CHS Research Grants for 2011

Dr. Christine Hough
Dept. of Pathology and Molecular Medicine
Queen's University
Second 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.

Dr. Andrea Doria
Diagnostic and Imaging Department
The Hospital for Sick Children - Toronto, Ontario
First year funding

Co-investigators: Dr. Aaron Fenster; Dr. Marshall Sussman; Dr. Victor Blanchette

Hemophilia is an inherited bleeding disorder characterized by the lack of coagulation factors which results in an inability to control bleeding into joints, leading to long-term joint damage. Prophylaxis, reduces the joint symptoms and avoids further degeneration of the joints, however it should be started prior to the development of cartilage lesions. Repeated extravazation of blood into the joint cavity is the factor responsible for cartilage degeneration in hemophilic arthropathy. Microstructural cartilage changes are thought to precede macroscopic cartilage lesions [8] which are responsible for most of the morbidity of hemophilic arthropathy. Conventional imaging techniques are unable to visualize early soft tissue and cartilage changes. Evaluation of soft tissue changes and microstructural cartilage changes with sensitive imaging tools may direct clinical management and prophylaxis towards avoiding further irreversible macroscopic osteochondral damage. New functional MRI techniques and 3DUS anatomic imaging may be able to diagnose early joint changes at a time where treatment is still effective to avoid further degeneration of the joint. No prior studies have investigated the imaging of very early structural and physiologic events in hemophilic joints. We will pioneer the development of novel imaging techniques for assessment of early soft tissue and cartilage changes in hemophiliacs.

Lab work studentship

Ms. Ashley Warias
McMAster University

Under the direct supervision of Dr Vicky Breakey & indirect supervision of Dr V. Blanchette
The Hospital for Sick Children, Toronto
Summer 2011 funding

Transition is a difficult time for adolescents with hemophilia.  We are in the process of completing an Internet-based education program for adolescents with hemophilia.  “Teens Taking Charge: Managing Hemophilia Online” will provide teens with eight modules of learning and help them to build self-management skills prior to transition to adult care.  As a key part of our evaluation of this program, we will use validated tools that are hemophilia-specific.  Our assessment of the website will include determination of quality of life, self-efficacy and stress.  We will also see if teens gain knowledge and are satisfied with the program.  The Health Education Intervention Questionnaire (HEI-Q, Osborne et al. 2007) is a suitable tool to assess the impact of the program, but has not yet been validated in adolescents. We aim to validate the HEI-Q in teens with hemophilia.  This process will include clinical adaption of the language of the survey tool as needed, consensus discussion with investigators, cognitive testing with teens, revisions as needed, application in the field and psychometric evaluations. Ms Warias will be involved in the cognitive testing and revisions of the tool.  If there is time, she will begin the process of application in the field; if not, this will be completed by a clinical research assistant.

Lab work studentship

Mr. Kuan-Chieh (Jackson) Wang
University of Toronto

Under the supervision of Dr Andrea Doris
The Hospital for Sick Children, Toronto
Summer 2011 funding

Bleeding inside the body causes many troubles. Blood might build up in joints and cause extreme pain which prevents the patients to do normal physical activities. This leads to a decrease in bone quality. For children, it reduces the quality of life and may affect their growth. We will try to establish the reliability of quatitative ultrasound which is a diagnostic tool that can be easily used to monitor children's bone.