Intermediate Filaments in Tissue Repair
Intermediate filament (IF) proteins are encoded by the largest gene family among three cytoskeletal protein groups, with more than 70 members that show remarkable diversity in sequences, expression patterns, and distribution in various tissues.
Failed Intermediate Filament functions show a repertoire of phenotype that reflect severely compromised tissue repair. Even normal IF-mediated repair functions may become maladaptive with pathological consequences, including fibrosis and aberrant tissue regeneration.
Our aim is to define molecular mechanisms in advanced cell and organ systems and obtain proof of concept by physiologically relevant in vivo processes, including wound healing, vascular repair, intestinal injuries, cardiac impairment and injury, and breast tissue remodeling. The studies also include applicable disease states.
John E. Eriksson
IFs as signaling hubs in tissue repair
Prof. John E. Eriksson (PhD) is the Director of Turku Bioscience, Professor of Cell Biology at the ÅAU, Chair of Turku BioImaging, and current Interim Director General of Euro-BioImaging ERIC. Prof. Eriksson has made key discoveries especially related to intermediate filaments and signaling, coining the concept of intermediate filaments being able to act as signaling organizers and signal modulators. He has been one of the key persons involved in the establishment of Euro-BioImaging and has longstanding experience in a broad range of imaging technologies and infrastructures. He is a member of the Centre of Excellence of Cell Mechanostasis or CellMech at Åbo Akademi University, Turku (2019-24) and an elected member of the Finnish Society of Sciences and Letters and the Technical Science Academy of Finland. He has more than 180 per review publications, close to 10 000 citations, and a H-index of 59.
Key technologies and model systems: Determining the IF-based signaling proteomes in repair models, wound healing, and fibrosis.
Role in the team: Wound healing models, metabolic, cell growth, and cell size signaling, combining imaging with proteomics.
Cell fate and mechanobiology of the vasculature
Cecilia M. Sahlgren, (female, Co-director) is professor in Cell Biology at Åbo Akademi and affiliated professor in biomedical engineering at Eindhoven University of Technology. She leads the Centre of Excellence of Cell Mechanostasis “CellMech” at ÅAU, is an elected member of the Finnish Society of Sciences and Letters and the Technical Science Academy of Finland and the European Vascular Biology Organization. CS has a long-term international and interdisciplinary research focus on understanding the fundamental mechanisms, which guide cell fate and organization in tissue regeneration and disease. Together with collaborators within tissue engineering and drug delivery she utilizes this knowledge to develop material-based medical technologies for regenerative and cancer therapies. She holds an ERC-CoG grant on forces in the cardiovascular (CV) system. She has developed CV Organ on Chips and has made important discoveries on mechanisms of cell fate decisions in CV tissue homeostasis. Key technologies and model systems: Zebrafish and mouse models for cardiovascular development and disease, engineered microtissues, Organ on Chip technologies, innovative tools for vascular mechanobiology, microscopy, functionalized materials. Sahlgren has a total of 77 publications, 4765 citations (without self-citations) earning her an h-factor of 30 (from Scopus as of 24.09.2020).
Role in the team: Study the impact of hemodynamic forces on intermediate filaments in regulating cardiovascular tissue homeostasis.
Lamins in cardiomyopathy
Pekka Taimen is Associate Professor of Molecular pathology at Institute of Biomedicine, University of Turku and part-time Chief pathologist at Pathology Division, Turku University Hospital. He serves as the chair of International Academy of Pathology, Finnish Division 2020-2021. Prof. Taimen has over 20 years of experience in research related to nuclear lamins as well as in translational cancer research. His current focus is on inherited cardiac diseases caused by lamin mutations. Tight link with clinic allowing access to real world patient material and clinical follow-up data through clinical collaborators and Auria Biobank.
Key technologies and model systems: Taimen group has a significant number of tools for lamin research including patient-derived primary cell lines, LMNA-mutant mice and expression vectors. The group has expertise in high-resolution imaging, histology, biochemistry, iPSC-cardiomyocyte studies and mouse work.Role in the team and in the WPs: The material of Taimen group (lamin mutant patient-derived fibroblast lines, hiPSC-derived cardiomyocytes, knock-in mice and patient tissue material) and their expertise in histopathology, immunohistochemistry and cell culture models strengthen the methodological expertise of consortium especially on studies focusing on tissue injury/repair of cardiovascular system.
IFs in intestinal regeneration, inflammation and cancer
Diana M. Toivola (PhD) is an Associate Professor in Cell Biology (especially biological imaging, experimental models and animal physiology), at Biosciences in the Faculty of Science and Engineering at ÅAU, Turku. She has leading international expertise on the stress-protective roles of cytoskeletal keratin intermediate filaments in liver, intestine and pancreas with focus on simple epithelial keratins in repair. Her key findings related to the molecular and physiological understanding of intestinal inflammation, colorectal cancer, liver disease, pancreatitis and diabetes. She is running the international Master’s degree program in Biomedical imaging at ÅAU, is a member of the Centre of Excellence of Cell Mechanostasis at ÅAU, co-director of the Turku BioCity Research program the Receptor Program, and coordinates the Intestinal diseases Unit at the Turku center for Disease modeling.
Key technologies and model systems: Intestinal regeneration and disease modeling in mice (eg diabetic wounds, intestinal and pancreatic damage and repair), 3D culture.
Role in the team: 1. Expertise in IFs, especially epithelial biology and (simple epithelial and epidermal) keratin function and regulation. 2. Intestinal health and regeneration. 3. Murine disease and regeneration modeling.
Mammary gland dynamics as a repair model to study IF-ECM interactions
Emilia Peuhu is an Academy of Finland Research Fellow and Adjunct Professor at the Institute of Biomedicine, University of Turku. She started her independent research work in 2019 and has a strong background in developmental and cancer biology, mechanobiology, stem cell research, and in vivo models, advanced imaging techniques, and technology transfer. Her laboratory studies how tissue architecture, cell adhesion and mechanosensing regulate development, regeneration, and carcinogenesis in the mammary gland. She has previously developed methods for organoid culture, and quantitative image analysis of cells and tissues. Her published work includes 25 scientific publications with 1173 citations (h-index of 12).
Key technologies and model systems: Primary human and mouse tissues and cells of normal breast and breast cancer; Organoid culture; Confocal, multiphoton and light-sheet microscopy; Quantitative image analysis of clonality, cell mechanics and traction forces; 3D bioprinting.
Role in the team: Study of IF signaling in mechanosensing, and cell lineage determination in regenerating intestinal and mammary epithelium of transgenic mouse models; Validation of IF-related functions in human tissue injury and disease.
IF, cell sensing and cell migration
Guillaume Jaquemet started his Cell Migration Laboratory in 2019 at the Center of Excellence in Mechanosensing and Turku Bioscience Center. His research focuses on elucidating the mechanisms by which cells utilize protrusions to sense and communicate with their environment. These communications are a key step in the repair process. To this end, his research group combines high to super-resolution microscopy (including live-cell imaging, intravital microscopy, and super-resolution traction force microscopy), advanced image analyses as well as mass spectrometry strategies. GJ co-authored 28 publications (+4 preprints), including 9 where he is the corresponding author (1685 citations, h-factor of 21). Essential for this proposal, GJ has a solid track record for developing and applying new imaging methodologies to further the mechanistic understanding of cell biology (including deep learning-based analysis strategies). Recently his laboratory released the ZeroCostDL4Mic platform that enables biologists to use AI-based image analysis.
Key technologies and model systems: Endogenous tagging of molecules using CRISPR – TurboID and Mass-spec. Apply to various IF molecules ? or to IF molecule upon stimulus? – Microscopy – AI-based image analysis – Tool development – Cell-based model mostly including fibroblasts, cancer cells and endothelial cells – Microfluidic devices – Zebrafish (in particular intravital imaging). Github tools: https://github.com/guijacquemet
Role in the team: G.J will bring to the consortium expertise in quantitative imaging, endogenous tagging of molecules, deep-learning technologies, turboID labeling, and mass-spec data analyses.