Project is devided into following themes:
PI: dr hab. A. Rutkowska
Doctoral students: Klaudia Konieczna-Wolska, Katarzyna Sochacka
In this project, we use a novel bioactive fluoro analogue of 7α,25OHC in the cuprizone model of MS to investigate its myelination-enhancing properties. We will also investigate the molecular and cellular mechanisms behind 7α,25OHC-induced remyelination in the organotypic cerebellar slice model and the effects of increased EBI2/7α,25OHC signalling on the function of primary oligodendrocyte progenitor cells, astrocytes and microglia using EBI2 KO mice.
This project received funding from the National Science Centre under SONATA 18 call, grant registration number: 2022/47/D/NZ3/02613
PI: dr hab. A. Rutkowska
Doctoral students: Fionä Caratis
The aims of this project are to investigate if EBI2 and enzymes necessary for its ligand’s synthesis (CH25H, CYP7B1) and degradation (HSD3B7) are present in the cells that form the blood-brain barrier (BBB) in mouse and human brain and if the expression of these enzymes in the BBB is altered in MS. We will attempt to modulate the EBI2-mediated chemotaxis of MS patient-derived CD4+ T cells via our human tri-cell BBB in vitro models. We will identify protein-protein interactions in healthy and MS cerebrospinal fluid (CSF) and quantify the levels of EBI2 receptor, its ligand 7α,25OHC and synthesising and degrading enzymes in the patient’s blood and CSF samples with the aim of identifying new biomarkers.
This project is being carried out in partnership with Prof. Tomomi Furihata, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan
This project received funding from the National Science Centre under OPUS 17 call, grant registration number: 2019/33/B/NZ4/03000.
Grantee/Student: M. Opielka;
Scientific Advisors: Prof. B. Karaszewski, dr hab. A. Rutkowska
Elucidating the Role of Proton-Activated G Protein-Coupled Receptors in Neuroinflammation and Oligodendrocyte Function: Implications for Remyelination in Multiple Sclerosis:
To maintain pH homeostasis, cells are required to sense acidic changes in their environment and respond accordingly. A T cell death-associated gene 8 (TDAG8, GPR65) has been shown to sense extracellular protons and stimulate differing signalling pathways. The expression of TDAG8 in normal tissue is primarily restricted to immune cells and often upregulated in solid tumors. However, high-powered GWAS studies identified TDAG8 as a candidate risk gene for multiple sclerosis (MS) and inflammatory bowel disease (IBD). While the function of TDAG8 in IBD has been repeatedly investigated only one study examined the effects of TDAG8 deficiency in the experimental autoimmune encephalomyelitis (EAE) model of MS. This project will further examine the role of TDAG8 in the pathophysiology of MS by employing a relapsing EAE model of MS.
This project is being carried out in partnership with Prof. Gerhard Rogler, Dr. Martin Hausmann and Dr. Cheryl DeVallière, University Hospital Zurich and University of Zurich, Switzerland
PI: dr hab. A. Rutkowska
Doctoral student: Piotr Pobiarzyn
Student: Agnieszka Baranowska
This project is being carried out in partnership with Dr. Sinéad O’Sullivan, German Center for Neurodegenerative Disease (Deutsches Zentrum für Neurodegenerative Erkrankungen, DZNE), Bonn, Germany
PI: dr hab. A. Rutkowska
Student : Oliwier Krajweski
Piezo1 is an ion channel that responds to mechanical cues and plays a regulatory role in various nervous system processes, including axonal growth, glial cell activation and oligodendrocyte progenitor cell (OPC) biology. The primary objective of the project is to explore the impact of pharmacological activation and inhibition of Piezo1 on oligodendrocyte differentiation and normal myelin development in the central nervous system. To achieve this goal, we are using primary cell cultures to investigate how Piezo1 influences the differentiation of OPCs into mature oligodendrocytes. In the organotypic cerebellar slice model, we are studying the impact of Piezo1 on myelination in a more complex environment resembling the central nervous system. By combining these approaches, we will gain insights into the relationship between Piezo1 and myelin development as well as its potential to rebuild myelin under pathophysiological conditions. The findings from this study may contribute to our understanding of myelin formation and could potentially lead to the development of new therapeutic strategies for demyelinating diseases.
This project is being carried out in partnership with Dr. Maria Velasco-Estevez, Spanish National Cancer Research Center (Centro Nacional de Investigaciones Oncológicas, CNIO), Madrid, Spain
The study will involve patients from the University Clinical Centre who have been diagnosed with multiple sclerosis.In-vivo myelin quantification enables us to divide patients into “good” and “bad” remyelinators. To achieve this goal, the methods need to be highly accurate and specific. In the literature a plenty of myelin-specific methods were described but none of them were applied in clinical routine. In our project we intend to quantify myelin employing the most promising myelin-specific MRI techniques, including myelin water imaging (MWI) and inhomogeneous magnetization transfer (ihMT). Myelin water has specific properties and localization. It is trapped between lipid layers of myelin and its time T2 is shorter than T2 time for intra and extracellular water. Postprocessing of registered signal allow as to determine the contribution of myelin water to the total MRI signal in specific voxel. IhMT technique is used to study the exchange of magnetization between free water molecules and water molecules bound to macromolecules (such as proteins and lipids) in tissues. Both examinations will be conducted using a 3T MRI scanner equipped with fast sequences, allowing for clinically reasonable measurement times. Data analysis will be performed using dedicated software. Additionally, obtained results will be coregistered with PET imaging performed to asses myelin content in a brain. Radiotracers dedicated to this measurements bind to the myelin basic protein (MBP) and they are used for Alzheimer’s disease diagnosis. The main goal of co-registration will be to create complementary images so that the entire procedure is more precise and reproducible than individual MRI and PET methods. This project is is carried out in close cooperation with Division of Radiology and Division of Nuclear Medicine in University Clinical Centre of Gdańsk.
Come back to Major areas of interests