Taking Aim at Cystic Fibrosis
In Canada, cystic fibrosis (CF) is the most common fatal genetic disease affecting children and young adults. An estimated 1 in every 3,600 children born in Canada are affected by CF.
Cystic fibrosis affects multiple systems throughout the body, though symptoms manifest primarily within the digestive and respiratory systems. Mutations of the CFTR gene affect fluid transport in the lungs, resulting in complications that include increased mucus viscosity, susceptibility to pathogens, and changes to lung immunity. As a result, individuals with CF experience respiratory symptoms that include persistent cough, wheezing, shortness of breath, and frequent chest infections including pneumonia.
Though research has helped many individuals with CF live longer by managing their symptoms more effectively, there remains no cure and the efficacy of available treatments varies greatly between individuals. In addition, parents who care for children affected by CF may suffer from symptoms of depression and anxiety, as caregivers can sometimes lose focus on their own mental health needs.
Jenny Nguyen is pursuing a PhD under the supervision of Dr. Jeremy Hirota
Jenny Nguyen is a graduate student at McMaster University, studying cell biology and the molecular mechanisms of cystic fibrosis. She is working towards a doctorate under the supervision of Dr. Jeremy Hirota, who holds the Canada Research Chair in Respiratory Mucosal Immunology, and is co-founder and CEO of Infinotype, a start-up biotechnology company focused on lung diagnostics. Dr Hirota is also Chair of the College of Health Inventors at McMaster University, which advocates for bringing university research to the marketplace for maximal social and economic benefits.
The Hirota laboratory at St. Joseph’s Healthcare Hamilton is uniquely poised to facilitate Nguyen’s research. With access to quantitative PCR and western blot equipment, as well as the ability to culture primary cells, Dr. Hirota’s graduate students have the tools they need to pursue their novel research projects. In addition, the lab’s ongoing collaboration with The Hospital for Sick Children (SickKids) offers Nguyen access to donors, providing the lab with human airway epithelial cells from both healthy individuals and patients with CF, which is critical to her work.
“With the specialized equipment necessary to grow and culture primary cells from healthy and CF donors, Dr. Hirota’s Lab provides me with all the necessary resources. It's also the perfect environment for me to pursue my research and learn how to bring it to market. This research will not only improve the current limited therapeutics for CF but could have potential applications for other lung diseases that are affected by acquired CFTR dysfunction.”
The development of single drug therapeutics that directly target CFTR function has led to the ability to treat a larger CF patient population. However, with over 2000 known mutations to the CFTR gene, some patients remain unresponsive to this type of therapy. This led Nguyen to look for alternative drug pathways. Instead of targeting CFTR directly, she is working on an alternative strategy that targets an intracellular messenger molecule called cAMP as well as other proteins.
Nguyen’s hypothesis is based on prior work with these proteins from the Hirota lab. She will use highly specialized equipment to grow cell cultures from a variety of CF donor cells. From there, she will identify samples with high expression levels of three specific proteins and genes involved in CFTR activity. The samples will be tested with a combination of protein inhibitors to observe any effects on CFTR activity, and to determine the optimal dosage of these inhibitors.
Jenny Nguyen in the Hirota Lab at St. Joe’s
Nguyen also sees potential for her research to be applied beyond cystic fibrosis. For instance, her work may benefit non-CF patients with COPD who have acquired CFTR dysfunction through smoking.
“It’s crucial that we cultivate our young scientists with the skills they need to conduct groundbreaking independent research, while also encouraging their creativity,” says Dr. Hirota. “We don’t want our students to be pigeonholed to one specific problem, when their work may have broader impacts in other areas as well. Encouraging imaginative thinking is a priority.”
The work of Jenny Nguyen and the Hirota lab is just one example of many that demonstrate how St. Joe’s researchers are educating the world’s best.