PAN’THER FCE in Rouen, France
About Olivier Boyer, MD, PhD
Career path
1. How did you first get involved in immunology?
In France, medicine and science, these studies are mostly separate pathways and I wanted to mix the two and have the opportunity to follow dual programs, both in the School of Medicine and in the Faculty of Sciences in Paris. This led me to deepen my knowledge in basic science more than medical students generally do and that was fantastic. Medical classes in immunology were quite practical and relatively disease-oriented with little space for pathophysiology. In contrast, studying basic immunology at the Faculty of Sciences was immediately fascinating to me. I met immunologists who were inspiring to me, such as Michel Seman, who introduced me to the main immunological concepts, such as self and non-self. Then I joined the Pasteur Institute for a Master’s Program in Immunology with a training in the lab of Antonio Coutinho. At that time, research on suppressor T cells had been discontinued, not to say banned. Yet, we believed that clonal deletion of autoactive T cells could not be the sole explanation for tolerance to self. It may seem straightforward nowadays that Tregs have been rediscovered, but it was not a popular idea at the time. Then I completed my medical studies in immunology and joined the lab of David Katzmann in Pitié-Salpetrière Hospital in Paris for my PhD where I was working on gene regulation in T cells and applying this to suicide gene approaches for the treatment of Graft Versus Host disease.
2. Tell us about the research you’re most proud of.
It’s a difficult question because I’ve explored very different fields in immunology such as tolerance, autoimmune diseases, Graft Versus Host Disease, cell and gene therapy. Early on, I had been quite proud of my work during my PhD, where we characterized regulatory sequences of the human cd4 gene, which helped not only to help better understand gene expression during T cell differentiation, but also provided tools for expressing therapeutic genes in transgenic mice.
A more recent example of something that I find rewarding, because of its translational character, is that we recently elucidated part of the pathology of the so-called immune-mediated necrotizing myopathy. In the course of this research, we happened to develop several immunoassays to detect autoantibodies in myositis. Myositis are a group of severe autoimmune diseases of the muscle that may lead to a bedridden state and death. Some myositis mimic muscular dystrophy and diagnosis was challenging when no genetic mutation was found. So before commercial assays were available, our tests allowed to detect autoantibodies that ascribed the disease to an autoimmune rather than genetic origin. This offered the possibility of treatment. From this, we developed the first mouse model of this disease by transferring patients’ autoantibodies into mice. And now we can test drug candidates targeting immunoglobulins or complement. That is very rewarding.
3. What is the most important trait a researcher should possess and why?
A researcher should never be discouraged. But this being said, perseverance goes with an open mind and curiosity, so you don’t remain stuck on the wrong idea.
4. What is the biggest lesson you’ve learned?
I was once told and I learned that failure may be the first step toward success. And I have to say that has been my personal motto since.
5. What advice would you give to young researchers just starting out in the field?
I would tell them that teamwork is the heart of research. But yet you have to be the pacemaker of this heart. You will find many people ready to help you, but it doesn’t necessarily mean that they’ll have the time to do so. So, you have to closely monitor the advancement of your own research program and if people around you don’t deliver, well then: do it yourself!
6. Describe your average workday.
Oh, I don’t think I ever lived anything like a typical workday. Every day is very different and it’s a chance. I feel blessed by the variety of the activities I get to do every day. Maybe it comes from the fact that I’m a director of both a research laboratory and of a department of immunology in a university hospital that are located in the same building. Therefore, I constantly switch from one to the other—between hospital duties and research. I have a lot of meetings, which are now rendered difficult by COVID, of course. I have to go through a lot of management that has taken me away from the bench. I also teach immunology and gene therapy at the School of Medicine and the Faculty of Sciences. On top of that, I always try to keep time for collective and international activities, such as my commitment to IUIS, Immunopaedia, and, of course, FOCIS.
Work with FOCIS and FCE's
8. Switching gears, how did you first get involved with FOCIS?
I first got involved by attending one of the FOCIS meetings. It was in 2011 in Washington. I thought it was the perfect congress format with top-level science, outstanding speakers, focus on human interventional immunology (which is my main interest), opportunities for networking and also an excellent organization.
9. How do you think FOCIS has changed your world?
It has increased the visibility of my research at the international level. FOCIS has allowed me to get in touch with colleagues, some of whom I am now collaborating with. I feel that there is a FOCIS spirit and I like it. Over the years I have become more and more involved in FOCIS. I have advocated FOCIS membership to my national society, the French Society of Immunology, which became a FOCIS member society in 2013. Then I served twice on the FOCIS Steering Committee. I organized last year’s member society joint session with ALAI, which is the Latin American Association of Immunology. This was also last year that we became a FOCIS Center of Excellence (FCE) and this year that I joined the FCE Committee. FOCIS indeed changed my world!
10. If your colleague asked you why they should join FOCIS, what would you tell them?
I wouldn’t wait until they asked me. I would rather go and tell them before they ask. They should definitely join FOCIS because FOCIS organizes the best congress of immunology ever. Seriously. Not only is the quality excellent, but the possibilities of interacting with people are like nowhere else for a general immunology meeting. It’s true for the juniors. It’s also true for the seniors. I may add that besides attending the Annual meeting, being an individual FOCIS member, creates some opportunities, especially for some young immunologists, such as travel grants, discounts on registration fees for the annual meeting and courses.
11. Tell us about the research you’re doing.
The research of our FCE, which is named PAn’THER, for pathophysiology, autoimmunity and biotherapy, focuses on the immunopathology and the treatment of autoimmune diseases. We study autoimmunity and immune regulation in physiological and pathological context through murine models and clinical studies. We have two main diseases of interest: one is myositis, which I talked about earlier, that targets the muscle, and the other is pemphigus, that targets the skin. Our research aims at better understanding the mechanisms involved in these diseases and also at developing diagnosis tools and implementing innovative therapeutic approaches. For instance, I set up a cell and gene therapy facility in my hospital which produces clinical grade cells for clinical trials.
12. What is the vision/your dream goal of your FCE? What are the specific goals as the FCE Director?
The general goal of our FCE is to do more and more valuable science, to see it translated in humans though clinical trials and to investigate back on the bench some questions that arise from the results of these clinical trials. We also want to keep training a future generation of researchers and practitioners in clinical immunology, notably dermatologists, rheumatologists, hematologists and people working in clinical laboratories for diagnosis. As an FCE Director, and together with my colleague and Co-Director, Catarina Abad, we also want to keep on raising the economic and financial resources that are necessary for developing our activities. For this, putting people to work together and seeking synergies between investigators with different backgrounds is what an FCE Director like me should try to do, I guess.
13. What are your biggest challenges?
The challenge for me, as for any scientist, is to make a significant contribution to science or medicine. For this, you have to sort between the new ideas that constantly come to your mind and determine which ones deserve to be pursued, given your resources. For instance, one of our specific challenges at the moment is to produce clinical grade CAR-T cells for therapeutic use in cancer. More than 100 clinical trials are ongoing in the US and China but France is clearly lagging behind. And I regret that no patient has been treated to date with CAR-T cells produced in an academic setting in this country. Since our cell and gene therapy facility has the experience and the certifications for producing clinical grade cells such as myoblasts, we have been working on producing CAR-T cells for more than one year and we’re getting there now. The challenge will be to complete the clinical trials we have in mind and that are under evaluation for funding currently, and ultimately to make this available to patients.
14. Why did you apply to be an FCE?
Because FOCIS is a prestigious organization and receiving the FCE label was really an honor. I wanted to have this recognition for our center because I believed that it could further motivate the people around me to increase their ambition in science. Also, there is a leverage effect that it creates for getting funding, and the input that we have from our scientific advisory committee is very motivating and helpful. I knew that becoming an FCE would create opportunities for training for our fellow students through travel scholarships. One of them participated in the FOCIS course in San Diego last year just before the lockdown. It was her first scientific experience abroad! I’m happy that we’ll bring seven of my colleagues to take part in the virtual FOCIS meeting by the end of the month.
15. Talk a bit about how your community outreach programs have helped to educate the public.
I think that community and science outreach toward the general public is very important. As an example, we have a once a year lab visit from patients and donors to patient’s association to tell them about the diseases we’re working on. People really want to understand why they are sick and what’s going on in research to help them. What I really find rewarding is that it is always a two-way experience. We get closer to the reality of what people need and it’s a booster to continue our effort. Dealing with the public is a very enriching experience. Also, we have visits of our laboratories from students at all levels from primary school to university. These visits are very important to open the mind of the young generation to what research is and what a research career may be. Imagining that we might have inspired some future researchers is good.
16. Talk about how the clinical trials for rituximab for pemphigus are proceeding.
Our previous clinical trials, led by our dermatologist Pascal Joly, have shown that rituximab used as a first line drug in pemphigus, provides a clear benefit as compared to standard care. This has led to a new indication of rituximab by the FDA and the European Drug Agency. Patients have now been followed up for seven years and we’ve seen that the long-term relapse rate is really very low. Now we turn to investigate the mechanisms of this spectacular effect of rituximab by analyzing autoreactive T cells at the single cell level and autoantigen-specific follicular helper T cells. In parallel, we are looking for biomarkers that could predict the low risk of relapse, and we try to understand why a few patients maintain complete remission despite the presence of autoantibodies. We are also evaluating the use of rituximab in other forms of autoimmune bullous diseases such as so-called mucous membrane pemphigoid in a randomized clinical trial versus cyclophosphamide.
17. Talk about the creation of a biorepository and study of national/international cohorts of myositis patients.
This has been first accomplished thanks to our long-term collaboration with the clinical team of Olivier Benveniste in Paris. I used to work there. We have conducted many translational studies together and for instance, we recently demonstrated that autoantibodies found in a majority of patients with immune-mediated necrotizing myopathy are directly pathogenic in a mouse model. This had required using plasma from patients who underwent plasma exchanges so as to extract their IgG and show that they transfer disease in mice. Now we are investigating the role of different complement-targeted therapies using this very translational mouse model. We collected sera as well from patients with other forms of myositis in different clinical trials. For instance, we recently observed that having autoantibodies of certain isotypes is highly predictive of a risk of cancer in patients with dermatomyositis. And thanks to a large international effort of developing biorepositories in different countries, we are currently trying to confirm this observation with a larger sample size and a more diverse panel of patients, and try to shed light on the link between autoimmunity and cancer.
18. Talk about your teaching program and what it has accomplished.
First, in the lab we provide training to undergraduate, graduate and medical students and we currently mentor nine PhD students. We are quite involved in teaching since several members of our FCE, including myself, are faculty members of the School of Medicine and Pharmacy as well as the Faculty of Sciences of our university. We teach courses in immunology and cell and gene therapy. Thanks to the pharmacists who take part in our FCE, we have just set up a new two-year Master’s Program in Biotherapy and Industrialization in Biotechnology. We organize symposiums on different topics of interest to our FCE such as oncotherapy. As you can imagine, we had several plans for future symposiums and participation in international courses, but unfortunately, due to the current health situation, these have been put on hold. To keep on the international aspect, I am a member of the Education Committee of IUIS, which is the International Union of Immunological Societies. I was invited to give lectures at the Advanced Immunology Course of the IUIS in India in October last year and also we’re happy to actively contribute to Immunopaedia which provides online teaching resources, notably for the IUIS courses. I hope everyone will enjoy the virtual FOCIS meeting but also hope we can soon be able to meet face to face to exchange and do more exciting science together, because FOCIS is really the place for that!