Basic Science Lead: Vern Dolinsky
Basic Science Researchers: Abdel Soussi Gounni, Adrian West, Ann Yi, Charles Wong, Christine Doucette, Garry Shen, Grant Hatch, James Davie, Joe Gordon, Jon McGavock, Kangmin Duan, Paul Fernyhough, Prashen Chelikani, Richard Keijzer, Saeid Ghavami, Shyamala Dakshinamurti, Tiina Kauppinen, Todd Duhamel
The Basic Science Pillar utilizes cell-based and rodent models to identify novel biomarkers and pathways of chronic disease development.
We also integrate information from clinical and population health pillars to evaluate causation and validate markers of clinically relevant markers of chronic disease risk.
We use state of the art imaging, physiological testing, molecular biology and metabolic core facilities in the Children’s Hospital Research Institute of Manitoba to dissect the mechanisms through which early life exposures affect a child’s risk for chronic disease.
Congenital Diaphragmatic Hernia
How can microRNAs - small pieces of genetic code that function as gene regulators - disrupt abnormal lung development in babies born with a hole in the diaphragm?
Every day, 150 babies are born with a hole in the diaphragm and abnormal lung development, a disease known as congenital diaphragmatic hernia (CDH). We currently do not know why their lungs develop abnormally. It is important to investigate this, since 1/3 of these babies die from respiratory problems after birth. In our laboratory, we have identified a small piece of genetic code - a microRNA called miR-200b - that might play a very important role during the abnormal lung development in CDH babies.
We will investigate how miR-200b regulates lung development and how disrupted miR-200b abundance leads to abnormal lung development in CDH. Our studies will help to better understand lung development in CDH and we will use this information to plan future therapies aimed at improving lung development in these babies before they are even born.
Investigating the developmental origins of childhood obesity - Environment, Genes & Chronic Disease (EGCD)
Obesity is the fastest growing chronic illness in Canada, not only among adult men and women, but also in pregnant women and children. Pre-pregnancy obesity is a factor that increases the likelihood that a woman will develop diabetes during pregnancy. In turn, exposure to diabetes during pregnancy influences the risk for obesity development in children, according to recent findings.
Our understanding of how a mother’s diabetes during pregnancy influences the development of obesity in children is incomplete. We plan to study populations of children and their mothers in combination with rodent models of diabetes during pregnancy, to determine how the maternal environment influences the development of obesity in their children. Our research aims to identify new biomarkers of obesity risk that could be used to prevent the extensive health and financial burden of obesity in children and future generations.
The Impact of Human-derived Human Milk Fortifiers (H2MF) on Gut Microbiota Development and Oxidative Stress in Premature Infants
Breastmilk provides the best nutrition for healthy infants, but breastmilk alone cannot meet the unique nutritional needs of very small premature newborns. These infants require milk supplemented with fortifiers (HMF), which have traditionally been made from cow milk. However, cow milk alters the gut microbiota and causes oxidative stress in young infants. New fortifiers made from human milk (H2MF) have recently become available, but are not widely used in Canada. Ours will be the first study to study the effect of new H2MF on gut microbiota and oxidative stress in premature infants.
This research will help inform feeding recommendations for premature infants and guide the development of improved milk fortifiers in the future.
June 2016 Catalyst Grants
Natural health product intervention during diabetes in pregnancy – Grant Hatch, Vern Dolinsky, Christine Doucette
This study will test the hypothesis that supplementation of gestational diabetes-inducing high fat and sucrose diets with resveratrol or berberine during pregnancy prevent adverse health outcomes in the offspring (e.g. neurocognitive deficits, cardiovascular, chronic lung and metabolic diseases) via improved mitochondrial function and reduced oxidative stress/inflammation.
5 hydroxymethylcytosine in nuclear and mitochondrial DNA – Jim Davie, Vern Dolinsky, Joe Gordon, Brandy Wicklow
This study will test the hypothesis that incorporating the epigenetic signature of 5 hydroxymethylcytosine of nuclear and mitochondrial DNA from white blood cells with that of nuclear 5 methylcytosine will produce a superior biomarker. The aim is to determine which of the multitude of methods to determine the nuclear and mitochondrial genomic 5 hydroxymethylcytosine is most efficient, reliable and cost effective.
Assessing asthma risk with gestational diabetes in murine models – Andrew Halayko, Vern Dolinsky, Christopher Pascoe
The first aim of this study is to develop the first mouse model of house dust mite sensitivity for use in determining asthma risk following environmental exposures. The second aim is to determine whether maternal diabetes during pregnancy affects the risk for house dust mite -challenged induced airway hyper-responsiveness and inflammation in offspring.
To evaluate the effects of antenatal and post-natal statin therapy in an animal model for abnormal lung development and congenital diaphragmatic hernia – Richard Keijzer, Aruni Jha, Nagmeh Khoshgoo
The objective of this study is to evaluate the effects of antenatal and postnatal statin therapy in an animal model for abnormal lung developmental and congenital diaphragmatic hernia.
Epigenetic mechanisms and associations with septo-optic dysplasia: a pilot project – Celia Rodd, Brandy Wicklow, Asis Mhonni, Pinzhoo Hu
This study is a pilot project to assess methylation of cytosine in CpG dinucleotide patterns in genome-wide methylation analysis in children with septo-optic dysplasia. It tests the hypothesis that children with optic nerve hypoplasia/septo-optic dysplasia spectrum will have differentially methylated CpGs and differentially methylated regions between this disease and controls.