Research Rendezvous: an interview with Mikael Karlsson

Congratulations on your new appointment to Proffesor of Immunology! Could you tell us a little about your research background?

I studied at Uppsala University where I did my masters degree, and at the same time worked in the Immunology Lab of Rikard Holmdahl before he moved to Lund. My project, amongst other things, was to sequence mouse MHC class II in connection to autoimmune disease. This project really helped to spawn my interest in Immunology!

After Rikard Holmdahl moved to Lund I worked with Birgitta Hayman in the Rudbeck laboratory in Uppsala for my PhD. I stayed there for four years and studied feedback regulation of antibodies. She had model systems to see how antibodies can block immune responses. This is used by clinicians for mothers with Rh negative blood types who give birth to Rh positiv children , so they don’t get immunized against RH factors. Its used in Rh profylaxis although still to this day we dont know how it works. My project was to test one or two hypotheses. Some of the mice I used for this project came from Rockerfeller University in New York, which was later one of the places I applied to for a Post Doc.

Between 2000-2005 I worked as a Post Doc at Rockerfeller University in the lab of Jeffrey Ravetch. I continued working with antibodies (FC receptors ) and also started to appreciate that there are different B-Cell subtypes in the immune system and that they inhabit different niches These B-cells are very different from each other– they don’t circulate in a similar manner, and there are for example different subtypes in the lungs and spleen. Doing these studies at Rockerfeller made me decide that this research was what I wanted to focus on when I returned to Sweden. The question then was: how are these subtypes of B-Cells regulated and how are they recruited in an immune response? In the beginning I studied this in inflammatory diseases, such as allergies or autoimmunity (SLE) to see if any distinct population of B cells were prone to give rise to disease related antibodies.

I moved to the Department of Medicine, Solna to build a group and carry on with this research and started to work on how B-Cells interact with macrophages. We looked at these interactions and how they regulate each other and because of this research I became interested in atherosclerosis. The connection between SLE and atherosclerosis is apperent in patients that often suffer from both diseases. This interest led to a collaboration with Prof. Göran Hansson that is still ongoing today. Along the way, Lisa Westerberg (moving back to Sweden from Boston) joined the lab and we have shared space and collaborated since then.

Could you describe you current research project at MTC?

At some point we outgrew the Department of Medicine, and I was approached by MTC. The recruitment was for both my group and Lisa Westerbergs group and our research has continued with autoimmunity models in connection with atherosclerosis. Through working on these specialised machrophage subtypes we also found that some of the phenotypes of cells could be found in Tumour stroma, which are comprised of different cell types that support tumour grown. It's a sort of controlled inflammatory response and a lot of these cells are macrophages that get attracted and instructed by the tumour to support it in terms of vascularization, processes that stop immune reactions e.t.c. Having worked on macrophages in B-cell subtypes in spleens and lymph nodes we started looking at what these macrophages are doing in tumour cells. This has grown and at the moment half the lab is involved in tumour related research.

We have already discovered one antibody to target these macrophages to help treat cancer. This is a collaboration with Rockerfeller University and a number of labs here at Karolinska Institutet, and there is also interest from the biotech industry to develop this immunotherapy further.

What are your plans for the future and how do you feel about being at MTC?

It has been a really good move to MTC for our group and we already have collaborations with Gunilla Karlsson Hedestam, Benedict Chambers, Klas Kärre and Jonas Fuxe at the department. We like the vibe at MTC, there is a direct connection to the HR department, people are friendly and its easy to talk to people. There are good facilities for doing the research that interest us especially. Since I recently moved I have mixed feelings moving into Biomedicum in some ways, as I feel the balance is good here, but I hope it will be good there also. As with all moves imagine there will be a start up period in Biomedicum before the move shows its true value.

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Mikael Karlsson appointed Professor of Immunology

Mikael