David Fung

Supervisor: Lori West

Project: Developing a cell therapy for pediatric heart transplantation from discarded tissue

Degree program:

Medicine & Dentistry-Pediatrics

Lay abstract:

For children born with a heart problem at birth (or 'congenital heart disease'), about half will need a transplant despite advances in alternative surgical procedures. A major challenge in heart transplantation is rejection of the donor heart by the recipient. This is due to specific molecules present on cells of the heart that are unique to the donor. The recipient's immune system recognizes these molecules as foreign and tries to destroy the organ. Current treatment to prevent rejection consists of medications that decrease the recipient's immune response. However, these drugs cause many side effects and make the person more prone to infections and cancer. A promising alternative strategy is to use special immune cells that naturally suppress immune responses, called 'regulatory T cells' (or 'Tregs'), as an anti-rejection cell therapy. Tregs arise in the thymus, a structure located in the upper chest in front of the heart. In children who have any heart operation, the thymus impairs access to the heart and is therefore removed and discarded. We showed previously that these discarded thymuses are a novel source of large quantities of Tregs. In our new study, we will investigate whether Tregs that specifically suppress immune responses to donor molecules can be generated by growing them with cells from the same donor as the transplant. As the Tregs develop in the thymus, they will come into contact with the foreign donor molecules. We hypothesize that this will result in development of 'donor-specific' Tregs. If these 'educated' Tregs are put into a situation where the donor transplant is being attacked by immune cells, the Tregs would theoretically suppress the attacking cells from doing damage. Taking it to the big picture, this means that Tregs that have learned to 'protect' donor organ surface molecules should be able to stop the recipient's immune system from attacking the organ. This may present us with a new therapy to tackle immune rejection in pediatric transplant recipients.

What motivated you to participate in this research?

Research for me started early when I was in high school. I had a great opportunity to be matched up with a lab here at the University of Alberta. I saw potential in pursuing research as it helped me a lot in terms of networking and opening doors towards other opportunities. I remember that first week in the lab; I was so mesmerized by everything: the equipment, the techniques, the rationale behind experiments. It was really an awesome learning experience and I knew by the end of that summer that research would be something that I would come back to summer after summer. So looking back to that first summer until now, I can identify a few reasons why I keep doing it. Firstly, I really enjoy the company of my colleagues. Being so young when I started I really appreciated the support and help that I received. My mentors and supervisors were patient with me and I truly felt that they wanted me to succeed. So I think I’m motivated by the people around me who encourage me and also set an example for me to chase after. I’m also motivated strongly by the opportunity it presents in terms of advancement. There's potential in terms of getting to know faculty, networking with like-minded people. You never know how these connections might help you in the future! The changing pace of research and the sheer depth of knowledge always keeps me motivated to continue learning. I think the more I do research, the more I realize how little I know and that pushes me to discover and learn. It has also opened my eyes to all the possibilities of research topics within a field. It's motivating to see all the potential applications in clinical practice, how it can help people down the road.

What are your career aspirations?

I’m currently a medical student. I have a strong interest in surgery and would love to specialize after graduating. Ideally, I see myself doing mostly surgery but still keeping some research interest in terms of participating in clinical research, clinical trials and collaborating in basic science research. I want to hold an academic position in surgery and be involved with teaching and research at whichever university I end up. I think it would be rewarding to be able to teach/train medical students and residents. But the most important thing for me is just to be diligent and hardworking. Career-wise it's important for me to just be the best I can be and enjoy the process.

How has this studentship helped you toward those aspirations?

I think the opportunity itself to continue the research I was doing and to further the field has been helpful. Research is such an important aspect of heading towards a surgical specialty and it helps that you show interest in research. In the near future, my studentship and research experience are ways in which I can demonstrate to the various residency programs my commitment to learning and advancing the field. There is also the opportunity to present my work and go to conferences. These are helpful to meet some of the surgeons since my work right now is in transplantation. It has also strengthened my interest in surgery and has motivated me to pursue this career path even more.