University of Eastern Finland (UEF) Main Research Lines

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1 University of Eastern Finland (UEF) Main Research Lines Asla Pitkänen, MD, PhD Epilepsy Research Laboratory A.I.Virtanen Institute for Molecular Sciences University of Eastern Finland Kuopio, Finland

2 Contents 1. UEF general overview 2. UEF Program in Neurosciences 3. UEF in SynaNET Examples of research projects

3 UEF 3 Cities Kuopio Joensuu - Savonlinna University Hospital Main Campus A.I.Virtanen Institute 130 km 160 km Kuopio

4 UEF students employees 3 cities (Kuopio, Joensuu, Savonlinna) 4 faculties the Philosophical Faculty the Faculty of Science and Forestry the Faculty of Health Sciences the Faculty of Social Sciences and Business Studies

5 UEF in Rankings

6 Contents 1. UEF general overview 2. UEF Program in Neurosciences 3. UEF in SynaNET Examples of research projects

7 UEF Top-level International Research Strategy Aerosols, Climate Change and Human Health 2. Cardiovascular and Metabolic Diseases 3. Forests, Global Change and Bioeconomy 4. Neurosciences 5. Borders, Mobilities and Cultural Encounters

8 Top-Level International Research Area NEUROSCIENCES

9 Research Focus and Goals To understand disease-specific and common molecular mechanisms underlying Alzheimer s disease (AD), traumatic brain injury (TBI), and posttraumatic epilepsy (PTE) to identify biomarkers and novel intervention approaches for their prevention and cure 9

10 Research Focus and Goals NEUROSCIENCES research area is a focused continuation of the UEF strategic Spearhead Program (UEF-Brain) Beyond state-of-the-art in research requires: Combination of unique datasets of molecular omics (genetics, transcriptomics, epigenetics, proteomics, and metabolomics) for integrated neurobioinformatics analyses Initiation of new collaborations, which will provide an access to the analysis of datasets on human TBI, normal pressure hydrocephalus and depression/anxiety Recruitment of experts to develop neurobioinformatics, big data analysis, imaging, neuroproteomics and metabolomics Development of infrastructures 10

11 Contents 1. UEF general overview 2. UEF Program in Neurosciences 3. UEF in SynaNET Examples of research projects

12 Olli Gröhn, PhD Professor of Biomedical NMR Project: In vivo imaging of damage -induced brain plasticity Objective to understand how microstructural and functional changes in a single node lead to changes in large scale network connectivity how that is associated with outcome in individual subjects. Major technologies EEG/fMRI with implanted electrodes and RFcoils fmri compatible brain stimulation Resting state fmri dynamic functional connectivity Diffusion Tensor MRI (DTI) PET (e.g. FDG and FEPPA for inflammation) 9.4 T PET MRI 9.4 T 7 T SPECT/CT

13 Annakaisa Haapasalo, PhD Associate Professor of Molecular Neurodegeneration Project: Mechanisms of synaptic dysfunction in frontotemporal dementia Objective To understand mechanisms of synaptic dysfunction and neurodegeneration in frontotemporal dementia (FTD), focus on hexanucleotide repeat expansion in the C9ORF72 gene (most common genetic cause of FTD; prevalent in Finnish patients) Major technologies Molecular biologicy, biochemistry, and cell biology Cultures of mouse primary neurons and co-cultures of neurons and microglial cells in vitro stress models ipsc-derived neurons from FTD patients Access to a well-characterized clinical FTD cohort (incl. clinical data and plasma samples) RNA foci DPR inclusions C9ORF72 repeat expansion-associated pathological hallmarks Neurons and astrocytes Neurons and microglial cells

14 Mikko Hiltunen, PhD Professor of Tissue and Cell Biology Head of the Medical Cell Biology Program Project: Identification of Alzheimer s disease (AD) -associated targets that affect synaptic structure Objective Delineation of AD-associated targets (identified in the genetic/proteomic studies) that affect 1) morphology, 2) size, and 3) total number of dendritic spines in primary hippocampal-microglial cocultures upon basal, excitatory stimulation and AD-associated stress conditions Major technologies RNAi/CRISPR-CAS/over-expression lentiviral transduction high-resolution confocal microscopy quantitative analysis of dendritic spines

15 Tarja Malm, PhD Associate Professor in Neuroinflammation Project: Microglia as modulators of synaptic functions Objectives: to understand impact of AD predisposing risk genes on microglial functions impact of microglial AD predisposing genetic background on neuronal functions and synaptic morphology mediators of neuron-microglia crosstalk Major technologies ipsc derived microglia developed in our lab 3D cultures primary murine cell culture models animal models of AD (5xFAD, APdE9); behavioral tests flow cytometric immunophenotyping cell sorting multiphoton imaging ipsc derived microglia Iba-1 GFAP 3D

16 Jussi Paananen, PhD Assistant Professor of Neurobioinformatics Project: Neuroscience drug and biomarker discovery using open science Objectives Integrate existing massive data repositories to create comprehensive database and data-analysis pipeline for drug and biomarker discovery Use the developed resources to discover and validate drugs and biomarkers Explore commercialization opportunities for the developed resources and methods Major technologies big data data science bioinformatics -omics cloud computing

17 Heikki Tanila, MD, PhD Professor in Molecular Neurosciences Project: Intracellular amyloid-β as the first step of Alzheimer neuropathology Objective to determine the functional role of intra- vs. extracellular Aβ, especially in neuronal hyperexcitability that is an early feature of Alzheimer s disease Major technologies transgenic mouse lines with intra- and extracellular amyloid deposion recording of local field potentials with multi-tip electrodes in freely moving mice behavioral testing viral-vector mediated gene transfer immunohistochemistry viral-vector mediated fluorescent labeling and confocal microscopy

18 Noora Niina Asla Pitkänen, MD, PhD, DSc Academy Professor Professor of Neurobiology Director of the UEF Program in Neurosciences Anssi Objective Niina Project: Molecular targets and biomarkers of post-traumatic epilepsy to identify systems biology-derived molecular targets as biomarkers and therapies in order to favorably modulate post-traumatic epileptogenesis Major technologies deep-phenotyping in vivo animal models of TBI and epilepsy powered preclinical study designs histology, behavioral analysis 9 d after TBI omics and bioinformatics tissue, plasma, exosomes severe TBI chronic high- and low-density video-eeg recordings mortality >30% in vivo and ex vivo MRI preclinical database collected using CDEs big data analysis approach collaboration with clinical colleagues with access to large TBI patient cohorts in Europe and USA