Supporting promising young scientists in gene and stem cell research

OCTOBER 14, 2022

As part of our commitment to attracting new talent to the field of cystic fibrosis research, Cystic Fibrosis Canada is supporting two bright, early-career researchers with a travel award to enable them to attend Canada’s premier stem cell and regenerative medicine conference, the Till and McCulloch meetings.

Stem cells hold incredible promise in the field of cystic fibrosis, including the possibility of someday finding a cure – that’s why supporting gene and stem cell research is one of our highest community health priorities.

Enrolled at the University of Toronto and working in a lab at SickKids, PhD candidate Henry Quach is trying to understand how cystic fibrosis lung disease develops in the early stages of fetal development, when the lungs are taking shape.

In two stages of fetal lung development, expression of the CFTR protein is highly up-regulated. At this time, the fetus’s lungs are taking shape and the cells are differentiating into different types.

Using stem cells derived from the exciting CFIT Program at SickKids and a stem cell model of the lung developed in the lab of his PhD supervisor Dr. Amy Wong, Quach is investigating the impact of the CFTR protein during these critical stages of lung development.

He is testing the hypothesis that the CFTR protein is important in regulating developmental pathways in the lungs in a way that could pre-dispose a person with dysfunctional CFTR protein such as those who live with cystic fibrosis to worsening lung function. This could explain structural abnormalities such as increased airway thickness and narrower airways that have been observed in newborns with cystic fibrosis even when they show no respiratory symptoms.

“For example, if the ratio of different cell types is skewed, that could have an impact on how the lung functions postnatally,” explains Quach. “It’s very important to understand how the CFTR protein impacts lung development. This might help us understand if there’s anything we can do in terms of earlier treatment strategies for people with cystic fibrosis.” 

Meanwhile, at the University of Guelph, microbiology PhD student Brenna Stevens is using thin, precision-cut slices of animal lung to test possible viral vectors that might one day deliver gene therapy to provide a correct copy of the CFTR gene to people with cystic fibrosis. She gets the lung samples from the teaching abattoir on campus, where they would otherwise go to waste. The lung slices serve as a more accurate model for live lungs than cultured cells, explains Stevens.

“A Petrie dish is very one-dimensional, but in a real lung, countless cells interact in many different ways. The slices contain the lung’s natural architecture and population of many different types of cells,” explains Stevens. “They work as a great model and are so much faster and cheaper than working with live animals.”

Once a successful vector is found, it would be tested in animals – but this is expensive and time-consuming work. By screening candidates in slices of animal lungs, Stevens’s work can accelerate the selection process and ensure that only the best candidates make it to the animal testing stage.

There are hundreds of potential candidates for delivery vectors, but not just any virus will do. It has to be harmless to humans, of course, but it also has to be able to carry the large CFTR gene, or two portions that can recombine once in the cell.

The end game – still a long way off – is to develop gene therapy for cystic fibrosis. Using this method, a person’s cells would produce the correct CFTR protein from the DNA delivered to the cell, while leaving their own DNA (including their CF mutations) untouched.

“Gene therapy is a way to supply a person with cystic fibrosis with a correct copy of the CFTR gene. One day, we hope to be able to insert the vector into the person’s cells, where it would deliver a correct copy of the CFTR gene so that the cells could start producing the correct CFTR protein. In theory, you could do this at any time in a person’s life,” explains Stevens. “The person keeps their original genome, but we’re also supplying them with a correct copy of the CFTR gene.”

By creating a better, faster way to screen candidates for the viral vector, Stevens’s work could hasten this type of research along.

Cystic Fibrosis Canada is pleased to be able to support these two young scientists as they attend a conference where they are sure to meet colleagues and potential new collaborators. Both Stevens and Quach will present posters on their innovative work at the event.

The Till & McCulloch Meetings take place October 3-5, 2022 in Vancouver. For more information, visit stemcellnetwork.ca.