涩里番
This conversation with D2R Training Program Officer, Anthony Van Kessel, has been edited for length and clarity.
Hi Michael, I am glad to be chatting with you today. You are supervised by Professor Ciriaco Piccirillo at the RI-MUHC and are a D2R Master鈥檚 Scholar. What first made you interested in D2R?
I was a newcomer to 涩里番 in terms of my academic career, starting my Master鈥檚 in Fall 2024. Coming from the University of Toronto, I was unaware of what resources were available for different areas of biomedical research at 涩里番. I found D2R and was excited to see this translational community that is aligned with the work that I am currently doing for my thesis.
What research experience did you have before coming to 涩里番?
My undergrad was in Immunology, but the research I did was very far from my own field. I found myself developing DNA and RNA aptamer-based sensors for detecting transcripts that are disease-related and synthetic sequences for industrial applications. Coming from this more bioengineering-heavy background, I came to 涩里番 to do more fundamental research. So it鈥檚 nice to be part of D2R, as the work being done by trainees in the community relates to what I鈥檓 exploring now.
I鈥檓 glad that you found D2R 鈥� what have you enjoyed about the trainings so far?
I think there are some cool opportunities to learn about things that you would not learn in the classroom. What really comes to mind is the training with CASTL, which walked us through the biomanufacturing of lipid nanoparticles. I felt like a kid going to the museum for the first time. They brought in all these things you just hear about, but you never really see this equipment that is used in biomanufacturing facilities.
I鈥檓 glad you enjoyed the hands-on trainings, because that鈥檚 something we are looking to build more of going forward! Now back to your studies 鈥� you said you moved to more fundamental research for your Master鈥檚?
Yes, coming from experience on projects where the goal is to optimize or set up a new protocol, it has been good to be in an environment that emphasizes how to properly think like a biologist. While I undergo this mindset shift in how I think about research, from bioengineer to biologist, being a part of D2R keeps me in the loop with the work being done in 涩里番 on the translational side.
Have you thought about what you want to do after your Master鈥檚?
Yes, my next step will be working in the startup space. My goal is to gain work experience before returning to academia. I say that in a bittersweet tone because I will miss my time in this lab, in the Microbiology and Immunology community, and in D2R.
What do you think working in academic research spaces has taught you?
Academic research has taught me that having genuine discussions with lab mates and coming up with cool new research ideas is an experience best done with an open mind. Moving here has taught me how every lab is kind of its own ecosystem. When you change environments, it really is important to step forward with humility in the spirit of soaking up as much information as possible. You will mess up; you will make mistakes. What matters is that you know when to say, 鈥淚 need help鈥�. This approach not only allowed me to grow as a scientist but also become a more reliable member of the team.
What is the specific project you are working on?
So, I'll start with the biological question. The overall premise is that there are a set of autoimmune diseases that involve regulatory T-cells (Treg), called Tregopathies. Though these are inborn diseases with a distinct genetic cause, their symptoms can present only a few months to a year after birth. I work on a Tregopathy that's considered the apex of this family, known as IPEX syndrome (Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked). This rare disease originates from mutations in a single gene, FOXP3. Mutations in this gene can result in the loss of your body's defence against autoimmunity through the loss of regulatory T-cells.
What do regulatory T-cells normally do?
Regulatory T-cells provide routine surveillance against autoimmunity, reigning in overreactive T-cell responses through a variety of inhibitory mechanisms. When you lose this activity of Treg cells through, for example, a loss of FOXP3 function, autoimmunity can develop.
What are you working on specifically?
Our lab set out to make an in vitro organoid model of the human thymus which can support T-cell development, including Treg cells. While the field has many mouse models to study this process, we lack reliable model systems for studying Treg cell development in human thymus. Our lab has produced an artificial thymic organoid system that allows us to differentiate primary donor blood-derived hematopoietic stem cells into various T cell populations, including Treg cells.
My approach is to implement this process using an induced pluripotent stem cell (iPSC) line as a standardized input, so that we can bypass current challenges specific to donor-derived hematopoietic stem cells such as donor-donor variability. Furthermore, using iPSCs we can integrate the IPEX-associated FOXP3 mutations to study how Treg development is affected in the disease.
Someone will pick up this project from you. Thinking through a D2R lens, how could this project one day advance D2R鈥檚 mission of developing RNA therapeutics?
In the rare disease space, there is always the need to find new targets and new strategies to reduce burden on the patient. On that note, this workflow could be used to evaluate therapeutics in the future. For example, these edited iPSC-derived systems could be used to engraft immunodeficient mice and create living disease models where you can evaluate next generation RNA therapeutics, like therapies that target mutated transcripts of FOXP3 or CRISPR-based repair of an IPEX-associated FOXP3 mutation.
Do you think the best time to intervene would be before symptoms arise?
An inborn disease like this would require genetic screening to diagnose patients before symptoms arise. What makes IPEX complicated to diagnose for clinicians is the wide variety of autoimmune symptoms that can arise. A child with IPEX can display relatively mild-moderate presentations such as eczema or diarrhea, or more severe Type 1 Diabetes symptoms and even multi-organ autoimmunity. Only when genetic screening is integrated into the healthcare system can we reliably intervene in diseases like IPEX before irreversible damage occurs.
That鈥檚 very interesting. I am glad to hear that you are enjoying working in the rare disease space. Before wrapping up, is there anything that you would like the D2R community to be aware of about yourself?
Nowadays outside the lab, I produce music and manage DJs as part of an artist collective in Toronto called The Attics. Also, I am very passionate about democratizing opportunities for students in science. In my undergrad I had the privilege of co-founding a nonprofit dedicated to supporting life science undergrads, called Nucleate Dojo. Fun fact: Nucleate Dojo is also at 涩里番! Even though I retired after my undergrad, I am very excited about the work that the current team is putting in, and I highly encourage undergrads to check them out.
