Tarja Malm, PhD

Associate professor in Neuroinflammation

Department of Neurobiology, A.I.Virtanen Institute for Molecular Sciences, University of Eastern Finland

I. The research group.

The goal of the Neuroinflammation research group is to understand inflammatory cell functions, especially those of microglia and astrocytes and mechanisms and mediators of inflammatory reactions in neurodegenerative diseases, especially Alzheimer’s disease and stroke. We use interdiciplinary approaches to find novel targets for modulation of neuroinflammation for the disease benefit.

Specifically, our research is focused:

 - To unravel disease specific and common mechanisms of neuroinflammation
 - To identify the secreted cellular mediators, such as exosomes that contribute to neuroinflammation
 - To identify how neuroinflammation is regulated by non-conding RNAs
 - To identify novel treatment strategies to modulate neuroinflammation for CNS benefit.

We were the first to demonstrate that bone marrow derived cells infiltrate into Alzheimer’s disease transgenic mouse brain and take part in neuroinflammatory reactions (Malm et al., Neurobiology of Disease, 2005). We also have recently shown that modulation of microglial activation by peroxisome proliferator activator delta (PPARdelta) agonist leads to rapid clearance of beta-amyloid from the brain of Alzheimer’s disease transgenic mice (Malm et al., J Neuroinflammation 2015)


II. Participation in the MADGIC project

Our task in the JPND MADGIC project is to generate humanized chimeric mouse models of AD. In addition, our aim is to set-up a platform to uncover cell and non-cell autonomous mechanisms of AD in vitro and in vivo. During the project we have developed a protocol for differentiation of microglia-like cells from the iPSCs. Our aim is to characterize astrocyte and microglia phenotypes and their contribution to AD- linked neuronal phenotype in fAD and sAD. We will pay specific attention to the impact of glia to synaptic alterations under pathological conditions with the aim to provide better understanding of inflammation in AD, eventually contributing to the new target identification.
The cellular models generated from fAD and sAD patients and humanized chimeric animals will be used to study repurposing of EMEA/FDA approved drugs and to determine the neuroprotective role of viral gene therapy-based systems.

III. Key publications relevant for the project

1. Savage et al. (2015), Nuclear receptors license phagocytosis by trem2+ myeloid cells in mouse models of Alzheimer's disease. J Neuroscience. 35(16)6532-43
2. Malm T et al. (2015) Activation of the nuclear receptor PPARδ is neuroprotective in a transgenic mouse model of Alzheimer's disease through inhibition of inflammation. J Neuroinflammation, Jan 16; 12:7
3. Karkkainen V, et al., (2012). Brain environment and Alzheimer's disease mutations affect the survival, migration and differentiation of neural progenitor cells. Curr Alzheimer Res.9:1030-42
4. Pomeshchik et al. (2014) Transplanted human iPSC-derived neural progenitor cells do not promote functional recovery of pharmacologically immunosuppressed mice with contusion spinal cord injury. Cell Transplantation, Sep 8
5. Kanninen K et al, (2009) Intrahippocampal injection of a lentiviral vector expressing Nrf2 improves spatial learning in a mouse model of Alzheimer's disease. Proc Natl Acad Sci U S A. 106(38):16505-10