Om mig

A typical Swedish country-boy who took a long and winding path to become a researcher, through military service, IT-work as well as caring for the disabled, to finally end up here at Karolinska Institutet as a researcher in neuroinflammation. Always willing to critically question myself, as well as other people, and most importantly: scientific dogmas, which I believe are by nature always imperfect, and should always be improved and refined.

Forskningsbeskrivning

During my training as a PhD student I developed in vitro methods for assessing cellular activities and associated changes in phenotype with special focus on human microglia. My work as a post-doc allowed me to continue this pursuit more independently, also being a part of my work as a co-supervisor, guiding PhD-students to a successful thesis defense, and at the present developing my skills in the area further now as a main supervisor. I have applied these methods in studies that have resulted in several publications where I have been first, as well as last author. I am consequently familiar with the different aspects of inflammation in the brain with regard to glial activities, neurodegeneration, morphology, mediators, etc., the fundamental aspect of neurodegeneration is neuronal dysfunction and death. I have worked on improving existing methods for differentiating human neuronal cell lines to produce post-mitotic cells that resemble primary neurons, allowing an inexpensive and convenient way to perform experiments even in large-scale settings. I also have experience in working with human embryonic brain tissue, working in collaboration with Prof. E. Sundström (Karolinska Institutet), in an effort to characterize neuronal and glial cells derived thereof for use in in vitro models of neurodegeneration and neuroinflammation. It can therefore be said that my expertise lies in the use of in vitro methods to study neurodegenerative disorders in human cells, and I have applied this in studies on Alzheimer’s disease (AD).

My work also involves studies of clinical material from AD patients, including cerebrospinal fluid (CSF), blood samples and post-mortem brain tissue. In this work, I have focused on developing and improving assays for analysis of proteins and lipids in order to increase sensitivity, specificity and quality. In this part of my work I collaborate with Prof. Ann-Charlotte Granholm (Knoebel Institute for Healthy Aging, University of Denver, visiting professor, Karolinska Institutet), with whom I also share co-supervisorship. Furthermore, this work has made me become engaged in the work on the biobank at the Memory Clinic at the Karolinska Hospital where I am a part of the board reviewing applications from scientist interested in using material from the biobank, and work on improving the techniques and methods for sampling, handling and storing clinical material such as CSF.

Omega-3 (n-3) fatty acids (FAs) are believed to have beneficial effects in a variety of pathological conditions in various tissues including the brain. With regard to AD, the n-3 FA docosahexaenoic acid (DHA) has been receiving most interest due to its deficiency in the AD brain. I am part of the OmegAD group performing one of the first clinical trials in which n-3 FAs, including DHA, were given to AD patients (the OmegAD study). There was a positive effect of n-3 FAs on cognition compared to placebo in a subset of patients with mild AD, spurring subsequent studies in which n-3 FAs are included (Lipididiet, etc.). The OmegAD study have resulted in several publications in which I have been involved in analysis of the effects of n-3 supplementation on a number of molecular factors in CSF, blood and urine. I have applied the assays I developed in to show that n-3 FAs stimulate phagocytosis of Aß42 by human microglia.

The involvement of inflammation in the pathology of AD is well established, and the hypothesis that inflammation can be a driver of pathogenesis in AD is well known. However, the other, beneficial side of the double-edged sword of inflammation has not received the same attention with regard to AD. The resolution of inflammation and the associated process of healing and restoration are fairly new subjects of research. As a member of the research group of Prof. Marianne Schultzberg I have been part of a pioneering effort to characterize alterations in these mechanisms in AD, with the ultimate goal to find new treatments for this disease. We address these questions in studies on clinical material as well as in in vitro studies.

Delivering pharmaceuticals to target organs such as the brain is a challenge in the development of new treatments for disorders such as AD. Our collaborator Prof. M. Malkoch (Swedish Royal Institute of Technology) is a well-renowned researcher in drug-delivery systems where drugs are encapsulated in dendrimeric structural compounds, or even themselves constitute the dendrimeric structure, with the purpose of improving targeted drug delivery. Our role is to assess potential neurotoxic/trophic and immunomodulatory effects of the dendrimers, and prospectively, to produce pro-resolving treatments based on dendrimers. 

Pedagogiska meriter

Pedagogic experience and supervision

1990-91, work as substitute teacher in primary and high school

I have since 2004 contributed to the courses given by the NVS department by supervising laboratory courses and giving lectures on neuroinflammation for PhD-students, post-docs, physicians, as well as master students. I have also supervised many bachelor and master students in their project work.

Supervision of PhD-students

Former: Co-supervisor for Xiuzhe Wang (dissertation 2014) and Mingqin Zhu (dissertation 2015).

Current: Main supervisor for Ying Wang (registered 2017, halftime seminar 191216), and co-supervisor for Ceren Emre (registered 2016, halftime seminar 191007).

Utbildning

Magisterprogram Medicinsk Biologi, Linköping University, Linköping, Sweden

Doktorandutbildning, Karolinska Institutet, Stockholm, Sweden, disputation 2010-04-23

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