Science & Research

Full circle

At the age of 12, Meghan Azad participated in a clinical trial for a new asthma medication. Today, 20 years later, she is a key member of a team at the Children's Hospital Research Institute of Manitoba that is working to unravel the underlying causes of the disease that once hampered her ability to breathe

Researcher Meghan Azad.
Researcher Meghan Azad.
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Foundation raises money to advance care

Researchers at work

BY HOLLI MONCRIEFF
Winnipeg Health Region
Wave, January / February 2015

Meghan Azad started to become curious about asthma at an early age.

In 1994, at the age of 12, she was diagnosed with the disease and was enrolled in a study headed by a number of local researchers, incuding Drs. Allan Becker and Estelle Simons.

At the time, they were recruiting for a clinical trial on a new drug treatment for children with the breathing disorder. The experience inspired Azad.

"From there on, I decided I was interested in health research that would make a difference," she says. "I wanted to participate in medical science that would help people like me."

Today, 20 years later, Azad has achieved her dream. She is an epidemiologist at the Children's Hospital Research Institute of Manitoba, and is considered one of the top young researchers in her field. Becker and Simons, meanwhile, are now her colleagues.

"The experience has come full circle," she says.

As one might expect, Azad's early interest in asthma continues through her research into the developmental origins of health and disease. This is a relatively new field of investigation that focuses on the role the earlylife environment plays in the onset of diseases and conditions, such as asthma, Type 2 diabetes and obesity.

And, as it turns out, the research institute is the perfect setting to carry out such work.

Located on the fifth floor of the John Buhler Research Centre at the Bannatyne Campus of the University of Manitoba's Faculty of Health Sciences, the research institute, formerly known as the Manitoba Institute of Child Health (MICH), is home to 270 pediatric medical researchers, technical staff, students and support staff.

Over the years, the research institute, which opened in 2001 with 50 researchers and staff, has developed a reputation as one of the finest child health research centres in Canada, particularly in the major research themes of biology of breathing and diabetes.

And that reputation is expected to grow in the coming years as the research institute continues to build on the work of Azad and other researchers under the leadership of CEO and Scientific Director Dr. Terry Klassen.

For example, the research institute is in the process of forming a new research cluster - the Manitoba Developmental Origins of Chronic Disease in Children Network (DEVOTION) - that will establish this province as a leader in Azad's field of developmental origins of health and disease.

Led by Dr. Jon McGavock, this initiative will bring together clinical and basic researchers from multiple disciplines to create a team that will work together to unravel the early-life origins of health and disease, and design new approaches for prevention.

Klassen says the new cluster is important because it will focus on the root causes of childhood diseases, particularly breathing disorders and Type 2 diabetes, two of the most common health issues children face.

"I really want to address the key issues that are affecting children and youth and their families," says Klassen. "It's an investment in the future. If you can give kids a better start, they'll have a higher quality of life," he says. "We want the very best, cutting-edge information for our children."

As Klassen explains, the main benefit of having the research institute attached to the Children's Hospital is that it encourages researchers and clinicians to collaborate on various research projects that will enhance care and improve patient outcomes.

"Because of the close connection, our ability to bring innovation to the bedside is very efficient," says Klassen. "As we get new knowledge, we bring that information back to the Children's Hospital. We have the ability to take challenges into the scientific environment that much faster. The time it takes for research questions to be addressed is much shorter," he says.

This type of environment helps attract the best and brightest in the field, says Klassen. "The best children's hospitals around the world have had a commitment to innovation and discovery," he says. "Meghan's a great example. She could have gone anywhere, but because we have this institute right here, we could entice her to stay."

Azad, meanwhile, says she feels lucky to be able to work in an organization focused on child health. "This is the perfect place to do this kind of research," she says.

She is particularly enthusiastic about her latest research study, which involves investigating whether the bacteria found in the intestines of newborns plays a role in the development of various conditions and diseases, including allergies, Type 2 diabetes, obesity, and, of course, asthma.

As she explains, these bacteria - collectively called the microbiome - are established during infancy and play a critical role in immune-system development and host metabolism.

"The microbiome refers to the trillions of 'friendly' bacteria that live on us and in us, and the majority reside in our gut," says Azad. "They're a big part of our being, and we want to know what role they play in developing a healthy immune system in early life. We're starting to link changes in the infant gut microbiome to health and disease later in childhood."

Scientists have known about the importance of the gut microbiome for some time, but samples couldn't be studied effectively until about 10 years ago, Azad explains. "The only way to study them was to grow them in a culture dish in the lab, which is difficult since many gut bacteria do not survive outside of the human body. With new DNA sequencing technology, we can study the gut microbiome without relying on laboratory cultures," she says.

Azad and her colleagues from the Synergy in Microbiota (SyMBIOTA) research team - including lead researchers Anita Kozyrskyj, from the University of Alberta, and James Scott, from the University of Toronto - have already won an award for their research in this area. Earlier this month, the Canadian Medical Association Journal presented them with the Bruce Squires Award for a study entitled Gut Microbiota of Healthy Canadian Infants: Profiles by Mode of Delivery and Infant Diet at Four Months. The study demonstrated that an infant's gut flora could be influenced by how the infant was delivered or whether he or she was breastfed, and is expected to have an impact on clinical practice.

In her current study, Azad is investigating bacteria in breast milk, which she suspects are an important source of gut bacteria for newborns. The research draws on data collected under the umbrella of the Canadian Healthy Infant Longitudinal Development Study (CHILD), which tracks the lives of 3,500 children in Canada who were born between 2010 and 2012. The initiative involves 44 researchers working out of seven universities and 11 hospitals in Manitoba, British Columbia, Alberta, and Ontario.

While Azad is the one "crunching the numbers" on this project, she says many others are involved in the work. "I've been the one to link the microbiome findings with the information in the CHILD study and analyze those results, but all of this research involves huge teams of people," she says.

In order to study the gut microbiome, for example, fecal samples have to be taken from the children who are participating in the study. Investigators in Toronto receive the fecal samples and sequence the microbiome DNA. The results are sent back to the research institute for analysis and comparison to other data in the study. The object of the exercise is to determine whether children who develop certain illnesses or conditions also have a different microbiome.

"When children get asthma and allergies, we want to know what was different about them in early life that may have predisposed them to these conditions. It's a complicated question that is going to have a complicated answer."

Although the study is still under way, Azad says the early findings indicate that our super-clean, sterilized environment may be contributing to health problems of children.

"Antibiotics are often used unnecessarily. There's this idea now that we're too clean. We're sterilizing everything, and because of this, our infants' immune systems don't learn to tell the difference between the friendly microbes and the harmful ones," says Azad. "Being exposed to a little bit of dirt and germs is good for us, especially in early life."

The theory is in line with findings from an earlier study at the research institute involving children born in 1995. The Study of Asthma, Genes and Environment (SAGE) found that those who receive antibiotics in the first year of life had a greater risk of asthma and obesity as teenagers, she says.

"We're really interested in the obesity angle. Childhood obesity has skyrocketed. Some cases may be due to changes in our lifestyle, but our microbiome has likely changed in the last 10 to 30 years as well. We answer some questions, but we also generate more as we go."

The findings from these studies are already changing the medical care children receive and the advice given to parents and expectant mothers. "In the 1995 SAGE study, two-thirds of the children received antibiotics in their first year of life. Fifteen years later in the CHILD study, this number has gone down to one-third," says Azad.

"I see this as a good sign that the message is getting out. As we learn more about what aspects of our environment are contributing to childhood disease, we'll be able to start making recommendations to parents. We'll be able to design new interventions, therapies and prevention strategies."

Azad's study is, of course, just one of many underway at the research institute.

There are currently 43 studies being conducted by researchers, including clinical trials of new treatments for rare and ultra-rare hereditary metabolic disorders, an evaluation of a peer-mentoring program for obesity prevention in First Nations communities, a unique study of children born to mothers with diabetes, and research on a possible link between vitamin D deficiency and dental cavities.

As Klassen explains, all of these research projects are designed to help kids lead longer, healthier lives by tackling issues that are known to affect large numbers of Manitoba children.

"Our research is very much community based," Klassen says. "We need to ensure all children in Manitoba receive the highest level of care."

Holli Moncrieff is a Winnipeg writer.

Wave: January / February 2015

About Wave

Wave is published six times a year by the Winnipeg Health Region in cooperation with the Winnipeg Free Press. It is available at newsstands, hospitals and clinics throughout Winnipeg, as well as McNally Robinson Books.

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