-M, Lieberman Aiden E, Casellas R, Hejnar J, Schatz DG. Topologically Associated Domains Delineate Susceptibility to Somatic Hypermutation. Cell Reports. 29:3902-15, 2019
Budzyńska P, Kyläniemi M, Lassila O, Nera K-P and Alinikula J. BLIMP-1 is insufficient to induce antibody secretion in the absence of IRF4 in DT40 cells. Scandinavian Journal of Immunology 87(3), 2018
Budzyńska P, Kyläniemi M, Kallonen T, Soikkeli A, Nera K-P, Lassila O and Alinikula J. Bach2 regulates AID-mediated immunoglobulin gene conversion and somatic hypermutation in DT40 B cells. European Journal of Immunology. 47(6): 993-1001, 2017
Alinikula J & Schatz DG. Super-enhancer transcription converges on AID. Cell. 159:1490-1492, 2014

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Eeva-Liisa Eskelinen: Membrane dynamics in mammalian autophagy

Eeva-Liisa Eskelinen, Professor in Medical Cell Biology

Contact: eeva-liisa.eskelinen@utu.fi

Description of Research

Eskelinen group investigates membrane dynamics in mammalian autophagy, where cells transport redundant and damaged organelles to lysosomes for degradation and recycling. The cytoplasmic cargo is enveloped into an autophagosome that delivers the cargo for degradation and recycling by fusing with a lysosome. Autophagy is crucial for the homeostasis of most cells, in particular for postmitotic cells like neurons. In particular, the group is interested in the small GTPase RAB24. The group showed earlier that RAB24 is required for the clearance of autolysosomes in cells under basal conditions.

Eeva-Liisa Eskelinen also leads the Electron Microscopy Laboratory at the Institute of Biomedicine.

Current topics

* Molecular mechanisms of RAB24 in neuronal and hepatic cells
* Expression of RAB24 in tissues and cancer types

Research group members

* PhD students: Mauricio Ramm
* Postdocs: Martin Lopéz, Lav Tripathi
* Other students: Johannes Tapio, Hira Javed, Anson Antony

Key publications

Javed R, Jain A, Duque T, Hendrix E, Claude-Taupin A, Khan S, Jia J, Allers L, Timmins GS, Wang F, Lidke KA, Rusten TE, He Y, Reggiori FM, Eskelinen E-L, and Deretic V: Mammalian ATG8 proteins maintain autophagosomal membrane integrity through ESCRTs. EMBO J 2023, 42: e112845. DOI: 10.15252/embj.2022112845.
Kumar S, Javed R, Mudd M, Pallikkuth S, Lidke KA, Jain A, Tangavelou K, Gudmudsson SR, Ye C, Rusten T-E, Anonsen JH, Lystad AH, Claude-Taupin A, Anne Simonsen A, Salemi M, Phinney B, Li J, Guo L-W, Bradfute SB, Timmins G, Eskelinen E-L and Deretic V: Mammalian hybrid pre-autophagosomal structure HyPAS generates autophagosomes. Cell 2021,184:5950–5969. DOI: 10.1016/j.cell.2021.10.017
Ylä-Anttila P, Mikkonen E, Happonen KE, Holland P, Ueno T, Simonsen A, Eskelinen E-L: RAB24 facilitates clearance of autophagic compartments during basal conditions. Autophagy 2015, 11:1833-48. DOI: 10.1080/15548627.2015.1086522

Description of research

The overall goal of our research is to understand the differences and similarities between bacterial populations during carriage stage and disease with the focus on beta haemolytic streptococci. Beta haemolytic streptococci and especially group A (GAS, Streptococcus pyogenes) and group B (GBS, S. agalactiae) are important human pathogens with a broad range of disease types. Currently the research focus is on pregnant women, asymptomatic carriage of GAS and GBS during pregnancy and possible association of carriage with delivery complication. The overall health of mothers as well as newborns is investigated in association with bacterial carriage stage. Bacterial populations and microbiota during pregnancy are investigated with several molecular techniques.

Current topics

Carriage and household transmission of beta haemolytic streptococci during pregnancy
Microbiota composition at the time of delivery
National and local disease burden and aetiology of puerperal infections

Research group members

Doctoral researchers: recruitment pending
Technician: Ann-Sofie Wierda (part-time)

Recent key publications

Lönnqvist E, Gröndahl-Yli-Hannuksela K, Loimaranta V, Vuopio J. Low rate of asymptomatic carriage and salivary immunoglobulin A response to Group A Streptococci in the healthy adult population in Finland. In press 2022 Medical Microbiology and Immunology
Gröndahl-Yli-Hannuksela K, Beres SB, Hyyryläinen HL, Kallonen K, Musser JM and Vuopio J. Genetic evolution of invasive emm28 Streptococcus pyogenes strains and significant association with puerperal infections in young women, Finland. Clinical Microbiology and Infection 2020 Mar;27(3):420-427.
Vilhonen J, Vuopio J, Vahlberg T, Gröndahl-Yli-Hannuksela K, Rantakokko-Jalava K and Oksi J. Group A streptococcal bacteremias in Southwest Finland 2007-2018: epidemiology and role of infectious diseases consultation in antibiotic treatment selection. 2020. European Journal of Clinical Microbiology and Infectious Diseases, 2020 Jul;39(7):1339-1348.
Musser JM, Beres SB, Zhu L, Olsen RJ, Vuopio J, Hyyryläinen HL, Gröndahl-Yli- Hannuksela K, Kristinsson KG, Darenbergh J, Henriques-Normarki B, Hoffmann S, Caugant D, Smith AJ, Lindsayn D, Boragineo D, and Palzkill T. Reduced in vitro susceptibility of Streptococcus pyogenes to beta-lactam antibiotics associated with mutations in the pbp2x gene is geographically widespread. J. Clin. Microbiol. 2020, 25;58(4):e01993-19
Kachroo P, Eraso JM, Beres SB, Olsen RJ, Zhu L, Nasser W, Bernard PE, Cantu CC, Saavedra MO, Arredondo MJ, Strope B, Do H, Kumaraswami M, Vuopio J, Gröndahl-Yli-Hannuksela K, Kristinsson KG, Gottfredsson M, Pesonen M, Pensar J, Davenport ER, Clark AG, Corander J, Caugant DA, Gaini S, Magnussen MD, Kubiak SL, Nguyen HAT, Long SW, Porter AR, DeLeo FR, and Musser JM. Integrated Analysis of Population Genomics, Transcriptomics and Virulence Provides Novel Insights into Serotype M28 Streptococcus pyogenes Pathogenesis. Nature Genetics, 2019, Mar;51(3):548-559.

Description of Research

The research projects of this group focus on respiratory bacterial pathogens, host immunity and genetic susceptibility to infectious diseases. We study 1) cell-mediated and humoral immune responses after acellular pertussis vaccines and natural infections; 2) impact of innate immune gene polymorphisms on nasopharyngeal bacterial colonization, respiratory infections and asthma development in children; 3) molecular surveillance of Bordetella pertussis and Corynebacterium diphtheria; and 4) Development of novel point of care tests for bacterial infections including pertussis. The research group has been leading several EU-funded projects since 2005 and serves as Finnish national reference laboratory for pertussis and diphtheria.

Current topics

Impact of acellular pertussis (aP) vaccination in pregnancy on vaccine responses in infants who receive aP vaccine subsequently
Functional antibodies induced after aP vaccination across age-groups
Genomic changes of Bordetella pertussis and its impact on vaccine effectiveness in Europe
Innate immune gene polymorphisms on nasopharyngeal bacterial colonization, respiratory infections and asthma development in children

Research group members

Senior researchers: Jussi Mertsola, Lauri Ivaska
PhD students: Alex-Mikael Barkoff, Johanna Teräsjärvi, Aapo Knuutila, Elina Tenhu, Niina Forsten
Technicians: Elisa Laakso, Kaisu Kaistinen, Tuula Rantasalo (part time)

Recent key publications

Knuutila A, Dalby T, Barkoff AM, Jørgensen CS, Fuursted K, Mertsola J, Markey M, He Q. Differences in epitope-specific antibodies to pertussis toxin after infection and acellular vaccinations. Clin Transl Immunology 2020; 9: e1161.
Zhang J, Chen N, Chen Z, Liu Y, Zheng K, Qiu Y, Zhang N, Zhu J, Yu H, He Q. Low plasma mannose binding lectin, but not L-ficolin is associated with spontaneous clearance of hepatitis C virus after infection. Front Immunol 2020;11:587669.
Barkoff AM, Mertsola J, Pierard D, Dalby T, Hoegh SV, Guillot S, Stefanelli P, van Gent M, Berbers G, Vestrheim D, Greve-Isdahl M, Wehlin L, Ljungman M, Fry NK, Markey K, He Q. Pertactin-deficient Bordetella pertussis isolates: evidence of increased circulation in Europe. Euro Surveill 2019;24(7):pii=1700832.
Zhu J, Chen N, Zhou S, Zheng K, Sun L, Zhang Y, Cao L, Zhang X, Xiang Q, Chen Z, Wang C, Fan C, He Q. Severity of enterovirus A71 infection in a human SCARB2 knock-in mouse model is dependent on infectious strain and route. Emerg Microbe Infect 2018;7:205.
Barkoff AM, Mertsola J, Pierard D, Dalby T, Hoegh SV, Guillot S, Stefanelli P, van Gent M, Vestrheim D, Greve-Isdahl M, Wehlin L, Ljungman M, Fry NK, Auranen K, He Q. Surveillance of Circulating Bordetella pertussis strains in Europe during 1998-2015. J Clin Microbiol 2018 Apr 25;56(5). pii: e01998-17.

Description of Research

Overcoming tumor-related immunosuppression presents a significant obstacle to successful cancer treatment. To activate the host’s anti-tumor immunity, our research exploits macrophage reprogramming as an alternative approach to stimulate CD8 T-cell mediated tumor cell killing.

Current topics

Mechanisms regulating macrophage function in the tumor microenvironment
Macrophage-derived extracellular vesicles in the regulation of T-cell activation
Macrophage targeted immunotherapy

Research group members

PhD students: Miro Viitala, Jenna Rannikko, Sina Tadayon
Other students: Nesrin Mohamed
Technicians: Mari Parsama

Recent key publications

Viitala M, Virtakoivu R, Tadayon S, Rannikko J, Jalkanen S, Hollmén M. Immunotherapeutic. Blockage of Macrophage Clever-1 Reactivates the CD8+ T Cell Response Against Immunosuppressive Tumors. Clin Can Res 2019, 25:3289-3303.
Hollmén M, Karaman S, Schwager S, Lisibach A, Christiansen AJ, Maksimow M, Varga Z, Jalkanen S, Detmar M. G-CSF regulates macrophage phenotype and associates with poor overall survival in human triple-negative breast cancer. Oncoimmunology 2015, 5: e1115177.
Hollmén M, Roudnicky F, Karaman S, Detmar M. Characterization of macrophage - cancer cell crosstalk in estrogen receptor positive and triple-negative breast cancer. Scientific Reports 2015, 5:9188.
Takeda A, Hollmén M, Dermadi D, Pan J, Francis Brulois K, Kaukonen R, Lönnberg T, Boström P, Koskivuo I, Irjala H, Miyasaka M, Salmi M, Butcher EC, Jalkanen S. Single-cell survey of human lymphatics unveils marked endothelial cell heterogeneity and mechanisms of homing for neutrophils. Immunity 2019, pii: S1074-7613(19)30297-3.
Tadayon S, Dunkel J,Takeda A, Halle O, Karikoski M, Gerke H, Rantakari P, Virtakoivu R, Pabst O, Salmi M, Hollmén M *, Jalkanen S*. Clever-1 contributes to lymphocyte entry into the spleen via the red pulp. Science Immunology 2019 Vol. 4, Issue 33, eaat0297. *equal contribution

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Veijo Hukkanen: Herpesviruses as friends and enemies

Veijo Hukkanen

Pentti Huovinen: Human microbiota

Pentti Huovinen

Jukka Hytönen: Lyme borreliosis: a comprehensive approach

Jukka Hytönen, Associate professor of bacteriology

Contact: jukka.hytonen@utu.fi

Description of Research

Our project focuses on Lyme borreliosis (LB) and other tick-borne infections and addresses the following questions: Pathogenesis of LB and the role of borrelia adhesins in the process. Molecular and cellular events in the pathogenesis of Lyme neuroborreliosis. Development of novel diagnostic tools for LB. Development of PET/CT imaging of LB. Antibiotic treatment of LB. Prevalence of ticks and tick-borne pathogens in Finland. Epidemiology of LB and other tick-borne infections in Finland.

Current topics

Identification of novel biomarkers of LB using metabolomics profiling of LB patient samples
scRNA-sequenceing of mouse and LB patient samples to better understand the immunopathology of LB and to identify novel markers of LB
Development of new methods for LB serology
Development of immuno-PET tracers for PET/CT imaging of LB

Research group members

Senior researchers: Annukka Pietikäinen, Eeva Feuth
PhD students: Otto Glader, Elisa Kortela, Maija Laaksonen, Meri Rouhiainen
Technicians: Tuula Rantasalo

Recent key publications

Kortela E., Kanerva M., Puustinen J., Hurme S., Airas L., Lauhio A., Hohenthal U., Jalava-Karvinen P., Nieminen T., Finnilä T., Häggblom T., Marttila-Vaara M., Pietikäinen A., Koivisto M. Vilhonen J., *Hytönen J., *Oksi J.: Oral doxycycline compared to intravenous ceftriaxone for the treatment of Lyme neuroborreliosis: a multicentre, equivalence, randomised, open-label trial. Clinical Infectious Diseases (2020) Mar 5. pii: ciaa217. doi: 10.1093/cid/ciaa217. * Equal contribution
Cuellar J., Dub T., *Sane J., *Hytönen J.: Seroprevalence of Lyme borreliosis in Finland 50 years ago. Clinical Microbiology and Infection (2019) Oct 14. pii: S1198-743X(19)30530-0. doi: 10.1016/j.cmi.2019.10.003. * Equal contribution
Glader O., Puljula E., Jokioja J., Karonen M., Sinkkonen J., Hytönen J.: NMR metabolome of Borrelia burgdorferi in vitro and in vivo in mice. Scientific reports (2019) 9:8049 | https://doi.org/10.1038/s41598-019-44540-5.
Cuellar J., Pietikäinen A., Glader O., Liljenbäck H., Söderström M., Hurme S., Salo J. Hytönen J.: Borrelia burgdorferi infection in biglycan knock-out mice. Journal of Infectious Diseases (2019) Jun 5;220(1):116-126. doi: 10.1093/infdis/jiz050.
Sajanti E., Virtanen M., Helve O., Kuusi M., Lyytikäinen O., *Hytönen J., *Sane J.: Lyme borreliosis in Finland, 1995–2014. Emerging Infectious Diseases (2017), Vol. 23, No. 8. * Equal contribution

Description of Research

The overall goal of our research is to elucidate the mechanisms regulating the traffic of leukocytes and cancer cells in the body. Harmful leukocyte migration into the joints in rheumatoid arthritis and into the pancreas in diabetes are examples of diseases where leukocytes cause extensive destruction. These inflammatory diseases can be cured by inhibiting leukocyte trafficking. Also, metastasising malignant cells often use the same mechanisms as leukocytes when extravasating from blood to different organs or migrating via the lymphatics into distant sites. The results obtained can be utilized when new types of drugs are developed to treat harmful inflammations and cancer.

Current topics

In cancer: How cancer modifies lymphatics for promoting its spread
In inflammation: Does the polymorphism in interferon-beta receptor affect the outcome of viral infections

Research group members

Senior researchers: Gennady Yegutkin; Imtiaz Iftakhar-e-Khuda; Dominik Eichin
PhD students: Karolina Losenkova, Sina Tadayon, Riikka Siitonen
Other students: Leo Karvinen
Technicians: Riikka Sjöroos, Sari Mäki, Maritta Pohjansalo, Teija Kanasuo

Recent key publications

Iftakhar-E-Khuda I, Fair-Mäkelä R, Kukkonen-Macchi A, Elima K, Karikoski M, Rantakari P, Miyasaka M, Salmi M, Jalkanen S. Gene-expression profiling of different arms of lymphatic vasculature identifies candidates for manipulation of cell traffic. PNAS 113:10643-10648, 2016.
Tadayon S, Dunkel J, Takeda A, Halle O, Karikoski M, Gerke H, Rantakari P, Virtakoivu R, Pabst O, Salmi M, Hollmén M*, Jalkanen S*. Clever-1 contributes to lymphocyte entry into the spleen via the red pulp. Science Immunol 4: 33. 2019. (*shared)
Takeda A, Hollmén M, Dermadi D, Pan J, Brulois KF, Kaukonen R, Lönnberg T, Boström P, Koskivuo I, Irjala H, Miyasaka M, Salmi M, Butcher EC, Jalkanen S. Single-cell survey of human lymphatics unveils unexpected heterogeneity and mechanisms of homing for neutrophils. Immunity 51:561-572, 2019.
Jalkanen J*, Pettilä V*, Huttunen T, Hollmen M*, Jalkanen S*. Glucocorticoids Inhibit Type I IFN Beta Signaling and the Upregulation of CD73 in Human Lung. Intensive Care Med 46:1937-1940, 2020. (*shared)
Jalkanen S, Salmi M. Lymphatic endothelial cells of the lymph node. Nature Rev Immunol 20:566-578, 2020.

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Ilkka Julkunen: Innate and adaptive immunity in viral infections

Ilkka Julkunen

Laura Kakkola: Emerging pathogens

Laura Kakkola, PhD, Adjunct Professor in Virology, Laboratory Manager, Biosafety Officer

Contact: laura.kakkola@utu.fi

Description of Research

Our research focuses to understand what are the key molecular changes required in the zoonotic viruses for the crossing of species barriers (i.e. spillover) and the changes that enable the virus to replicate in humans and spread in the human population. We are interested in virus-host interactions, how viruses interfere with immune responses, and could these events be utilized in vaccine, antiviral drug or diagnostic test development.

Current topics

Crossing species barriers - molecular mechanisms of infectious disease emergence.
Innate immune responses in virus infections.

Research group members

Senior researchers: Eda Altan Taracki and with Professor Ilkka Julkunen: Pekka Kolehmainen
PhD students: Hira Khan and with Professor Ilkka Julkunen: Arttu Reinholm, Milja Belik, Pinja Jalkanen, Rickard Lundberg
Technicians: Sari Maljanen

Recent key publications

Belik M, Jalkanen P, Lundberg R, Reinholm A, Laine L, Väisänen E, Skön M, Tähtinen P, Ivaska L, Pakkanen S, Häkkinen H, Ortamo E, Pasternack A, Ritvos M, Naves R, Miettinen S, Sironen T, Vapalahti O, Ritvos O, Österlund P, Kantele A, Lempainen J, Kakkola L, Kolehmainen P, and Julkunen I. Comparative analysis of COVID-19 vaccine responses and third booster dose-induced neutralizing antibodies against Delta and Omicron variants. Nature Communications, 2022,13(1):2476. doi: 10.1038/s41467-022-30162-5
Hurme A, Jalkanen P, Heroum J, Liedes O, Vara S, Melin M, Teräsjärvi J, He Q, Pöysti S, Hänninen A, Oksi J, Vuorinen T, Kantele A, Tähtinen PA, Ivaska L, Kakkola L, Lempainen J, Julkunen I. Long-lasting T cell responses in BNT162b2 COVID-19 mRNA vaccinees and COVID-19 convalescent patients. Frontiers in Immunology, 2022, 13:869990. doi: 10.3389/fimmu.2022.869990
He FB, Khan H, Huttunen M, Kolehmainen PJ, Melen K, Maljanen S, Qu M, Jiang M, Kakkola L, Julkunen I. Filovirus VP24 proteins differentially regulate RIG-I and MDA5-dependent type I and III interferon promoter activation. Frontiers of Immunology, 2022, 12:694105. doi: 10.3389/fimmu.2021.694105
Jalkanen P, Kolehmainen P, Häkkinen HK, Huttunen M, Tähtinen PA, Lundberg R, Maljanen S, Reinholm A, Tauriainen S, Pakkanen SH, Levonen I, Nousiainen A, Miller T, Välimaa H, Ivaska L, Pasternack A, Naves R, Ritvos O, Österlund P, Kuivanen S, Smura T, Hepojoki J, Vapalahti O, Lempainen J, Kakkola L, Kantele A, Julkunen I. COVID-19 mRNA vaccine induced antibody responses against three SARS-CoV-2 variants. Nature Communications, 2021, 12(1):3991. doi:10.1038/s41467-021-24285-4 Joint supervision LK, AK, IJ
Jalkanen P, Pasternack A, Maljanen S, Melén K, Kolehmainen P, Huttunen M, Lundberg R, Tripathi L, Khan H, Ritvos MA, Naves R, Haveri A, Österlund P, Kuivanen S, Jääskeläinen AJ, Kurkela S, Lappalainen M, Rantasärkkä K, Vuorinen T, Hytönen J, Waris M, Tauriainen S, Ritvos O, Kakkola L, Julkunen I. A Combination of N and S Antigens With IgA and IgG Measurement Strengthens the Accuracy of SARS-CoV-2 Serodiagnostics. J Infect Dis. 2021, 224(2):218-228. doi:10.1093/infdis/jiab222OR, LK, IJ contributed equally

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Johanna Lempainen: Immunogenetics of autoimmune diseases

Johanna Lempainen, MD, Adjunct Professor, Pediatrician

Contact: johanna.lempainen@utu.fi

Description of Research

Our research focuses on the pathogenesis of type 1 diabetes. In particular, we investigate the genetic background of T1D, risk gene effects on various disease phases, and heterogeneity of the disease pathogenesis. We mainly perform genetic analyses, but also search for alterations in gene regulation and immune activation leading to autoimmunity. We aim to combine genetic and environmental data during the autoimmunity to identify interactions and disease pathway specific effects.

Current topics

Genetics of type 1 diabetes
Heterogeneity of type 1 diabetes pathogenesis
Immune alterations in early childhood

Research group members

Senior researchers: Antti-Pekka Laine, Minna Kiviniemi, Jorma Ilonen
PhD students: Mari-Liis Mikk, Milla Valta, Sirpa Pahkuri
Technicians: Mia-Maria Karlsson, Terhi Laakso, Piia Nurmi, Anne Suominen

Recent key publications

Ilonen J, Lempainen J, Hammais A, Laine A-P, Härkönen T, Toppari J, Veijola R, Knip M, the Finnish Pediatric Diabetes Register. Primary islet autoantibody at initial seroconversion and autoantibodies at diagnosis of type 1 diabetes as markers of disease heterogeneity. Pediatr Diabetes 2018;19(2):284-292
Bauer W, Veijola R, Lempainen J, Kiviniemi M, Härkönen T, Toppari J, Knip M, Gyenesei A, Ilonen J. Age at seroconversion, HLA genotype and specificity of autoantibodies in progression of islet autoimmunity in childhood. J Clin Endocrinol Metab 2019;104:4521-4530
Ilonen J, Lempainen J, Veijola R. The heterogeneous pathogenesis of type 1 diabetes mellitus. Nat Rev Endocrinol 2019 15(11):635-650
Valta M, Gazali AM, Viisanen T, Ihantola EL, Ekman I, Toppari J, Knip M, Veijola R, Ilonen J, Lempainen J, Kinnunen T. Type 1 diabetes linked PTPN22 gene polymorphism is associated with the frequency of circulating regulatory T cells. Eur J Immunol 2020;50(4):581-588
Mikk ML, Pfeiffer S, Kiviniemi M, Laine AP, Lempainen J, Härkönen T, Toppari J, Veijola R, Knip M, Ilonen J; Finnish Pediatric Diabetes Register. HLA-DR-DQ haplotypes and specificity of the initial autoantibody in islet specific autoimmunity. Pediatr Diabetes, Online ahead of print

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Pieta Mattila: Cytoskeleton in lymphocyte activation

Pieta Mattila, Adjunct Professor, Academy Research Fellow

Contact: Pieta.mattila@utu.fi

Description of Research

Our group focuses on the mechanisms of early B cell activation. Upon activation by various pathogens, B cells mount highly specific antibody responses as well as immunological memory. We are particularly interested in the regulation of the critical B cell antigen receptor (BCR) signaling and the immediate cellular responses to antigenic trigger, which involve formation of an immunological synapse and antigen uptake and processing for further presentation to T cells. We use single-cell genomics with single-cell proteomics combined with various sophisticated in vivo mouse models to answer our research question. Our research aims for better understanding of the adaptive immune responses both in health and disease, and to facilitate more efficient harnessing of lymphocytes in the immunological therapies of the future.

Current topics

BCR signaling: principles and cross-talk with other receptors.
B cell antigen processing.
Novel proteomic approaches to reveal the protein players involved in early B cell activation and B cell immunological synapse formation.

Research group members

Senior researchers: Petar Petrov
PhD students: Alexey Sarapulov, Luqman Awoniyi, Marika Runsala (Vainio), Sara Hernández-Pérez
Other students: Diogo Cunha, Eveliina Uski
Technicians: Laura Grönfors

Recent key publications

Sarapulov AV, Petrov P, Hernández-Pérez S, Šuštar V, Kuokkanen E, Cords L, Samuel RVM, Vainio M, Fritzsche M, Carrasco YR, and Mattila PK. (2020) Missing-In-Metastasis / Metastasis Suppressor 1 modulates B cell receptor signaling, B cell metabolic potential and T cell-independent immune responses. Frontiers in Immunology. 11:599.
Hernández-Pérez S, Vainio M, Kuokkanen E, Sustar V, Petrov P, Fórsten S, Paavola V, Rajala J, Awoniyi LO, Sarapulov AV, Vihinen H, Jokitalo E, Bruckbauer A, and Mattila PK. (2019) B cells rapidly target antigen and surface-derived MHCII into peripheral degradative compartments. Journal of Cell Science; 133:jcs235192
Burbage M, Keppler SJ, Montaner B, Mattila PK*, Batista FD. (2017) The Small Rho GTPase TC10 Modulates B Cell Immune Responses. Journal of Immunology, 199:1682-1695. *corresponding author
Mattila PK, Batista FD and Treanor, B (2016) Dynamics of the actin cytoskeleton mediates receptor cross talk: An emerging concept in tuning receptor signaling. Journal of Cell Biology; 212:267-80.
Mattila PK, Feest C, Depoil D, Treanor B, Montaner B, Otipoby KL, Carter R, Justement LB, Bruckbauer A, Batista FD. (2013) The actin and tetraspanin networks organize receptor nanoclusters to regulate B cell receptor-mediated signaling. Immunity; 38:461-74.

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Alexander Mildner: Monocyte and macrophage function during health and disease

Alexander Mildner, Associate Professor

Contact: Alexander.mildner@utu.fi

Description of Research

Tissue resident macrophages are long-lived cells that are distributed throughout the body and migrate into the tissue during embryogenesis. They are specialized in ingesting and processing dead cells, debris and foreign materials, and in the recruitment of other immune cells – like monocytes – to sites of injury in response to inflammatory signals. Monocytes, on the other hand, represent short-lived cells that can be found in the peripheral circulation. Traditionally, it was assumed that monocytes represent an intermediate stage, linking mononuclear phagocyte precursors in the bone marrow with terminally differentiated tissue resident macrophages. However, this concept seems to hold true only for certain tissues. In most of the cases, embryo-derived tissue macrophages are endowed with an intrinsic self-renewal program to maintain homeostasis, while monocyte descendants are devoid of this capacity. Instead, monocytes are highly plastic cells and can differentiate – depending on the cellular context – into various cell types with fundamental different functions like effector monocytes, monocyte-derived dendritic cells and monocyte-derived macrophages.

The transcription factor C/EBPβ is expressed in cells of the myeloid lineage, especially in monocytes, macrophages and dendritic cells. Recently, we applied epigenetic approaches to identify C/EBPβ as one of the main regulators of monocyte and Alveolar macrophage development under physiological conditions. Deficiency of C/EBPβ in mice let to a complete absence of Ly6C- monocytes due to impaired induction of the monocytic survival factor Nr4a1. In Alveolar macrophages, C/EBPβ controlled the expression of a lipid catabolic program.

We are currently investigating the differentiation of myeloid cells under steady state as well as pathological conditions such as autoimmunity in various tissues using epigenetic approaches including ATACseq, ChIPseq and high resolution immune profiling like scRNA-Seq. The central goal of our laboratory is to identify new factors that are involved in the differentiation of monocytes and macrophages under pathological conditions. We hope to manipulate the fate and activation status of macrophages and thereby beneficially influence disease progression.

Current topics

Monocytes differentiation and function during neuroinflammation
Microglia heterogeneity
Tissue-specific function of macrophages

Research group members

PhD students: Besmir Hyseni, Ae Parena
PostDoc: Luis Crisostomo

Recent publications

Lyras EM, Zimmermann K, Wagner LK, Dörr D, Klose CSN, Fischer C, Jung S, Yona S, Hovav AH, Stenzel W, Dommerich S, Conrad T, Leutz A, Mildner A. Tongue immune compartment analysis reveals spatial macrophage heterogeneity. Elife. 2022 Jun 24;11:e77490. doi: 10.7554/eLife.77490. https://pubmed.ncbi.nlm.nih.gov/35749158/
Giladi A*, Wagner LK*, Li H, Dörr D, Medaglia C, Paul F, Shemer A, Jung S, Yona S, Mack M, Leutz A, Amit I*, Mildner A* (2020): Cxcl10+ monocytes define a pathogenic subset in the central nervous system during autoimmune neuroinflammation. Nat Immunol. 21(5):525-534. https://pubmed.ncbi.nlm.nih.gov/32313246/
Guilliams M*, Mildner A*, Yona S* (2018): Developmental and Functional Heterogeneity of Monocytes. Immunity. 16;49(4):595-613. https://pubmed.ncbi.nlm.nih.gov/30332628/
Mildner A*, Schönheit J*, Giladi A, David E, Lara-Astiaso D, Lorenzo-Vivas E, Paul F, Chappell-Maor L, Priller J, Leutz A, Amit I, Jung S (2017): Genomic Characterization of Murine Monocytes Reveals C/EBPβ Transcription Factor Dependence of Ly6C- Cells. Immunity. 46(5):849-862.e7. https://pubmed.ncbi.nlm.nih.gov/28514690/

Links

Utu research profile

Orcid profile

Researchgate

Cecilia Naucler: Immunometabolism

Cecilia Söderberg-Nauclér MD, PhD, Professor of Immunology

Contact: cecilia.naucler@utu.fi

Description of the research

I have a long-standing interest in pathogenesis studies of human cytomegalovirus (HCMV). This virus is considered harmless for healthy individuals but may cause severe disease in immunocompromised patients such as organ and stem cell transplant patients and AIDS patients. It is also the most common congenital infection and may cause birth defects, of which the most common are hearing loss and mental retardation. Emerging evidence also imply a role of this virus in inflammatory diseases and cancer.

HCMV establishes a latent/persistent life-long infection after a primary infection. 70-90% of adults have been infected with and are carriers of this virus. The virus resides in a latent state mainly in myeloid lineage cells in the bone marrow and reactivation occurs when these cells differentiate into inflammatory macrophages or dendritic cells in various tissues. Infected cells further promote inflammation via enhanced expression of 5-LO and COX-2 and induced production of inflammatory cytokines and chemokines. HCMV is often found to be activated in inflamed tissue specimens obtained from patients with inflammatory diseases such as SLE, rheumatoid arthritis, inflammatory bowel disease, cardiovascular diseases and aortic aneurysms, while rarely detected in healthy tissues. Thereby, there is a close relationship between this virus and inflammation, but it is today unclear how important HCMV is in promoting clinical disease activity and progression of these diseases.

HCMV is also commonly found to be active in tumors of different origin; HCMV proteins and nucleic acids are found in >90% of glioblastoma, neuroblastoma, medulloblastoma, breast, colon, prostate and ovarian cancer. Both primary tumors as well as metastases are virus positive, while healthy tissues surrounding tumors and metastases are virus negative. New evidence imply that perhaps only certain HCMV strains may be associated with cancer, and hence potentially be oncogenic. We are currently studying the effect of anti-HCMV therapy in glioblastoma patients in a randomized trial, VIGAS2. Retrospective analyses of so far treated patients (139 patients) indicate substantial prolonged survival time in patients receiving anti-viral therapy. These observations imply a potential role of this virus in cancer.

Activation of immune cells depend on alterations in cellular metabolism; i.e the Warburg effect, which is also essential for cancer cells to grow. Although the metabolic alterations to the Warburg effect is essential for inflammation and cancer, it is not known how cells switch from normal metabolism to the Warburg effect. HCMV establishes the Warburg effect in infected cells, which appears to be essential for reactivation of latent HCMV and virus production. We have used HCMV as a tool to try to understand the underlying mechanisms of the Warburg effect in immune cells and cancer cells. We made unexpected insights into how cells with a normal metabolism switch to the Warburg effect, which allowed us to identify metabolic inhibitors that we are now testing how they affect immune cell activation and cancer cell growth.

The long-term goal of our projects is to further understand how cellular metabolism control immune activation, cancer cell growth, and the life cycle of HCMV that appears to be closely involved in these diseases. We hope that this will allow us to find new treatment strategies for many of our common diseases. Our research is carried out at Turku University and Karolinska Institutet.

Current topics

Defining key common metabolic mechanisms governing macrophage differentiation, T cell activation and cancer cell growth; i.e the underlying mechanism of the Warburg effect
Defining how metabolic alterations change cellular fate and induce HCMV reactivation via epigenetic mechanisms
Defining genetic variants that affect immune functions and confer immune control of viral and bacterial infections
To assess whether anti-viral therapy to HCMV can improve the prognosis for glioblastoma patients (clinical multicentral randomized clinical trial, VIGAS2, 220 patients)

Research group members

University of Turku:

PhD students: Hatem Abou-Guendia, Iqra Anam Khwaja, Mohammed Pirouzfar, Shaghayegh Hansanpour
Post doc: Päivi Ylä-Anttila

Karolinska Institutet:

PhD students : Mattia Russel Pantalone, Xinling Xu, Inti Peredo Harvey, Nerea Martin Almazan
Post docs: Jennifer Gorwood, Kristen Schroeder, Tong Liu, Koon Chu Yaiw
Associate professors: Afsar Rahbar, Piotr Religa
Senior researcher: Giuseppe Stragliotto, neurooncologist
Medical student: Cedric Bratt

Recent key publications

Cell Death and Differentiation

Joanna Maria Merchut-Maya, Jiri Bartek Jr., Jirina Bartkova, Mattia Russel Pantalone, Panagiotis Galanos, MyungHee Lee, Huanhuan L. Cui, Afsar Rahbar, Patrick J. Shilling, Christian Beltoft Brøchner, Helle Broholm, Apolinar Maya-Mendoza, Cecilia Söderberg-Naucler* and Jiri Bartek*Cytomegalovirus hijacks host stress response fueling genome instability *Shared senior authorship, 2022 Feb 22. doi: 10.1038/s41418-022-00953-w.

EbioMedicine

Söderberg-Nauclér C New mechanistic insights of the pathogenicity of high-risk cytomegalovirus (CMV) strains derived from breast cancer: Hope for new cancer therapy options. 2022 Jun 13;81:104103. doi: 10.1016/j.ebiom.2022.104103.

Cancers

Peredo-Harvey I, Rahbar A, Söderberg-Nauclér C. Presence of the human Cytomegalovirus in Glioblastomas- a Systematic Review 2021 Oct 9;13(20):5051. doi: 10.3390/cancers13205051.PMID: 34680198

Clinical Cancer Research

Stragliotto G, Pantalone MR, Rahbar A, Bartek J, Söderberg-Naucler C. Valganciclovir as add-on to standard therapy in glioblastoma patients. 2020. Clin Cancer Res. 2020 Aug 1;26(15):4031-4039.

Lancet

King C, Einhorn L, Brusselaers N, Carlsson M, Einhorn S, Elgh F, Frisén J, Gustafsson Å, Hanson S, Hanson C, Hedner T, Isaksson O, Jansson A, Lundkvist Å, Lötvall J, Lundback B, Olsen B, Söderberg-Nauclér C, Wahlin A, Steineck G, Vahlne A. COVID-19-a very visible pandemic. 2020 Aug 8;396(10248):e15.

Journal of Cancer Research and Clinical Oncology

Costa H, Touma J, Davoudi B, Benard M, Sauer T, Geisler J, Vetvik K, Rahbar A, Söderberg-Naucler C. Human cytomegalovirus infection is correlated with enhanced cyclooxygenase-2 and 5-lipoxygenase protein expression in breast cancer. 2019;145(8):2083-95.

Translational Oncology

Radestad AF, Estekizadeh A, Cui HL, Kostopoulou ON, Davoudi B, Hirschberg AL, Carlson J, Rahbar A, Söderberg-Naucler C. Impact of Human Cytomegalovirus Infection and its Immune Response on Survival of Patients with Ovarian Cancer. 2018;11(6):1292-300.

Cell Reports

Low H, Mukhamedova N, Cui HL, McSharry BP, Avdic S, Hoang A, Ditiatkovski M, Liu Y, Fu Y, Meikle PJ, Blomberg M, Polyzos KA, Miller WE, Religa P, Bukrinsky M, Söderberg-Naucler C, Slobedman B, Sviridov D. Cytomegalovirus Restructures Lipid Rafts via a US28/CDC42-Mediated Pathway, Enhancing Cholesterol Efflux from Host Cells. 2016;16(1):186-200.

Cell Host Microbe

Söderberg-Naucler C. CMV and NK Cells: An Unhealthy Tryst? 2016;19(3):277-9.

Cell Death Differentiation

Fornara O, Bartek J, Jr., Rahbar A, Odeberg J, Khan Z, Peredo I, Hamerlik P, Bartek J, Stragliotto G, Landazuri N, Söderberg-Naucler C. Cytomegalovirus infection induces a stem cell phenotype in human primary glioblastoma cells: prognostic significance and biological impact. 2016;23(2):261-9.

Oncoimmunology

Rahbar A, Cederarv M, Wolmer-Solberg N, Tammik C, Stragliotto G, Peredo I, Fornara O, Xu X, Dzabic M, Taher C, Skarman P, Söderberg-Naucler C. Enhanced neutrophil activity is associated with shorter time to tumor progression in glioblastoma patients. 2016;5(2):e1075693.

Oncoimmunology

Rahbar A, Peredo I, Solberg NW, Taher C, Dzabic M, Xu X, Skarman P, Fornara O, Tammik C, Yaiw K, Wilhelmi V, Assinger A, Stragliotto G, Söderberg-Naucler C. Discordant humoral and cellular immune responses to Cytomegalovirus (CMV) in glioblastoma patients whose tumors are positive for CMV. 2015;4(2):e982391.

Oncoimmunology.

Fornara O, Odeberg J, Wolmer Solberg N, Tammik C, Skarman P, Peredo I, Stragliotto G, Rahbar A, Söderberg-Naucler C. Poor survival in glioblastoma patients is associated with early signs of immunosenescence in the CD4 T-cell compartment after surgery. 2015;4(9):e1036211.

Description of Research

Turku Cellular Microbiology Laboratory (TCML) studies molecular mechanisms of the bacterial pathogen-host cell interaction. We aim to understand how host cell signaling is regulated in bacterial infection to orchestrate pathogen clearance, and how pathogen utilizes protein secretion systems and their effector proteins to counterattack this host anti-bacterial response. We utilize animal experimentation, cell culture models and a range of biochemical and biophysical methods of protein chemistry to understand bacterial infection at the molecular level. Our ultimate goal is to gain molecular knowledge allowing development of new and targeted therapeutic solutions to bacterial infections, and potentially also to other inflammatory disorders.

Current topics

ADP-ribosylation signaling in gastrointestinal tract infections
Mammalian ADP-ribosylating PARP enzymes
Bacterial ADP-ribosylating toxins
Bacterial toxin-targeted drug modalities

Research group members

Senior researchers: Rita Azevedo, Anbu Poosakkannu
PhD students: Moona Miettinen, Madhukar Vedantham
Other students: Olli Laaksoaho, Vili Niinikoski, Arttu Laisi, Antti Kaatiala, Alaa Benkherouf
Technicians: Mika Savisalo

Recent key publications

Paramonov, V.M., Sahlgren, C., Rivero-Müller, A., and Pulliainen, A.T. (2020) iGIST - a kinetic bioassay for pertussis toxin based on its effect on inhibitory GPCR signaling. ACS Sensors (in press)
Eskonen, V., Tong-Ochoa, N., Mattsson, L., Miettinen, M., Lastusaari, M., Pulliainen, A.T., Kopra, K., and Härmä H. (2020) Single-peptide TR-FRET detection platform for cysteine-specific post-translational modifications. Analytical Chemistry 92:13202-13210.
Ashok, Y., Miettinen, M, De Oliveira, D.K.H., Tamirat, M.Z., Näreoja, K., Tiwari, A., Hottiger, M.O., Johnson, M.S., Lehtiö, L. and Pulliainen, A.T. (2020) Discovery of compounds inhibiting the ADP-ribosyltransferase activity of pertussis toxin. ACS Infectious Diseases 6:588-602. (in the special issue of Chemical Microbiology)
Kopra, K., Vuorinen, E., Abreu-Blanco, M., Wang, Q., Eskonen, V., Gillette, W., Pulliainen, A.T., Holderfield, M., and Härmä H. (2020) Homogeneous dual-parametric coupled assay for simultaneous nucleotide exchange and KRAS/RAF-RBD interaction monitoring. Analytical Chemistry 92:4971-4979.
Miettinen, M., Vedantham, M., and Pulliainen, A.T. (2019) Host poly(ADP-ribose) polymerases (PARPs) in acute and chronic bacterial infections. Microbes and Infection 21:423-431. (invited review)

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Pia Rantakari: Endothelium and embryonic leukocyte migration

Pia Rantakari, Adjunct Professor of Physiology, Academy Research Fellow

Contact: pia.rantakari@utu.fi

Description of Research

Our research emphasis is on endothelium's involvement in fetal leukocyte cell migration and the outcome of impaired embryonic leukocyte migration in adult tissue homeostasis. We are particularly interested in the tissue-resident macrophages and whether diverse developmental origin among resident macrophages relates to macrophages' postnatal functions. We use single-cell genomics with single-cell proteomics combined with various sophisticated in vivo mouse models to answer our research question.

Current topics

The function of the endothelium and molecular steps underlying the leukocyte migration during embryogenesis
Understanding how the ontogeny relates to the function of macrophages under homeostatic conditions or in diseases
Cross-talk of Immune and endocrine system

Research group members

Senior researchers: Heli Jokela, Heidi Gerke
PhD students: Emmi lokka, Ines Felix, Laura Lintukorpi, Elias Mokkala
Other students: Venla Ojasalo, Joonas Karhula, Elina Laine
Technicians: Laura Grönfors, Etta-Liisa Väänänen

Recent key publications

Lokka E, Lintukorpi L, Cisneros-Montalvo S, Mäkelä A-T, Tyystjärvi S, Ojasalo O, Gerke H, Toppari J, Rantakari P# and Salmi M# Generation, localization and functions of macrophages during the maturation of testis. Nature Communications 2020. PMID:32873797.
Jokela H, Lokka E, Kiviranta M, Tyystjärvi S, Gerke H, Elima K, Salmi M# and Rantakari P#. Fetal –derived macrophages persist and sequentially maturate in ovaries after birth. Eur J Immunol. 2020. PMID:32459864.
Jäppinen N, Felix I, Lokka E, Tyystjärvi S, Pynttäri A, Lahtela T, Gerke H, Elima K, Rantakari P, Salmi M. Fetal-derived macrophages dominate in adult mammary glands. Nature Communications 2019. PMID:30655530.
Rantakari P, Jäppinen N, Lokka E, Mokkala E, Gerke H, Peuhu E, Ivaska J, Elima K, Auvinen K, Salmi M. Fetal liver endothelium regulates the seeding of tissue-resident macrophages. Nature 2016. PMID:27732581.
Rantakari P, Patten DA, Valtonen J, Karikoski M, Gerke H, Dawes H, Laurila J, Ohlmeier S, Elima K, Hübscher SG, Weston CJ, Jalkanen S, Adams DH, Salmi M, Shetty S. Stabilin-1 expression defines a subset of macrophages that mediate tissue homeostasis and prevent fibrosis in chronic liver injury. Proc Natl Acad Sci U S A. 2016. PMID:27474165.

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Marko Salmi: Leukocyte traffic and the immune response

Marko Salmi, MD, PhD, Professor of Molecular Medicine

Contact: marko.salmi@utu.fi

Description of Research

Our aim is to elucidate how the immune responses are regulated in health and disease. We focus on the mechanisms governing the trafficking and differentiation of leukocytes. We are also interested in dissecting the different routes of antigen transport to lymph nodes. Based on our discoveries we develop new approaches for therapeutic manipulation of immune responses in inflammatory and malignant diseases. As a separate line of research, we analyze the value of adhesion molecules and cytokines as biomarkers of disease in population and patient cohorts.

Current topics

antigen transcytosis in lymph nodes
the effects of cell origin and tissue niche in differentiation of myeloid leukocytes
immunological biomarkers of inflammation and cancer

Research group members

Senior researchers: Jonna Alanko, Ruth Fair-Mäkelä
PhD students: Henrik Elenius, Ines Felix, Laura Kähäri, Joni Laakkonen, Laura Lintukorpi, Emmi Lokka, Pia Sundqvist, Pinja Thoren
Other students: Aino Elomaa
Technicians: Etta-Liisa Virtomaa

Recent key publications

Rantakari P, Auvinen K, Jäppinen J, Kapraali M, Valtonen J, Karikoski M, Gerke H, , IIftakhar-E-Khuda I, Keuschnigg J, Umemoto E, Tohya K, Miyasaka M, Elima K, Jalkanen S, Salmi M. Plvap controls the entry of antigens to conduits and lymphocyte transmigration to parenchyma in the lymphatic sinus of lymph nodes. Nat Immunol 16:386-96, 2015.
Rantakari P, Jäppinen N, Lokka E, Mokkala E, Gerke H, Peuhu E, Ivaska J, Elima K, Auvinen K, Salmi M.. Fetal liver endothelium regulates the seeding of tissue-resident macrophages. Nature, 538:392-396, 2016.
Santalahti K, Havulinna A, Maksimow M, Zeller T, Blankenberg S,Vehtari A, Joensuu H, Jalkanen S, Salomaa V, Salmi M. Plasma levels of HGF and PlGF predict mortality in a general population: a prospective cohort study. J Intern Med, 282(4):340-352, 2017.
Kähäri L, Fair-Mäkelä R, Auvinen K, Rantakari P, Jalkanen S, Ivaska J, Salmi M. Transcytosis route mediates rapid delivery of intact antibodies to draining lymph nodes. J Clin Invest. 129:3086-3102, 2019.
Lokka E, Lintukorpi L, Cisneros-Montalvo S, Mäkelä JA, Tyystjärvi S, Ojasalo V, Gerke H, Toppari J, Rantakari P, Salmi M. Generation, localization and functions of macrophages during the development of testis. Nat Commun. 2020 Sep 1;11(1):4375. doi: 10.1038/s41467-020-18206-0.

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Petri Susi: Virus evolution, tropism and pathogenesis

Petri Susi, Dr

Contact: pesusi@utu.fi

Description of Research

The picornavirus laboratory focuses on relation between picornavirus genome variation and pathogenesis. We develop rapid and feasible methods for the detection, typing and genome sequencing of human entero-, rhino- and parechoviruses, which allow identification of disease-causing clinical isolates. Through genome analyses and cellular assays, we aim to establish the link between receptor-mediated cellular infectivity, tissue pathogenicity and immune responses. The ultimate aim is to identify viral and cellular determinants for development of novel diagnostics and counter measures against picornaviral diseases. Conversely, the information may also be useful in development of picornaviruses for oncolytic virotherapy.

Current topics

Workflow for rapid genome sequencing of human picornaviruses
Novel diagnostic and typing methods
Characterization of echovirus 7 isolates including Rigvir oncolytic virotherapy virus
Broad range neutralizing and detector antibody development

Research group members

PhD students: Eero Hietanen, Juha Koskinen

Recent key publications

Hietanen E. & Susi, P. 2020. Recombination events and conserved nature of RGD receptor binding motifs in coxsackievirus A9 isolates. Viruses 12, 68. https://doi.org/10.3390/v12010068
Kainulainen, V., Elf, S., Susi, P., Mäki, M., Pitkäranta, A., Koskinen, J., Korpela R., & Eboigbodin, K. 2019. Detection of rhinoviruses with reverse transcription strand invasion based amplification method (RT-SIBA). Journal of Virological Methods 263, 75-80. https://doi.org/10.1016/j.jviromet.2018.10.015
Hietanen, E., Smura, T., Hakanen, M., Chansaenroj, J., Merilahti, P., Poovorawan, Y., Nevalainen, J., Pandey, S., Pursiheimo, J. & Susi, P. 2018. Genome sequences of RIGVIR oncolytic virotherapy virus and other echovirus 7 isolates. Genome Announcements 6: e00317-18. https://doi.org/10.1128/genomeA.00317-18
Heikkilä, O., Merilahti, P., Hakanen, M., Karelehto. E., Alanko, J., Sukki, M., Kiljunen, S. & Susi, P. 2016. Integrins are not essential for entry of coxsackievirus A9 into SW480 human colon adenocarcinoma cells. Virology Journal 13, 171. https://doi.org/10.1186/s12985-016-0619-y
Ylä-Pelto, J., Tripathi, L. & Susi, P. 2016. Therapeutic use of native and recombinant enteroviruses. Viruses 8, 57. https://doi.org/10.3390/v8030057

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Akira Takeda: Immune and structural cell interaction in health and disease

Akira Takeda, Academy Research Fellow

Contact: akitak@utu.fi

Description of research

Although immune cells play a critical role in human diseases such as infection and cancer, structural cells including endothelial and stromal cells are also crucial for maintaining the function of the immune cells. Recent single-cell technologies showed multiple heterogenous subsets in structural cells that have not been considered before. The aim of our group is (1) to find unrecognized heterogeneous structural cell subsets in human organs including lymphoid organs and tumors using single-cell technologies, and (2) to find the new molecular mechanism between heterogeneous structural cells and immune cells in health and disease.

Current topics

Heterogeneity of human dendritic cells and their functions
Blood and lymphatic endothelial cell heterogeneity in the tumor microenvironment
Lymphatics in human spleen

Research group members

PhD student: Diana Lehotina
Research assistant: Sadaf Fazeli

Recent selected publications

Takeda A, Hollmén M, Dermadi D, Pan J, Brulois KF, Kaukonen R, Lönnberg T, Boström P, Koskivuo I, Irjala H, Miyasaka M, Salmi M, Butcher EC, Jalkanen S: “Single-Cell Survey of Human Lymphatics Unveils Marked Endothelial Cell Heterogeneity and Mechanisms of Homing for Neutrophils.” Immunity 51: 561-572, 2019.
Takeda A, Kobayashi D, Aoi K, Sasaki N, Sugiura Y, Igarashi H, Tohya K, Inoue A, Hata E, Akahoshi N, Hayasaka H, Kikuta J, Scandella E, Ludewig B, Ishii S, Aoki J, Suematsu M, Ishii M, Takeda K, Jalkanen S, Miyasaka M, Umemoto E: “Fibroblastic reticular cell-derived lysophosphatidic acid regulates confined intranodal T-cell motility.” eLIFE 5: e10561, 2016.
Takeda A, Hossain MS, Rantakari P, Simmons S, Sasaki N, Salmi M, Jalkanen S, Miyasaka M: “Thymocytes in Lyve1-CRE/S1pr1f/f mice accumulate in the thymus due to cell-intrinsic loss of sphingosine-1-phosphate receptor expression.” Frontiers in Immunology, 7, 2016.
Xiang M, Grosso RA, Takeda A, Pan J, Bekkhus T, Brulois K, Dermadi D, Nording S, Vanlandewijck M, Jalkanen S, Ulvmar MH#, Butcher EC# (#equally contributed senior authors): “A single-cell transcriptional roadmap of the mouse and human lymph node lymphatic vasculature.” Frontiers in Cardiovascular Medicine 7, 2020.
Takeda A, Jalkanen S: “Single-cell transcriptomics of human lymph node stroma.” STAR Protocols, 2020. doi: 10.1016/j.xpro.2020.100021

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Sisko Tauriainen: Parechovirus epidemiology and pathogenesis

Sisko Tauriainen

Matti Waris: Host response and molecular variation in respiratory and enteric virus infections

Matti Waris

Jaana Vuopio: Molecular epidemiology, carriage and antimicrobial susceptibility of bacterial pathogens

Jaana Vuopio