Where did you complete your training?
I completed my undergraduate degrees at the Biochemistry and Bioengineering department of the École normale supérieure Paris-Saclay (ENS) in France. The school is entirely dedicated to training future educators and researchers. The ENS gives students the opportunity to spend a year or two abroad, and I was lucky to have my first research experience in the laboratory of Rudolph Tanzi at Massachusetts General Hospital in Boston. This is where I cemented my interest in neurodegenerative diseases such as Alzheimer’s disease. I then went to the California Institute of Technology, in Pasadena, California, to pursue my doctorate in neurobiology with a scientific hero of mine, the late Seymour Benzer. Following the advent of induced pluripotent stem cell technology, I headed to the Whitehead Institute in Cambridge, Mass., for my post-doctoral work in the laboratory of Rudolf Jaenisch.
Tell us about your research.
My primary interest is the etiology of neural and glial degeneration, particularly when there is an age-related aspect to it. Eventually, all central nervous system diseases manifest themselves outwardly in neuronal dysfunction, and motor, sensory or cognitive deficits for the patient. But we now appreciate how the problem often starts in glia, the non-electrical cells of the brain. Those constitute more than half of the cells of an adult human brain, and they are not merely a structural scaffold, or a set of insulating elements. One subpopulation of glia are cousins of some white blood cells, macrophages: they are known as microglia. We managed to generate these immune cells from patient skin, via pluripotent stem cells, in the dish. Microglia owe their identity to their residence in the brain, and their biology is linked to the surrounding presence of all the other cells of the brain. For that reason, we devised 3D cultures trying to replicate the tissue-like environment, allowing the study of patient microglia as they interact with neurons and other glial cells. These cells are still very mysterious, but circumstancial evidence is mounting about their involvement in a plethora of disorders. We have a functional platform to test how modulation of their activity (be it by mutations, protein aggregates or viruses) intersects with development, maturation, and degeneration of neural networks.
Why did you decide to come to Toronto?
Living in a new city and a new country is an exciting prospect. The University of Toronto is extremely well respected in the stem cell community, with pioneers ever since James Till and Ernest McCulloch. The Hospital for Sick Children is a powerhouse of research and clinical development in pediatric medicine. I have a particular interest, since my early days working with iPS cells, in a disease called adrenoleukodystrophy, which is a devastating disorder often presenting in childhood. It is also one of the few diseases that is already benefiting from fringe therapies using autologous stem cell transplants and gene therapy combinations. And yet, more needs to be done and understood. Toronto is a perfect place to continue this work, with direct clinical input, and hopefully therapeutic outputs down the line. I felt wonderfully welcomed from the first visit on. As a French citizen, I also liked the idea of coming to country with an old mix of cultures, and bilingual signs in the airport!
What are you most looking forward to about joining the Medicine by Design community?
The existence of Medicine by Design was a strong factor in choosing Toronto. I was lucky to train at institutions where interdisciplinarity has been the modus operandi for a long time, with very strong basic biological science emerging from cross-talks with so-called harder sciences. All those places also had in common a remarkable engineering tradition: I love to understand how things work, and then replicate what nature does to eventually go beyond. Medicine by Design is a community that understands that interdisciplinarity is key to leveraging the expertise of everyone on campus, to maximize benefits to humanity, patients in particular. A lot of fundamental science goes into laying out the groundwork for the greatest biomedical discoveries, and having a climate that promotes transitions is invaluable. My work on “human-in-a-dish” approaches will be very much at home here.
What is one thing that people might not know about you from your CV?
I love to play the piano and sing too loudly. My future colleagues might hear random renditions of Elton John’s Tiny Dancer, or Jean-Jacques Goldman on the French side, late at night in the corridors of SickKids, once I figure out where the best acoustics are. Born and raised in the Alps, I am a winter sports enthusiast: if and when I find the time, I will be visiting the legendary ski resorts Canada has to offer.
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