From Child to Adult: The Montreal Children’s Hospital Research Institute

Source: McGill University’s Faculty of Medicine In Focus alumni magazine - Spring 2008

Par : Patrick McDonagh

As a young resident in obstetrics and gynecology, Jacquetta Trasler, MDCM’80,PhD’87, was struck by the number of birth defects she witnessed – usually from unknown causes.

Some fathers had undergone chemotherapy and radiation treatment for testicular cancer, and I wanted to know if these treatments could affect sperm and, potentially, the children of the treated men,” says Trasler, whose curiosity brought her back to McGill to earn her PhD. No researcher had ever studied this question at a basic level, so her research involved collecting animal – rather than human – evidence. Today, this animal research has provided enough information to allow clinical studies of men who have undergone these treatments, and Trasler, now the scientific director of the Montreal Children’s Hospital (MCH) Research Institute, is confronting new research questions. “About one per cent of Canadian children are conceived using assisted reproductive technology,” she says, “so we need to ensure the safety of the process, which can affect gene expression profiles later.”

Her research focuses on the earliest stage of development, as gametes develop into early embryos – and is also one of the initial stages of research on the human life cycle performed at the MCH. “But all our work here is interrelated,” she says. “If my group sees something unusual happening early in the cell culture, then we can look for consequences of that at a later stage. If there is an effect on kidneys, for example, we can track the molecular pathways, the genes, and the environmental interactions that may have led to this effect.” The MCH has a highly regarded nephrology research group that could then examine the interaction between the relevant genes and the kidneys.

“Our researchers are primarily involved in developmental events related to childhood, running from the prenatal period through infancy, childhood and adolescence, including the childhood origins of adult disease,” explains Harvey Guyda, physician-in-chief at the MCH and chair of Pediatrics in the Faculty of Medicine. “And this happens from laboratory science – especially involving genetics – to clinical research. It’s all connected. Even when we talk about cancer, we’re talking about genetics as well.”

Guyda points to Michael Kramer’s groundbreaking studies in preterm births and mortality; to Robert Koenekoop, MDCM’89, and his recent discoveries in the genetics of childhood blindness; to Rima Rozen, BSc’75, PhD’81, and her research linking colorectal cancer and diets low in folates; and to Francine Ducharme, MSc’90, and her renowned work on asthma treatment. “Some of this research is basic and some is clinical, but the combination brings us all the way from the gene to the patient, and enables us to follow patients from the earliest stages through adolescence,” says Guyda.
The MCH Research Institute includes about 50 funded investigators, 80 graduate students and 25 post-doctoral fellows, all working in a dynamic environment with an open lab design.

“Clinician-scientists are working alongside basic developmental biologists, and there is a lot of crosstalk,” says Trasler. “And when we move to the MUHC’s new facilities at the Glen site in Montreal’s West End, we’ll have children and adult patients at one site. It will give us an amazing opportunity to follow people along their entire life trajectory.”

Recent evidence suggests that assisted reproduction increases the risk of babies being born with gene expression abnormalities known as imprinting disorders. Amanda Fortier, a doctoral candidate working with Jacquetta Trasler, has found that mice that receive ovulation-inducing hormones have more of these abnormalities.

“But the abnormalities appear more often in the placenta than in the embryo,” she explains. “This means that the placenta, which is normally discarded after birth, might provide a good non-invasive screening tool to determine if further tests on the baby are required.”

The finding has sparked a partnership with other researchers at McGill, as well as in Ottawa and Toronto, to collect and test placenta samples from human infants. “My lab work has translated very directly to clinical research,” says Fortier. “Hopefully we will turn up something really interesting.”