Interview with Karen English: where cell biology and immunology meet

6 Oct 2011
Emma Kemp

Karen is a post doctoral researcher in the lab of Prof. Kathryn Wood at the University of Oxford. Karen’s work contributes to the EC-funded project OptiStem. We caught up with Karen at the project’s 2011 annual meeting.





What is your research all about?
Mesenchymal stem cells (top) can differentiate into fat (adipogenesis - middle) and bone (osteogenesis - bottom) cell typesMesenchymal stem cells (top) can differentiate into fat (adipogenesis - middle) and bone (osteogenesis - bottom) cell typesMy research focuses on determining how the body’s immune system responds to stem cells, in particular mesenchymal stromal cells (MSCs). MSCs are a type of cell that can differentiate into a variety of other cells, including bone, cartilage and fat cells. MSCs are very interesting cells because they take part in repair processes in many different systems of the body. For me, their most interesting characteristic is their capacity to interfere with immune responses.

Some clinical trials are using MSCs in potential new treatments for graft versus host disease. This disease is a complication that can arise after a blood stem cell transplant, such as a bone marrow transplant, when the graft (the new bone marrow) attacks the body. There are very severe forms of this problem termed ‘steroid resistant’ graft versus host disease. Currently there are no drugs that actually help these patients and there is only a sixteen per cent survival rate within two years. These poor survival rates encouraged clinicians to use an experimental therapy like MSCs and they saw some very promising results. The cells seemed to encourage repair and stop inflammation, especially in the gut and liver (two of the main organs affected by this disease), but we have no idea how. My research focuses on investigating how these cells work in the body using animal models of disease.

My role in OptiStem is to use my knowledge of the immune response that occurs in MSC therapy to investigate a different type of cell therapy using cells called mesoangioblasts. Mesoangioblasts are a type of stem cell associated with the blood vessels. They have the capacity to differentiate into muscle cells. These mesoangioblasts are currently in very early stage clinical trials to treat patients with Duchenne muscular dystrophy, so it is important that we gain a better understanding of how the cells affect the immune system and how the immune system sees the cells.


"It’s the elephant in the room at every stem cell meeting; the immune response to cell therapies is one of the last problems to be tackled in the development of cell therapies"

Why is immunology important for stem cell therapies?
Regenerative medicine and cell therapy are really at the forefront of scientific research but to use new therapies successfully we’ll need a good understanding of how the immune system will respond to cells that are put into the body as part of a treatment. It’s definitely an underdeveloped niche. There are a number of researchers working on the regenerative properties of stem cells and other cell therapies. However, very few research teams actually consider the immune response to cell therapies and how we can control it. There is an array of immunosuppressive drugs, but these drugs have a substantial impact on patients’ lives. Unfortunately, the effect of these drugs is systemic, in other words they surpress the immune system of the whole body. Patients need to take the drugs over a long period of time and the drawbacks are increased risk of infection as well as a higher incidence of cancer. That’s why we’re interested in finding new ways to enable patients’ bodies to accept cell therapies without having to take drugs for the rest of their lives. In other words, to give patients what we call tolerance of the therapy. It’s the elephant in the room at every stem cell meeting, with many researchers fully aware that these cells are going to encounter the immune system but lacking a complete understanding of how to tackle these problems. In general, the immune response to cell therapies is one of the last problems to be tackled in the development of cell therapies.

How did you get into this kind of research?
Mesenchymal stem cells in cultureMesenchymal stem cells in cultureDuring my undergraduate degree  (Biology & Experimental Physics) at the National University of Ireland Maynooth, I did a six-week research project and I fell in love with immunology. Subsequently, I decided to do a Masters degree by research in immunology with the same supervisor – Dr. Mahon. My Masters research was focussed on signalling molecules called chemokines, which play important roles in asthma. This research project allowed me to develop a greater understanding of immunology. Towards the end of my Masters, an opportunity arose to do some research with REMEDI, a large regenerative medicine institute. Researchers at REMEDI focused on fundamental stem cell biology and the development of regenerative medicine therapies for diseases such as cardiovascular disease, diabetes mellitus and osteoarthritis. Dr. Mahon set up a collaboration with REMEDI to investigate the immune response to mesenchymal stem cells and this was the topic for my PhD. As much as I enjoyed working in immunology, the thought of applying my knowledge of immunology to stem cell therapies was very exciting.

Did your PhD supervisor have a large influence over your career path?
Oh huge, he did a lot for my career; his ability to encourage my interest in immunology was a significant factor in my decision to pursue a career in science. He knew more about the subject than I did of course, but it was wonderful to work with someone who was interested in teaching. The interaction we had and his ability to recognise my interest and encourage it was fantastic. That helped me flourish, so I had a very good relationship with my supervisor. There are a lot of very intelligent people in science and it’s wonderful to be part of that community.

How did you move your career forwards after your PhD?
First, I spent a year as a post doctoral researcher in the same lab as my PhD to finish off some of the work from my PhD. In the first six months I started to think about my career and where I should do my next post doc. I went to a couple of seminars on applying for grant money. One of them was about applying for an EU-sponsored Marie Curie Postdoctoral Fellowship. It was the middle of June and the deadline was the end of August. I approached the speaker at the end of the seminar and explained I had an idea for a research proposal but I wasn’t sure if my CV was good enough. So she looked at my CV, then said I should apply and that I was in with a chance.

Mesenchymal stem cell expressing green fluorescent protein, viewed under a fluorescent microscopeMesenchymal stem cell expressing green fluorescent protein, viewed under a fluorescent microscopeThen I had to decide who I was going to work with because for me I knew I had to work with someone who was going to push me in the right direction. I thought about who I knew and how I could diversify a little. After all, there were other people looking at similar things to do with the immune response to stem cells so I thought, ‘How can I make myself different?’ Prof. Kathryn Wood, a leader in the field of transplantation with an interest in developing stem cell therapies, immediately came to mind.  Prof. Wood was my external examiner for my PhD examination and she inspired me with her refreshing attitude to science. I approached Prof. Wood with some ideas for a proposal, we discussed it and she said “Why not? Even if we don’t get this first grant, it’s an ice breaker for something else.” We came up with the grant proposal and I got lots of people to read it for me. They all had very different ideas about how I could make it better, so I took those ideas and wrote the application and the grant got funded.

It must feel like a huge achievement to get your first grant.
Indeed it does. It appears that there are more opportunities available for early career stage post docs than, say, for someone with more than six years experience so it was really important to apply for personal fellowships as early as possible. I’m not sure what the statistics are but I think it’s about a 20–30% success rate for grant application and so it was both surprising and amazing to have my first grant application funded. A few weeks before you get the official yes or no, they give you an evaluation with feedback. I got 92% and I bounced in to my supervisor’s office saying ‘Look at my score’. He told me it was really good but it doesn’t guarantee that you’re going to get the grant and that I should stay calm. I got an email a few weeks later stating that I had been awarded the grant. I was elated, all the hard work had payed off.

"It’s very important to network and to communicate with fellow scientists to make the most of the opportunities out there"

It sounds like you have to be very proactive to get where you are. What advice would you give someone who is just starting out?
Life sciences research is brimming with some very exceptional people and you have to do everything that you can to stand out from the crowd. It’s very important to network and to communicate with fellow scientists to make the most of the opportunities out there. I would say, when you go to meetings always introduce yourself to principal investigators in your area of interest. Take them to your poster if you have one, or mention that you are giving a short talk and ask for feedback on your presentation skills and how your data came across. Meetings are an ideal environment to observe how researchers in other fields work and to think about how you can apply that to your own work. I guess be proactive, keep an open mind and don’t panic even when experiments are not working. Persevere and use your problem solving skills to get past the hurdle.

If we forced you to say something you don’t like about your job, what would it be?
The instability of not having a permanent job. Grants only last for a couple of years so you always need to be thinking about your next step. But there are not many jobs in which you get to ask questions about a specific problem that interests you, design experiments and find the answers,– that is pretty cool. How do cells get from one place to another? What signals does this process require? It’s fantastic to think you can find those answers out and hopefully contribute to our understanding of how to better treat patients along the way.

What do you want to achieve in the next ten years?
From a career point of view, ideally, I would like to have my own research group and to be a respected member of the translational medicine/cell therapy and regenerative medicine fields. In terms of science, it would be fantastic if we could figure out exactly how MSCs modulate the immune response in the body and use that knowledge to apply a more successful MSC therapy to patients.

And finally, what do you do when you aren’t in your lab coat?
I like to read, run or generally meet with friends and have a conversation that has nothing to do with work!

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Images by Karen English. Writing and editorial support by Samantha Le Sommer.

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Interview with Karen English: where cell biology and immunology

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