Group leader

Annika Meinander, Docent, PhD
Senior university lecturer in cell biology

Group Members

Anna Aalto, PhD student
Gabriela Martinez-Chacon, postdoc
Aravind Kumar Mohan, PhD student
Emmi Virtanen
Anna Dahlström
Veera Luukkonen
Elinda Hermanson
Emelie Hallberg

Contact information

Faculty of Science and Engineering
Cell Biology
BioCity, 2^nd floor
Tykistokatu 6
FI-20520 Turku
Finland
Tel. +358 469201699
Email: annika.meinander@abo.fi

Research focus

Cells need to sense and survive various stress conditions to maintain tissue homeostasis. Deregulation of these sensing mechanisms leads to disease such as chronic inflammation and cancer. The NF-κB family of transcription factors are activated as a response to recognition of danger signals from pathogens and harmful molecules, as well as during cell stress conditions including hypoxia and mechanical strain.

These transcription factors are major mediators of inflammatory gene expression promoting survival of the signal recognising cell and cells in surrounding tissues. As chronic inflammation is caused by defects in regulation of inflammatory signalling, flexible but precise mechanisms are needed to control inflammation-promoting signals in cells.

Post-translational modifications, such as ubiquitination regulate protein functions, and we aim at controlling NF-κB activation by regulating ubiquitin signalling. My research group use mammalian and non-mammalian model systems to identify changes in and consequences of ubiquitin-modifications in the evolutionary conserved intestinal epithelial barrier cell lining during local inflammation and cell stress.

We aim to generate fundamental knowledge in how ubiquitin modifications are regulated and recognized, and how this signal is converted into inflammation-inducing activation of gene expression. Our goal is to control stress-induced and inflammation-associated survival and proliferation by regulating transcriptional responses to maintain cell integrity and tissue homeostasis.

Ongoing Projects

Ubiquitination-mediated regulation of intestinal inflammation

Ubiquitination-mediated regulation of cell stress and infection

Targeting Met1-ubiqutination in inflammation-induced cancer

Caspase-mediated regulation NF-kappa activation

Development of aptamers for ubiquitin detection

Mechanical forces regulating tissue function and repair (CellMech)

Collaboration

• The InFLAMES Flagship (Innovation Ecosystem based on the Immune System), University of Turku and Åbo Akademi University. PI associated with flagship
• Centre of Excellence on Mechanostasis (CellMech) at Åbo Akademi University 2019-2023. Prof. Cecilia Sahlgren (chair), Prof. Lea Sistonen, Prof. John Eriksson, Prof. Diana Toivola, Dr. Guillaume Jaquemet and Dr. Malin Åkerfelt.
• ÅAU research profile Solutions for health: (https://drugdevelopment.fi)
• Animal models for studying intestinal inflammation: Ass. Prof. Diana Toivola (ÅAU, and Turku Center for Disease Modeling, https://www.tcdm.fi/facilities-and-services/intestinal-diseases-unit/)
• Development and validation of in vivo models for testing the antibacterial activity of nanoantibiotics: Prof. Jessica Rosenholm (ÅAU), Didem Sen Karaman (İzmir Katip Celebi University, Turkey)
• COST Action CA20113/ProteoCure, Management Committee member
• International network specialized in ubiquitin signalling: Prof. Mads Gyrd-Hansen (LEO Foundation Skin Immunology Research Center, University of Copenhagen, Denmark), Prof. Henning Walczak (UCL, London) and Prof. Pascal Meier (Institute of Cancer Research, London).
• National network for Drosophila work: Prof. Ville Hietakangas (University of Helsinki), Dr. Minna Poukkula (University of Helsinki), Dr. Susanna Valanne and Prof. Mika Rämet (University of Tampere).

Funding

The Academy of Finland
The Sigrid Jusélius Foundation
The Magnus Ehrnrooth Foundation
The Liv och Hälsa Foundation
The Doctoral Network of Molecular Biosciences (MolBio)

Selected publications

Mung KL, Meinander A, Koskinen P. (2022) PIM kinases phosphorylate lactate dehydrogenase A at serine 161 and suppress its nuclear ubiquitination. FEBS J. In press. doi: 10.1111/febs.16653

Kietz C, Meinander A. (2022) Caspases as guardians of Drosophila innate immune responses. Cell Death Differ. In press. doi: 10.1038/s41418-022-01038-4.

Aalto A, Martínez-Chacón G, Kietz C, Tsuganova N, Sundén M, Broemer M, Meinander A. (2022) M1-ubiquitination facilitates NF-kappaB activation and survival during sterile inflammation, FEBS J. 289: 5180-5197. doi: 10.1111/febs.16425. This is the first description of the role of Met1-ubiquitination in cell stress. Here we show that Met1Ub chains are required for both flies and human cells to protect themselves against severe cell stress. Editor’s Choice article from the 06 September 2022 issue. Highlighted by Peltzer N: Linear ubiquitin as a common regulator of cellular stress. doi: 10.1111/febs.16427

 West G, Turunen M, Aalto A, Virtanen L, Li S-P, Heliö TM, Meinander A, Taimen P. (2022) Proteasome dysfunction leads to enhanced autophagy mediated degradation of mutant lamin A/C. Front. Cell Dev. Biol. 10:932983. doi: 10.3389/fcell.2022.932983

Şen Karaman D, Kietz C, Govardhanam P, Slita A, Menea A, Pamukçu A, Meinander A, Rosenholm J. (2022) Core@shell structured ceria@mesoporous silica nanoantibiotics restrain bacterial growth in vitro and in vivo. Biomater Adv. (Mater. Sci. Eng., C) 133:112607. doi: 10.1016/j.msec.2021.112607. Here we describe the development and evaluation of mesoporous silica nanocomposites as nanoantibiotics against E. coli in Drosophila. In this collaboration, we optimised Drosophila larvae to be used as a model to study effects of nanoantibiotics in vivo.

Kietz C, Mohan AK, Pollari V, Tuominen I-E, Ribeiro PS, Meier P, Meinander A. (2021) Drice restrains Diap2-mediated inflammatory signalling and intestinal inflammation. Cell Death Differ. 29:28-39. doi: 10.1038/s41418-021-00832-w. Here we describe new roles for effector caspases in immune regulation. We found IAP-mediated spontaneous activation of inflammatory signalling to be restrained by caspases, and that this is important to for the intestinal epithelium to tolerate the commensal microbiome.

Qiao X, Liu Y, Llamazares Prada M, Mohan A, Gupta A, Jaiswal A, Sharma M, Haikala H, Talvinen K, Yetukuri L, Pylvänäinen JW, Klefström J, Kronqvist P, Meinander A, Aittokallio T, Hietakangas V, Eilers M, Westermarck J. (2020) UBR5 is co-amplified with MYC in breast tumors and encodes an ubiquitin ligase that limits MYC-dependent apoptosis. Cancer Res. 80:1414-1427. doi: 10.1158/0008-5472.CAN-19-1647

 Aalto A, Mohan AK, Schwintzer L, Kupka S, Walczak H, Broemer M, Meinander A. (2019) M1-linked ubiquitination by LUBEL is required for inflammatory responses to oral infection in Drosophila. Cell Death Differ. 26: 860–876. doi: 10.1038/s41418-018-0164-x. Here we show Met1-ubiquitination to be a conserved part of NF-kappaB regulation. We found the Drosophila linear ubiquitin ligase LUBEL to be necessary and sufficient for intestinal immune responses in Drosophila.

Kietz C, Pollari V, Meinander A. (2018) Generating Germ-Free Drosophila to Study Gut-Microbe Interactions: Protocol to Rear Drosophila under Axenic Condition. Curr. Protoc. Toxicol. 77:e52. doi: 10.1002/cptx.52

 Gullmets J, Torvaldson E, Lindqvist J, Imanishi SY, Taimen P, Meinander A*, Eriksson JE*. (2017) Internal epithelia in Drosophila display rudimentary competence to form cytoplasmic networks of transgenic human vimentin. FASEB J. 12: 5332-5341. doi: 10.1096/fj.201700332R *equal contribution. Here we describe cytoplasmic intermediate filament compatibility in the different types of epithelial cell layers in Drosophila.

Sahlgren C, Meinander A, Zhang H, Cheng F, Preis M, Xu C, Salminen TA, Toivola D, Abankwa D, Rosling A, Karaman DŞ, Salo-Ahen OMH, Österbacka R, Eriksson JE, Willför S, Petre I, Peltonen J, Leino R, Johnson M, Rosenholm J, Sandler N. (2017) Tailored Approaches in Drug Development and Diagnostics: From Molecular Design to Biological Model Systems. Adv. Healthcare Mater. 6: 1700258. doi: 10.1002/adhm.201700258

Meinander A, Runchel C, Tenev T, Chen L, Kim C-H, Ribeiro PS, Broemer M, Leulier F, Zvelebil M, Silverman N and Meier P. (2012) Ubiquitylation of the Initiator Caspase Dredd is Required for Innate Immune Signalling.  EMBO J. 31: 2770-2783. doi: 10.1038/emboj.2012.121. Here we show for the first time that initiator caspase activity is regulated by ubiquitination. It provides critical knowledge in how ubiquitin signalling can tune inflammatory NF-κB signalling. Highlighted by Falschlehner C & Boutros M: Innate immunity: regulation of caspases by IAP-dependent ubiquitylation. doi: 10.1038/emboj.2012.148

Rosenholm JM, Meinander A, Peuhu E, Niemi R, Eriksson JE, Sahlgren CM, and Lindén M. (2009) Targeting of porous hybrid silica nanoparticles to cancer cells. ACS Nano. 3: 197-206. doi: 10.1021/nn800781r

Meinander A, Söderström TS, Kaunisto A, Poukkula M, Sistonen L, and Eriksson JE. (2007) Fever-like hyperthermia controls T-lymphocyte persistence by inducing degradation of c-FLIPshort. J. Immunol. 178: 3944-3953. doi: 10.4049/jimmunol.178.6.3944

Tran SEF, Meinander A, and Eriksson JE. (2004) Instant decisions: transcription-independent control of death receptor-mediated apoptosis. Trends Biochem. Sci. 11: 601-606. doi: 10.1016/j.tibs.2004.09.009

Research environment

The Åbo Akademi University life sciences laboratories are active on the Kupittaa campus together with the life sciences and medical researchers from University of Turku and Turku University Hospital. Research in life sciences at Åbo Akademi University is supported by strong organizations such as BioCity Turku and Health Campus Turku, which strengthen the opportunities for collaboration and innovation on our campus. We also have access to advanced state of the art infrastructure through Turku Bioscience, Turku BioImaging and EuroBioimaging. We are also part of the ÅAU Center of Excellence project CellMech (Center of Excellence in Cellular Mechanostasis).