What is DERIVE's research focus?
DERIVE is where genes and the environment collide.
DERIVE's overarching research goal is to understand how variations in our genes interact with the environment to cause diseases during prenatal, postnatal and childhood development.
Did you know?
Preterm births in Canada have increased by 20% over the past two decades and are associated with increased morbidity throughout the life course and adult-onset chronic disease (1).
Congenital anomalies are the leading cause of infant mortality in Canada (2).
Asthma is the most common chronic disease in Canadian children and is more prevalent in boys than girls (3,4).
Every year, >3,000 babies are born stillborn in Canada and this number has not changed for the past decade (7).
Inflammatory bowel disease (Crohn’s disease and ulcerative colitis) in Canadian children has risen more than 50% in the last 10 years and Canada has the highest rate of child-onset inflammatory bowel disease in the world (5,6).
Most diseases of development, like the examples above, and others, are known as "complex diseases". This means that there isn't one factor that causes the disease, and research tells us that complex diseases likely involve both genetic and environmental factors. In other words, while some genes can increase the risk of developing a disease, it often takes an environmental trigger for the condition to develop. Therefore, in order to understand how these types of diseases develop, we need to study the interplay between genetics and the environment.
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THE GENETIC FACTORS
DERIVE's research will leverage big genomic datasets to identify new genetic variants that are associated with developmental diseases.
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Genetic variants are simply differences in our DNA that we inherit from our parents or that arise spontaneously in development. Each of us is estimated to have between 4 and 5 million variants in our genome!
Genetic variants are what make us unique. For example, there is a spectrum of eye colours in the human population due to variants in genes responsible for eye colour. However, some genetic variants can cause disease. One example of this is a variant in a gene called CFTR, which causes cystic fibrosis, a disorder that damages the lungs, digestive tract, and other organs.
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But did you know that most variants are actually 'inactive' and don't appear to have a positive or negative impact on our health? These variants are the focus of DERIVE's research. We hypothesise that these variants influence our biological response to certain environmental exposures and that it is this gene variant-environment interaction that triggers the pathogenesis of developmental diseases.
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A key question DERIVE will answer is why do some people exposed to an environmental exposure develop disease and others do not? Think about smoking, not everyone who smokes will get lung cancer. Why is that? Recent research shows it has to do with what type of genetic variants people express (8).
THE ENVIRONMENTAL FACTORS
DERIVE's research will explore how common environmental exposures found in air, water, food or soil in Canada can interact with our genes to cause developmental diseases.
The environmental exposures we are focused on can generally be grouped into three categories:
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1) Heavy Metals:
Heavy metals are a group of naturally occurring elements that have a high atomic weight and density. Some common heavy metals include arsenic, lead, mercury, cadmium, and chromium. They are found naturally in the earth's crust, but human activities such as mining, industrial processes, and agriculture have increased their levels in the environment.
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2) Air Pollution:
Air pollution is contamination of the indoor or outdoor environment by any chemical, physical or biological agent that modifies the natural characteristics of the atmosphere. Examples of air pollutants include particulate matter, ozone, nitrogen dioxide, carbon monoxide and sulphur dioxide.
3) Climate Change:
Climate change refers to the long-term changes in the Earth's climate patterns, including changes in temperature, precipitation, and sea level rise, that are caused by human activities, particularly the emission of greenhouse gases, such as carbon dioxide and methane, into the atmosphere.
Which diseases will DERIVE study?
Adverse Pregnancy Outcomes
Childhood Disease
Developmental Origins of Adult-Onset Disease
DERIVE is at the forefront of cutting-edge research on the complex interplay between genes, environment, and development. DERIVE's research program has three overarching research themes: 1) Adverse Pregnancy Outcomes, including preterm birth, stillbirth and congenital birth defects, 2) Childhood Disease, including inflammatory bowel disease, kidney disorders and asthma, and 3) Developmental Origins of Adult-onset Disease.
Our team is currently undertaking several exciting projects that have the potential to transform our understanding of these critical areas of study. However, we're always looking for new and innovative ways to push the boundaries of what's possible. We invite you to reach out to us at derive@muhc.mcgill.ca if you're interested in collaborating with us!
Examples of Current Projects
Developing human organoids to model development
Organoids are three-dimensional miniature structures that serve as excellent in vitro models of human organs. DERIVE is setting-up human organoids in the lab using induced pluripotent stem cells. This innovative model system will allow us to test the impact of multiple genetic variants and environmental exposures on the development of various organs, such as the intestines, kidneys, and lungs.
Effect of in utero heavy metal exposure on fetal organ development
Arsenic is a widespread environmental contaminant and one of the World Health Organization's top 10 chemicals of major public health concern. Although Canada has established regulations to limit the amount of arsenic in water, food and air, millions of individuals are estimated to live in areas that exceed these standards. This project aims to understand the impact of arsenic toxicity on embryogenesis and pregnancy outcomes using mouse models. In addition to arsenic, we will also study other heavy metals such as lead and cadmium. This project is undertaken in partnership with Dr. Koren Mann, McGill University.
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The link between air pollution exposure and developmental outcomes and disease
Airborne pollutants are a major environmental health hazard that poses a significant threat to human health worldwide. Pregnant people and children are particularly vulnerable to the adverse effects of air pollution exposure. Using local air pollution exposure data, this epidemiological study aims to understand the impact of ultrafine particles on the developmental origins of disease, including birth outcomes and asthma. This project is undertaken in partnership with Dr. Scott Weichenthal, McGill University and Dr. Eric Lavigne, Health Canada.
Identifying genetic variants associated with developmental diseases in the UK Biobank
The UK Biobank is a large-scale genetic and health database that includes information from over 500,000 participants in the United Kingdom. We will leverage our access to this large cohort and perform genome-wide association studies to identify novel variants associated with developmental diseases. Following these analyses, we will confirm our findings in Canadian cohorts. This project is undertaken in partnership with Dr. Jamie Engert, McGill University.
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References
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Institute for Human Development, Child and Youth Health – Canadian Institutes of Health Research. https://cihr-irsc.gc.ca/e/49819.html (Accessed March 15th, 2023).
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Statistics Canada. Table 13-10-0395-01 Leading causes of death, infants. DOI: https://doi.org/10.25318/1310039501-eng (Accessed March 15th, 2023).
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Asthma Canada. https://asthma.ca/wp-content/uploads/2021/06/Asthma-Canada-2020-Annual-Report.pdf (Accessed March 15th, 2023)
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Canadian Public Health Infobase. https://health-infobase.canada.ca/datalab/asthma-blog.html (Accessed March 15th, 2023)
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Crohn’s and Colitis Canada. https://crohnsandcolitis.ca/About-Us/Resources-Publications/Impact-of-IBD-Report (Accessed March 15th, 2023)
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The Canadian Children Inflammatory Bowel Disease Network. https://cidscann.ca/ (Accessed March 15th, 2023)
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Statistics Canada. Table 13-10-0428-01 Live births and fetal deaths (stillbirths), by type of birth (single or multiple). DOI: https://doi.org/10.25318/1310042801-eng (Accessed March 15th, 2023).
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Huang et al. (2020). Single-cell analysis of somatic mutations in human bronchial epithelial cells in relation to aging and smoking. Nature Genetics. 54, pages 492–498. https://www.nature.com/articles/s41588-022-01035-w