Harri Alenius

Harri Alenius

Professor

Email:
harri.alenius@ki.se
Organisation:

About me

Harri Alenius is Professor of Molecular Toxicology and Head of the Systems Toxicology Unit at the Institute of Environmental Medicine, Karolinska Institutet.

He was born in 1966 in Tampere, Finland, and studied Cellular and Molecular Biology at Jyväskylä University, graduating in 1995. He got PhD in Tampere University in 1997. He conducted research at the Finnish Institute of Occupational Health (FIOH) from 1996–2016 and appointed as Research Professor in 2005. Alenius was a postdoc at Children’s Hospital, Harvard Medical School from 1998–2000.

On August 2016, he was appointed as a full Professor of Molecular Toxicology at Karolinska institutet. Alenius is also chairman of the expert panel of SweNanoSafe - the national platform for nanosafety.

Research description

My research interest  is to investigate how different environmental exposures affect human wellbeing, focusing on the impact of chemicals, allergens and microbes on immunity. I am particularly interested in how environmental toxicants and microbiota (the ecosystem of microorganisms) and human microbiota interact with each other, and how they affect the immune system and contribute health and disease.

I am leading and participating in several projects, focusing on the impact of host-microbiome interplay during immune homeostasis and dysregulation. My research combines data derived from the human cohorts and clinical studies with experiments on cell and animal models. Bioinformatics analysis, such as 16S and metagenomic approaches, and their integration with environmental exposure data, clinical data and other OMICs layers are applied in my research.

The major ongoing projects are briefly described below.

Project 1: Host-microbe interactions in atopic dermatitis and psoriasis

The two most common chronic inflammatory skin diseases are atopic dermatitis (AD) and psoriasis. The underpinnings of the remarkable degree of clinical heterogeneity of AD and psoriasis are poorly understood and, as a consequence, disease onset and progression are unpredictable and the optimal type and time-point for intervention are as yet unknown. The BIOMAP project (https://biomap-imi.eu) is the first IMI (Innovative Medicines Initiative) project dedicated to investigating the causes and mechanisms of AD and psoriasis and to identify potential biomarkers responsible for the variation in disease outcome. There is mounting evidence supporting an important role for microbial exposures and our microbiota as factors mediating immune polarization and AD and psoriasis pathogenesis. Therefore, the aim of the work package WP4 is to investigate skin and gut microbiome linked to AD or psoriasis. The BIOMAP project will enable the integration of patient cohorts, data and knowledge in unprecedented proportions. The project has a unique opportunity with a potential to bridge and fill the gaps between current problems and solutions.

The project is done in collaboration with docent Nanna Fyhrquist as well as with BIOMAP and MAARS consortium members. The project is funded by the IMI2 - Innovative Medicines Initiative.

Project 2: Karelia Allergy Study

The biodiversity hypothesis suggests that reduced exposure to diverse environmental microbes has resulted in the current increase in chronic inflammatory diseases, including allergy, in western societies. However, the mechanistic basis of the association between microbial diversity, faulty immune programming, and the risk of allergic disease remains largely unknown.

After the Second World War, populations living in the Karelia area were strictly divided by the border between Finland and Russia. This resulted in the evolution of starkly different lifestyles, standard of living and exposure to environmental microbes. The key finding of our previous study from Karelia was that allergic symptoms and diseases were dramatically more common in Finnish children and adults than in their Russian counterparts.

The Karelia Allergy Study cohort provides a unique opportunity to explore the role of the human microbiota in the development of allergy as well as in immune homeostasis.  Taking advantage of this exceptional study cohort, state-of-the-art OMICs methodologies and systems biology approaches we explore environment-gene interaction and molecular mechanisms underlying allergy protection and allergic sensitization.

The project is done in collaboration with docent Nanna Fyhrquist as well as with prof.emer Tari Haahtela and Karelia Allergy Study -team. The project is financed by the Swedish Research Council (Vetenskaprådet – Medicine and health).

 

Project 3: The role of host microbiota in chemically induced metabolic disruption

Increase in metabolic impairment correlates with industrialization and release of xenobiotic chemicals to the environment and the food chain. Dysbiosis of the gut microbiota is another risk factor of metabolic impairment. Although several environmental pollutants have shown to alter the gut microbiota, little is known regarding the link between chemical exposure, microbiota dysbiosis and impaired metabolic function.

We hypothesise that the interaction between xenobiotic chemicals and gut microbiota pose a critical mode of action (MoA) for metabolic disruption.

In this project we aim to: a) determine the impact of xenobiotic chemicals on the gut microbiota; b) investigate the effect of microbiota on host physiology in response to chemical exposure in gnotobiotic model and c) identify MoA underlying the link between chemically induced microbiota dysbiosis and metabolic disruption

Our proposal relies on the analysis of microbiota-host interactions, utilizing zebrafish embryo models to interrogate the effect of environmental pollutants on biological processes associated with metabolic disorders. We will identify key effect markers underlying metabolic disruption that can be utilized to establish an efficient and biologically relevant screening platform to interrogate metabolic disruptive potencies of environmental pollutants.

The project is done in collaboration with docent Emma Wincent and her group members. The project is financed by the Swedish Research Council for Sustainable Development (FORMAS).

 

Selected recent publications

  1. Fortino V, Kinaret PAS, Saarimäki L, Gallud A, Vales G, Correia M, Rasool O, Ytterberg J, Monopoli M, Skoog T, Ritchie P, Moya S, Vázquez-Campos S, Handy R, Grafström R, Tran L, Zubarev R, Lahesmaa R, Dawson K, Loeschner K, Husfeldt Larsen E, Krombach F, Norppa H, Kere J, Savolainen K, Alenius H, Fadeel B, Greco D. Biomarkers of nanomaterials hazard from multi-layer data. Nat Commun. 2022 Jul 1;13(1):3798.
  2. Ndika J, Karisola P, Lahti V, Fyhrquist N, Laatikainen T, Haahtela T, Alenius H. Epigenetic Differences in Long Non-coding RNA Expression in Finnish and Russian Karelia Teenagers With Contrasting Risk of Allergy and Asthma. Frontiers in Allergy. 2022. https://doi.org/10.3389/falgy.2022.878862
  3. Wisgrill L, Fyhrquist N, Ndika J, Paalanen L, Berger A, Laatikainen T, Karisola P, Haahtela T, Alenius H. Bet v 1 triggers antiviral-type immune signalling in birch-pollen-allergic individuals. Clin Exp Allergy 2022. doi: 10.1111/cea.14108. Online ahead of print.
  4. Karisola P, Palosuo K, Hinkkanen V, Wisgrill L, Savinko T, Fyhrquist N, Alenius H, Makela MJ. Integrative Transcriptomics Reveals Activation of Innate Immune Responses and Inhibition of Inflammation During Oral Immunotherapy for Egg Allergy in Children. Front Immunol 2021; 12:704633.
  5. Alenius H, Sinkko H, Moitinho-Silva L, Rodriguez E, Broderick C, Alexander H, Reiger M, Hjelmso MH, Fyhrquist N, Olah P, Bryce P, Smith C, Koning F, Eyerich K, Greco D, van den Bogaard EH, Neumann AU, Traidl-Hoffmann C, Homey B, Flohr C, Bonnelykke K, Stokholm J, Weidinger S. The power and potential of BIOMAP to elucidate host-microbiome interplay in skin inflammatory diseases. Exp Dermatol 2021; 30:1517-31.
  6. Haahtela T, Alenius H, Lehtimäki J, Sinkkonen A, Fyhrquist N, Hyöty H, Ruokolainen L, Mäkelä MJ. Immunological resilience and biodiversity for prevention of allergic diseases and asthma. Allergy. 2021 May 6. doi: 10.1111/all.14895. Online ahead of print.
  7. Werner P, Wisgrill L, Riskumaki M, Jalonen E, Vendelin J, Suomela S, Lauerma A, Alenius H, Fyhrquist N. Identification of novel miRNA-mRNA regulatory networks in contact dermatitis by integrated microarray analysis. Allergy 2021; 76:1257-61.
  8. Suojalehto H, Ndika J, Lindstrom I, Airaksinen L, Karisola P, Alenius H. Endotyping asthma related to 3 different work exposures. J Allergy Clin Immunol 2021;148:1072-80.
  9. Riskumäki M, Tessas I, Ottman N, Suomalainen A, Werner P, Karisola P, Lauerma A, Ruokolainen L, Karkman A, Wisgrill L, Sinkko H, Lehtimäki J, Alenius H, Fyhrquist N. Interplay between skin microbiota and immunity in atopic individuals. Allergy 2021; 76:1280-4.
  10. Palosuo K, Karisola P, Savinko T, Fyhrquist N, Alenius H, Makela MJ. A Randomized, Open-Label Trial of Hen's Egg Oral Immunotherapy: Efficacy and Humoral Immune Responses in 50 Children. J Allergy Clin Immunol Pract 2021; 9:1892-901 e1.
  11. Ottman N, Barrientos-Somarribas M, Fyhrquist N, Alexander H, Wisgrill L, Olah P, Tsoka S, Greco D, Levi-Schaffer F, Soumelis V, Schroder JM, Kere J, Nestle FO, Barker J, Ranki A, Lauerma A, Homey B, Andersson B, Alenius H. Microbial and transcriptional differences elucidate atopic dermatitis heterogeneity across skin sites. Allergy 2021; 76:1173-87.
  12. Ndika J, Karisola P, Kinaret P, Ilves M, Alenius H. Profiling non-coding RNA changes associated with 16 different engineered nanomaterials in a mouse airway exposure model. Cells. 2021 10(5):1085.
  13. Kinaret PAS, Ndika J, Marit I, Wolff H, Vales G, Norppa H, Savolainen K, Skoog T, Kere J, Moya S, Handy RD, Karisola P, Fadeel B, Greco D, Alenius H. Toxicogenomic Profiling of 28 Nanomaterials in mouse airways. Adv Sci (Weinh). 2021; 8:2004588.
  14. Wisgrill L, Werner P, Jalonen E, Berger A, Lauerma A, Alenius H, Fyhrquist N. Integrative transcriptome analysis deciphers mechanisms of nickel contact dermatitis. Allergy 2021; 76:804-15.
  15. Fortino V, Wisgrill L, Werner P, Suomela S, Lindere N, Jaloneng E, Suomalainen A, Marwah V,  Kero M, Pesonen M, Lundin J, Lauerma A, Aalto-Korte K, Greco D, Alenius H, Fyhrquist N. Machine learning driven biomarker discovery for the discrimination between allergic and irritant contact dermatitis. PNAS. 2020 Dec 14:202009192. Online ahead of print.
  16. Gallud A, Delaval M, Kinaret P, Marwah VS, Fortino V, Ytterberg J, Zubarev R, Skoog T, Kere J, Correia M, Loeschner K, Al-Ahmady Z, Ruiz J, Astruc D, Monopoli M, Handy R, Moya S, Savolainen K, Alenius H, Greco D, Fadeel B. Multi-parametric profiling of a large panel of engineered nanomaterials points to surface chemistry as a key determinant of nanomaterial effects. Adv Sci (Weinh). 2020 Oct 11;7(22):2002221.
  17. Ruokolainen L, Fyhrquist N, Laatikainen T, Auvinen P, Fortino V, Scala G, Jousilahti P, Karisola P, Vendelin J, Karkman A, Markelova O, Mäkelä MJ, Lehtimäki S, Ndika J, Ottman N, Paalanen L, Paulin L, Vartiainen E, von Hertzen L, Greco D, Haahtela T, Alenius H. Immune-microbiota interaction in Finnish and Russian Karelia young people with high and low allergy prevalence. Clin Exp Allergy 2020 Oct;50(10):1148-1158. doi: 10.1111/cea.13728.
  18. Ndika J, Ilves M, Kooter IM, Grollers-Mulderij M, Duistermaat E, Tromp PC, Kuper F, Kinaret P, Greco D, Karisola P, Alenius H. Mechanistic Similarities between 3D Human Bronchial Epithelium and Mice Lung, Exposed to Copper Oxide Nanoparticles, Support Non-Animal Methods for Hazard Assessment. Small 2020:e2000527. doi: 10.1002/smll.202000527. Online ahead of print.
  19. Fyhrquist N, Muirhead G, Prast-Nielsen S, Jeanmougin M, P. O, Skoog T, Jules-Clement G, Feld M, Barrientos-Somarribas M, Sinkko H, van den Bogaard E, Zeeuwen P, Ricken G, Schalkwijk J, Niehues H, Däubener W, Eller S, Alexander H, Pennino P, Suomela S, Tessas I, Lybeck E, Baran A, Darban H, Singh Gangwar R, Gerstel U, Jahn K, Karisola P, Yan L, Hansmann B, Katayama S, Meller S, Bylesjö M, Hupe P, Levi-Schaffer F, Greco D, Ranki A, Schroeder J, Barker J, Kere J, Tsoka S, Lauerma A, Soumelis V, Nestle F, Homey B, Andersson B, Alenius H. Microbe-host interplay in atopic dermatitis and psoriasis. Nat Commun. 2019 Oct 16;10(1):4703. doi: 10.1038/s41467-019-12253-y.
  20. Ndika J, Seemab U, Poon WL, Fortino V, El-Nezami H, Karisola P, Alenius H. Silver, titanium dioxide and zinc oxide nanoparticles trigger miRNA/isomiR expression changes in THP-1 cells that are proportional to their health hazard potential. Nanotoxicology 2019 Sep 13:1-16. doi: 10.1080/17435390.2019.1661040.
  21. Ilves M, Kinaret PAS, Ndika J, Karisola P, Marwah V, Fortino V, Fedutik Y, Correia M, Ehrlich N, Loeschner K, Besinis A, Vassallo J, Handy RD, Wolff H, Savolainen K, Greco D, Alenius H. Surface PEGylation suppresses pulmonary effects of CuO in allergen-induced lung inflammation. Part Fibre Toxicol 2019; 16:28.
  22. Kooter I, Ilves M, Grollers-Mulderij M, Duistermaat E, Tromp PC, Kuper F, Kinaret P, Savolainen K, Greco D, Karisola P, Ndika J, Alenius H. Molecular Signature of Asthma-Enhanced Sensitivity to CuO Nanoparticle Aerosols from 3D Cell Model. ACS Nano 2019; 13:6932-46.
  23. Karisola P, Suomalainen A, Fortino V, Ottman N, Vendelin J, Wolff HJ, Ruokolainen L, Greco D, Fyhrquist N, Alenius H. Tape-stripping alters the microbe-host correlations in mouse skin. Allergy 2019; 74:617-21.
  24. Ottman N, Ruokolainen L, Suomalainen A, Sinkko H, Karisola P, Lehtimaki J, Lehto M, Hanski I, Alenius H, Fyhrquist N. Soil exposure modifies the gut microbiota and supports immune tolerance in a mouse model. J Allergy Clin Immunol 2019; 143:1198-206 e12.

Links

Professor presentation