Cedric Blanpain leads a research group studying the mechanisms that control the behaviour of stem cells, and the role of stem cells in cancer. He is Principal Investigator at the Interdisciplinary Research Institute (IRIBHM), Université Libre de Bruxelles (ULB), Belgium.
Cedric was a faculty member at this year's European Summer School on Stem Cells & Regenerative Medicine in Hydra, Greece. Between lectures, we talked to him about stem cells, skin cancers and making the switch from medicine to research.
You started out as a medical doctor. What made you move into research?
While I was a medical student, I spent some time doing short research projects and really enjoyed being in the lab. When I finished my medical degree, I decided to specialise in internal medicine. I spent two years as a doctor, doing the practical training I needed to specialise, but I already knew I wanted to end up in research. So I suspended my specialist medical training and did a PhD in the lab of Marc Parmentier in Brussels. I studied how the AIDS virus HIV enters cells, which was totally fascinating. Then I went back to the clinic to finish my training in internal medicine.
"I thought it was a really cool subject with tonnes of interesting questions to answer."
Switching between research and medical practice must have been tough…
It was extremely tough. When you’ve been in the lab for four years and then you have to go back to work in the intensive care unit or go out to a car accident, you don’t immediately feel comfortable. I took a lot of antacid pills to save me from ulcers at that time! But it was a really valuable thing to do.
Why did you choose to study stem cells?
In 2001 I finished my training in internal medicine and decided it was time to do something else. Stem cell biology was really just beginning at that time. I went to one of the first big stem cell conferences and loved the presentations. I thought it was a really cool subject with tonnes of interesting questions to answer. So I applied to lots of different laboratories for post doctoral research jobs. In the end, I went to work for Elaine Fuchs in the USA. She was studying skin stem cells. It was a very exciting time because not much was known yet about these cells. No-one could isolate them from other cells, so that was a big challenge I had to face with my colleagues in Elaine’s lab.
These days you’re leading a research group, trying to understand the role of stem cells in cancer.
How did that come about?
It was a great experience to work in Elaine’s lab and to live in the USA, to experience a different way of living. I loved New York, but when I started a family I wanted to come home to Belgium and decided to set up my own lab. Ever since I was a student, I had wanted to know the answer to a particular question: Exactly how do tumours get started? I wanted to understand how different cells might contribute to initiation and progression of cancer.
I had learned a lot about the skin whilst working in Elaine’s lab, so I decided to carry on working on skin. It’s a useful system to work with because we have the tools we need to look at different groups of cells in different parts of the skin. Skin cancer is also a very common cancer. A type of skin cancer called basal cell carcinoma is the most frequently occurring human cancer – there are almost a million new cases every year. It’s not usually life-threatening and can generally be treated with surgery, but we can learn a lot from it. In my lab, we also study another common skin cancer called squamous cell carcinoma. It can usually be treated in the skin, but it occurs in other organs too, and then it’s very nasty. So I decided to study these skin cancers and really try to understand them, then hopefully what I learnt could be applied to cancers in other parts of the body too.
What have you found out about skin cancers so far?
We use very precise genetic techniques to investigate how these cancers work. We can turn genes on or off in particular groups of cells and then look at what happens. We have used this method to find out more about exactly which cells start off the tumours.
In basal cell carcinoma, the cancer cells look like hair follicle cells. So it seemed logical to think that this cancer would arise from the stem cells of the hair follicles in the skin. We knew that a particular ‘oncogene’ causes normal cells to turn into cancer cells in basal cell carcinoma. We turned this gene on in the hair follicle stem cells in mice and looked to see what happened. We were extremely surprised to find that we never saw any tumours form under normal conditions in the body. It turned out that this cancer actually starts in the non-hairy part of the skin.
This is a very important finding because it tells us that the type of cell we find in the tumours cannot be used to predict the type of cell where the tumour originated. This is not what everyone had expected, but we see the same kind of thing for squamous cell carcinoma – the tumour cells look like cells from the interfollicular epidermis (non-hairy skin surface cells), but these tumours actually come from the hair follicle stem cells.
What are the big questions you’re trying to answer now?
Now we’re looking at exactly what happens from the first mutation in a cell’s genes when the tissue is still normal, right up to the point when the tissue becomes cancerous. We can turn the cancer-causing gene on at a very precise time and really follow exactly what happens in the cells at each step of the way during development of an invasive cancer. We want to answer questions like how does the tumour grow? What mutations happen in the genes and when do they happen? Are all the cells in a tumour involved in its growth? Or are certain cells the driving force?
There is a theory that some cancers might involve ‘cancer stem cells’. In other words, cells that can divide over and over to make copies of themselves, and can also make the other types of cells in a tumour. This type of cell would make a tumour grow and grow. These cancer stem cells might also be more resistant to therapies than the bulk of the cells in the tumour - that's one way to explain why patients might relapse after treatment. This idea of how cancer works could be true in some types of tumour and not in others. It’s important to know the answers to these questions if we want to treat cancers effectively. Can we treat certain cancers by turning off particular genes? Do we need to deal with different cancers in different ways?
So your work is a combination of basic science and medical research…
Yes, what we’re trying to do is a mix of developmental and stem cell biology, applied to tumour initiation and growth. That’s what I think is really interesting about this research, it’s at the frontier between developmental biology and cancer research. I’m interested in the ultimate goal of treating patients, but I also want to know the answers to the fundamental questions about how things work.
What do you hope you’ll have achieved in 5 years’ time?
I’d like to understand really precisely, at the molecular level, what drives things from the first initiation of a tumour to the development and growth of skin cancers. We still have a lot to learn about this, but we’re making progress.
"That's what I think is really interesting about this research, it's at the frontier between developmental biology and cancer research."
Further in the future I’d like to translate what we’ve learned in the skin to other tissues like the mammary glands, for example. Breast cancer is a huge problem and there are important similarities between certain cells in the skin and in the breast. Ultimately, I hope that our research can be translated into practice – to help improve the prognosis of cancer patients or develop new therapies.
What advice would you give to someone just starting out on a research career?
Find a very important question that has never been addressed, one that you really want to know the answer to. And always be optimistic – think, “if I have a very good idea or a very good question and I believe in that, then I can achieve something as long as I put in enough effort.”
What do you love doing when you’re not in the lab?
Playing with my kids. They’re three and five years old, so a really fun age. They’re really enthusiastic and energetic guys. I also love music, I’m passionate about jazz and love to go to jazz concerts. I spent 2 years trying to learn to play an instrument but it was just a catastrophe!
Find out more
More about Cedric Blanpain:
Related articles on EuroStemCell:
Information for cancer patients:
- European Cancer Patient Coalition
- Cancer Research UK
- Macmillan Cancer Support
- American Association for Cancer Research
Scientific reviews on skin stem cells and cancer:
- Epidermal homeostasis: a balancing act of stem cells in the skin, Blanpain C & Fuchs E, Nature Reviews Molecular and Cell Biology 2009; (3):207-17
- Epidermal stem cells of the skin, Blanpain C & Fuchs E, Annu Rev Cell Dev Biol. 2006; 22:339-73
- Therapautic applications of skin stem cells, Lapouge G & Blanpain C, Stem Book, Harvard Stem Cell Institute, 2008
- Cancer stem cells: models and concepts, Dalerba P, Cho RW, Clarke MF, Annu Rev Med. 2007; 58:267-84
- Heterogeneity in cancer: cancer stem cells versus clonal evolution, Shackleton M, Quintana E, Fearon ER, Morrison SJ, Cell 2009; 138(5):822-9