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Dr. Nasrin Mesaeli
Principal Investigator, Vascular Molecular Biology
Institute of Cardiovascular Sciences
In Detail
SEARCHING FOR THE SWITCH THAT ACTIVATES STROKE
Dr. Nasrin Mesaeli’s laboratory is studying changes that occur at the molecular level in the walls of blood vessels that in turn lead to the development of cardiovascular diseases. “The nucleus of the cell contains all the genetic information. One can think about the nucleus as a switchboard that is very tightly regulated. Different factors from outside of the cell can regulate the genes by turning them on or off”, Dr. Mesaeli explains. “If a gene is turned on or turned off prematurely (or late) then the system will become defective. In cardiovascular disease and stroke, factors like smoking or diet can make the situation worse. Our research is focussing on finding the genetic factors which cause vascular disease.” By using various techniques for the analysis of patterns of gene expression that occur when a stroke is developing, Dr. Mesaeli will identify specific genes or gene products that appear to be linked to the disease process. These genes will be targeted for further studies to determine the mechanisms at work.
DETERMINING WHAT IS TURNED ON AND WHAT IS TURNED OFF IN BLOOD VESSELS
In studying stroke, major efforts have been directed toward understanding the effect of the disease on the brain tissue itself. Less attention has been paid to changes in the blood vessels – either those that rupture in the brain to cause a hemorrhagic stroke or those that close off nourishment to the brain to precipitate an ischemic stroke.
Dr. Mesaeli’s lab will use molecular biology techniques to study the genes and gene products which are linked to the development of stroke and other cardiovascular diseases. Using DNA microarray technology, thousands of genes from the blood vessels of rats with a genetic predisposition to stroke are being studied to determine the levels of expression at various stages of disease. To date, a number of genes have been identified that warrant further study.
Another technique being used in Dr. Mesaeli’s investigations involves subtraction libraries. This involves comparing diseased tissues with healthy tissues to determine which genes are turned on or turned off in the disease. Rat models of stroke are being used for these studies.
Dr. Mesaeli is also collaborating with surgeons at St. Boniface General Hospital in studying atherosclerotic human tissue which is removed from patients at risk of ischemic stroke. DNA microarray analysis of this tissue has the potential to narrow the range of potentially promising genes for study and achieve clinically relevant results more quickly than doing animal studies alone.
MAKING A MOUSE
Dr. Mesaeli’s expertise includes the development of transgenic and knock-out mice, so the next phase of her research will involve creating a mouse model to investigate the direct relationship of specific genes to disease development. A transgenic mouse is one in which DNA is injected into a fertilized egg and can be used to over-express a gene in the mouse. A knock-out mouse is created when cells that do not produce the protein being studied are transplanted into an embryo to generate a mouse which does not have this protein. Today’s technology enables researchers to create animal models in which the gene being studied is present or absent in just one type of tissue or cell.
The goal in developing an animal model is not only to study how the disease develops, but also how it can be prevented. It can become a powerful tool for monitoring the development disease over time and under different conditions, for testing different drugs or gene therapies, and for developing methods of screening.
For more information, please contact:
Dr. Nasrin Mesaeli
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