Interview with Miquel Àngel Peinado
Scientific Coordinator of the IMPPC
Q: This is a particularly exciting time for cancer research, can you tell us why?
In recent years a series of new techniques and knowledge about the genome have become available that provide opportunities that just few years ago were unthinkable. Until now cancer research involved just looking at specific points on the genome that were giving information about a small part of what was going on, but now we can approach the knowledge of the mechanisms of the disease from a global point of view and we are starting to get the whole picture.
Q: And this is producing more results?
Yes, we have a huge improvement in the tools we are using and this has had two benefits, an increase in quantity of data and also an increase in quality. The increase in quantity is generating a new problem; that we have more results but sometimes these results cannot be processed so they are not producing more knowledge. To deal with this huge amount of data we need to develop new tools to process them and convert them into knowledge. Results alone do not represent knowledge.
Q: So how has this change affected the focus of the work of your group?
In fact we have been working on cancer for a long time and our approach has always been to start from a series of primary tumors; samples obtained from cancer patients. We start each project by screening the tumor samples for new genetic and epigenetic alterations and trying to identify factors that can be correlated with the features of the tumor and that can be used to predict the behavior of the tumor in the patient. So for us, the availability of new tools hasn’t meant a critical change in the design of our experiments, but just the adaptation of the new methodologies to our objectives. In the past the study of one sample or a series of samples only generated a few markers and now with the new techniques we can generate thousands of markers. I would say that our evolution has been related to our capacity to process all this data plus, of course, the fact that in the last years we have moved from genetics to epigenetics.
Epigenetics is something I studied at the faculty, but at that time, very little was known and I would even say that it was even something “mysterious”. Our knowledge of the epigenetic processes has moved very fast in recent years and it now plays a very important role in most cancer investigations.
Q: Why is the epigenetic profile so important?
The epigenetic profile is set during development but is also affected by aging, by the environment, by what we eat and what we do; so in fact epigenetics is a kind of history of our life at cellular level. In a way, the genetic code represents a roadmap with all the possible routes from one point to another. Once the trip is started any point in the route has a past that allowed the cells to reach this point and a limited number of ways to continue, perhaps just one. Therefore epigenetics defines the part of the map the cell is using and when and how it is using it. By looking at our epigenetic profile we should be able to read it and know our biological history in the same way. The combination of genetics and epigenetics is going to be critical to define the risks an individual has of developing different diseases.
Q: And this is a basis for predictive medicine?
Yes, in the future we will have the ability to read the epigenetic code of our cells and together with their genetic profile and all the other factors, for example environmental, that we know of about an individual we will be able determine which diseases have more chances of occurring in that person. This of course means that the appropriate actions can be taken earlier.
Q: Can you comment on the biological mechanisms you are studying at the moment?
Currently our main interests are the epigenetic profiles of cancer cells, how they are defined during the stages of the cancer process and we are especially interested in studying the initial steps, when cells are not yet malignant. In our latest studies we have seen that the epigenetic profiles of cancer cells are very similar to those found in embryonic stem cells so this has many important implications. The first is that cancer cells probably arise from stem cells so they have many of the features of stem cells such as the plasticity to adapt to different situations and the capacity to proliferate. This also has implications for treatment because these cells will respond very differently from differentiated cells to many of the treatments we have today and many of the possible treatments of the future. I think that this new picture of the cancer cells sets a new landmark in how we have to face future therapies.
Q: Where would you put your group on the gradient from pure research to applied research, which of course leads to clinical research?
Well, as I said before, we have always using samples from patients as a starting point. We obtain the samples from patients who have passed through the operating theatre to have tumors removed. We also investigate the normal tissue from these individuals. If you ask me about that gradient I would say that we start from the patients and work backwards. What we try to do is identify new alterations in these tumors from the patients, once we have identified alterations at genetic and epigenetic level we look for the mechanism. If we are able to identify new alterations we want to discover the mechanisms behind them. So at the end of our projects we need to go back to do more pure research.
Q: And this information is then fed forward again?
Exactly, once you know the mechanisms you can either design new tools for diagnostic purposes or you can design or propose new treatments for these mechanisms that are working in a different way in cancer cells.
Q: And the objective of the IMPPC is to include people working at all these different stages?
Indeed, eventually we will carry out work with implications at all these levels from very pure research to future diagnostics and treatments. At the moment priority will be given to groups that are trying to identify the factors that are related to the disease and the factors that can be targeted as markers of disease or as therapeutic targets. But through adding new groups and through collaborations we are going to extend our activities in both directions. On one hand what we need to do is to maintain the relationship with the groups at the hospital and the physicians who are treating the patients and doing the diagnosis of the disease. On the other hand in order to get a complete view of the process, we need to have people working on basic research so we can better understand the mechanisms that are behind these diseases.
Q: Who are the strategic partners working with the Institute?
Obviously the hospital is absolutely necessary as it is the source of the samples. But this it is not just a passive source but a vital partner providing the information we need about the patients; their evolution and the specific features of their disease so we need to collaborate with the oncologists, the pathologists, the people involved in therapy and with the epidemiologists. There are different disciplines that we need to interact with in order to get the full picture. Within the hospital the Catalan Institute of Oncology (ICO) is the body that takes care of oncology patients. We are setting up the ICO-IMPPC Joint Program for Molecular Diagnostics of Hereditary Cancer. This is an area where Predictive and Personalized medicine has advanced considerably. In those cases where there is an increased familiar risk of cancer we need to identify the individuals who are a higher risk and for this it is essential to discover the molecular alterations and epigenetic profiles that will help identify those individuals.
Q: We often hear that we want to attract the best researchers. For you, what marks out the best researchers?
Today it is difficult to define what the ideal profile for a researcher is, because we need to do so many different things and the ideal researcher probably doesn’t exist, or at least they are extremely scarce. Investigators need to be creative; we need to have the capacity to organize teams and budgets so we need management skills. To carry out the actual research you need to learn many different techniques and often new skills entirely. This is the reason that many of the more important studies today are done by multidisciplinary groups. They require a lot of people; people good at the technical level in the different areas, people good at management and people good at coordinating.
Q: And this is why you need multidisciplinary groups at the IMPPC?
More than multidisciplinary groups we need groups with different expertise; it is the work that is multidisciplinary. So in my own group we have elected to have bioinformaticians within our group as for our current studies we need to use bioinformatics and most of the data we are generating needs to be analyzed within the group and not externally so we put a lot of effort into this. Other studies involve sharing technically different parts of the work between groups. Some of the funding awards reflect this, for example European research grants which are often awarded to projects involving many groups and in different countries. Certainly today’s researchers need to be flexible and to adapt to new challenges quickly.
Q: You’ve worked in cancer research for some years, how would you describe the research climate in Barcelona at the moment?
Well, if we look at the past I think we have to be very optimistic because the situation is so much better than it was ten or fifteen years ago, even much better than it was five years ago. But it is not a time to relax, we are very far from the ideal situation and still far from the situation in the UK, France or other European countries for example. We need to create a climate that will attract good researchers to come here but once they are here we need to have the resources to guarantee that they can do their work effectively.
Q: Is there room for so many centers In Barcelona?
I certainly think we still have a need for more centers. However, it is true that there is no point in simply opening new centers, they need to be consolidated and there needs to be some guarantee that work can continue. If you look at other areas in the world known for biomedicine you will find clusters of world class research centers such as in San Diego Bay in California where you have: the Scripps Institute, the Salk institute, the Burnham Institute for Medical Research and the University of California (UCSD). Their proximity guarantees an atmosphere of intense scientific activity, a good job market and a supply of good students. In terms of budget the Barcelona Biomedical cluster still has long way to go compared with clusters in other countries.
Q: How do you see the IMPPC contributing to training and education?
You cannot do scientific research without constant training. Most of the work carried out is done by people at different stages of their education whether they are PhD students at the start of their careers or investigators on their first or second post-doctoral contract. A researcher takes years to complete his or her training which will involve working in different labs and different countries. The IMPPC already has many doctoral students working and will expand its educational activities to include masters courses in conjunction with the Autonomous University of Barcelona (UAB) which also has a teaching unit on the same site as the University Hospital Germans Trias i Pujol and the IMPPC. Education and research are intimately linked.
Q: What is your advice to somebody thinking about a career in biomedical research?
Well, it is very positive. It is the right time and Barcelona is the right place at the moment, and hopefully in coming years!