William Foulkes, MBBS, PhD, is a James McGill Professor in the Departments of Medicine, Oncology and Human Genetics at McGill University and a researcher-clinician who has practiced clinical genetics at McGill-affiliated hospitals since 1996.
Dr. Foulkes and his research team work with individuals and families who may have inherited susceptibility to develop tumours. “We first saw a connection between our research and RNA when we were working with a family experiencing thyroid goiter,” says Dr. Foulkes, a member of the recently created McGill Centre for RNA Sciences, who also heads cancer genetics research labs at the Lady Davis Institute for Medical Research of the Jewish General Hospital and the Research Institute of the McGill University Health Centre.
“Although goiter is not unusual, it does not normally run in families. It turned out this condition can be caused by mutations in the DICER1 gene, which is a critical component of microRNA production,” explains Dr. Foulkes. “These mutations can result in DICER1 syndrome, which tends to cause benign tumours. However, people with the syndrome, especially children and adolescents, are also at risk for cancers. So, my interest in RNA stems from those two threads: trying to find out more about the phenotypes (observable characteristics) associated with these mutations and trying to understand what goes wrong with DICER1 such that it leads to problems for people and families.”
With this in mind, we spoke to Dr. Foulkes about his hopes for what RNA research more generally, and the new multidisciplinary Centre more specifically, could contribute to improving clinical care.
RNA research had a tremendous impact on the COVID-19 pandemic. How important will it be in DICER1 research?
As researchers, our big question is why children with DICER1 syndrome develop very rare tumours. It doesn’t appear to cause common cancers like breast cancer, so there must be something very specific involved. Our research team looked at this area and found that in pituitary blastoma, a very rare childhood tumour of the pituitary gland, one type of RNA encoded by the PRAME gene was overexpressed 500 times compared to expected levels, and indeed, PRAME protein was also overexpressed – not just in pituitary blastoma, but in other tumours.
For you, what makes the McGill Centre for RNA Sciences so important to the future of medicine and research?
I think the COVID-19 pandemic brought everyone’s attention to RNA. The difference that mRNA vaccines made to our lives is remarkable. However, it is important to note that a lot of important RNA research has been done at McGill by people like Thomas Duchaine, Marc Fabian, Jerry Pelletier, and of course, Nahum Sonenberg. But, through being involved in DNA to RNA: An Inclusive Approach to Genomic-based RNA Therapeutics (D2R), I learned there are a lot of RNA researchers that I don’t know. The Centre will bring all these people together and fully integrate their multiple interests and areas of expertise. We have outstanding researchers at McGill who have already made their name in RNA research, which is a clear reason why this is an ideal location.
What do you hope to bring to the Centre?
I think I bring a connection to the clinical world. For example, we recently came across a particular variant in a family, but we didn’t know how the variant resulted in any phenotype. So, we worked with Marc Fabian and, together, we have shown how this variant leads to DICER1 syndrome. So, I think my main contribution will be to connect RNA researchers with people in the clinical world and in the DICER1 community.
What are you hoping the Centre will contribute to RNA research and clinical care?
Novel therapies and cancer vaccines would be fantastic, as well as therapies that emerge from the microRNA biogenesis work that we and others have done. For me, developing therapies based on microRNAs and specific RNA targets would be very exciting.