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CHS Research Grants for 2010

An evaluation of FVIII expression in phenotypically distinct endothelial cells.


Dr. Christine Hough
Dept. of Pathology and Molecular Medicine
Queen's University
First year funding

Co-Investigator: Dr. David Lillicrap

Factor VIII (FVIII) is synthesized in some but not all endothelial cells. Our understanding of mechanisms that regulate this FVIII expression is very poor, in large part because expression of FVIII is rapidly lost when these cells are isolated and cultured. However, culture conditions do not reflect the natural endothelial environment in blood vessels. Flowing blood exerts shear stress (frictional) forces on endothelial cells, and this causes them to alter the expression of many genes. We want to provide culture conditions that reflect the different endothelial environments throughout the vasculature by exposing the cells to different levels of shear stress. These cells will then be evaluated for the affect that this has on the production of FVIII.
 
Endothelial cells throughout the body are quite heterogeneous and we want to generate a number of phenotypically distinct endothelial cells that are found in large or small arteries and veins. To do this we will differentiate endothelial progenitor cells under shear stress conditions that are reflective of the conditions where these vessels are normally located.
 
This study will provide insights into how shear stress affects FVIII expression in endothelial cells and how inherent phenotypic differences between endothelial cells modify FVIII expression. Overall, we expect to advance our understanding of mechanisms that regulate FVIII expression in endothelial cells.

Use of amphipathic helical peptides coupled to nanofibrous microspheres to control hemorrhagic external bleeding in hemophiliacs


Dr. Mark Blostein
Lady Davis Institute for Medical Research
McGill University – Montreal, Quebec
Second year funding

Co-investigator:  Dr. Jake Baralet

The hereditary hemophilias are the most common inherited severe bleeding disorders and are characterized by lifelong bleeding, both spontaneous, internal bleeding as well external bleeding due to injury, most commonly from surgical procedures. The current research grant proposes to develop a new biocompatible matrix employing nanotechnology that is hemostatic by incorporating a peptide that accelerates blood coagulation and will therefore stop bleeding. This peptide was discovered in my laboratory and reduces bleeding in animal models of hemorrhage. Therefore, attaching this peptide to „nanotechnology‟ based materials has great promise as a novel agent to reduce bleeding from external hemorrhagic injuries. The methodology will include utilizing standard biochemical techniques to characterize the material followed by the testing of the biocompatible material in animal models. The development of this product is especially relevant to the goals of the Canadian Hemophilia Society by discovering new materials to control external bleeding in hemophiliacs particularly after surgical procedures.

Markers of fibrinolysis and endothelial function in adult males with hemophilia.

Lab work studentship

Ms. Kathleen De Asis
University of British Columbia
Under the supervision of Dr. Shannon Jackson
St-Paul's Hospital, Vancouver (B.C.)
Summer 2010 funding

The endothelium is a protective surface on the arteries that if disturbed can increase the risk of developing atherosclerosis and its complications including heart attacks and strokes.  Heart attack (myocardial infarction) and stroke are caused by the long term build-up of atherosclerosis (plaques of fatty material and cholesterol) and then sudden clot that occurs over a ruptured atherosclerotic plaque.  Blood flow to heart muscle or brain tissue downstream from the blockage slows or stops and the tissue suffers damage. When a heart attack or stroke occurs doctors sometimes use drugs called 'anti-fibrinolytics' in large doses to dissolve the clot and allow more blood flow to downstream tissue. 
Early studies suggest that haemophiliacs are less likely to die from heart attacks and strokes than the average person.  As part of a Canadian study  ('Risk of Ischemic Heart Disease in Hemophilia: Evaluating Endothelial Function and the Development of Atherosclerotic Vascular Disease in Hemophilia') our summer student, Kathleen De Asis, will study 3 major fibrinolytic substances using blood samples from the subjects with hemophilia enrolled to date and controls. Time permitting she may work with basic scientists to look at more novel markers in these samples.