Dr. Mathieu Lemaire The Hospital for Sick Children, Research Institute, Ontario
KRESCENT NEW INVESTIGATOR AWARD 2017-2010 KRESCENT INFRASTRUCTURE AWARD 2017-2018
Dr. Mathieu Lemaire finished his medical training at McGill University in 2004 and then moved to Toronto to learn Paediatrics and Nephrology at The Hospital for Sick Children. Then, he went to Yale University (New Haven, CT) to pursue a PhD in Investigative Medicine under the supervision of Dr Richard P. Lifton as a KRESCENT post-doctoral fellow.
Blood vessels are like roads that can reach any cell of our body. We call the cells that line blood vessels "endothelial cells". Blood flows fast in normal blood vessels, but it is slow when there is damage. It forms a blood clot. This is similar to a “good traffic jam”: it helps repair injured blood vessels. The body must control the machines that help with repair to avoid “bad traffic jams”. Healthy blood vessels don't need blood clots.
In the lab, we study the function of endothelial cells in the kidneys. We work on a disease called "atypical hemolytic-uremic syndrome". For simplicity, we call it "aHUS". Patients with aHUS get kidney failure. Why? Blood clots form in the blood vessels of the kidneys. These clots prevent normal blood flow in kidneys. Blood flow is important to deliver food and oxygen to the kidneys.
We found that mutations in the gene diacylglycerol kinase epsilon (DGKE) can cause aHUS. Each cell in the body contains DNA, a code made of genes. Genes make proteins—the building blocks of cells. Mutations are changes in the DNA that cause abnormal function of a protein. For our patients, the mutations prevent DGKE from working well.
This project will tackle four different tasks to help us understand better DGKE function in endothelial cells:
- Figure out how a deficiency in DGKE leads to abnormal AKT function in endothelial cellsFind out how
- abnormal eNOS function affects the function of blood vessels that have no DGKE protei
- nDetermine how DGKE deficiency prevents endothelial cell to withstand normal blood flowStudy how DGKE
- mutations found in patients with aHUS affect the function and structure of DGKE enzymes
This research is important so we can start thinking about new treatment for this disease. Studies on the function and structure of DGKE could be helpful to diagnose patients with new mutations. It will also teach us a lot about how normal blood vessels prevent blood clot formation.
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