Three Centre for Blood Research (CBR) principal investigators received funding from the Canadian Institutes of Health Research (CIHR), as part of the CIHR Fall 2021 Project Grant competition.
Drs. Kelly Brown, Ed Pryzdial and Natalie Strynadka have been funded on projects. In total, UBC researchers are leading 48 projects awarded Project Grants totaling $34.7 million. A further 13 UBC-led projects were awarded priority announcement grants totaling $1.3 million. The Project Grant program funds projects with the potential to advance health-related fundamental or applied knowledge, health research, health care, health systems, and/or health outcomes.
From studying vasculitis in children to better understanding viral infection and drug-resistant bacteria, these CBR scientists and their teams seek to answer crucial health-related questions. Congratulations to all!
Evaluating the utility of adult-defined prognostic biomarkers: Are they appropriate in childhood onset primary chronic vasculitis?
Principal Investigator: Kelly Brown, Department of Pediatrics
Co-PIs: David Allan Cabral, Department of Pediatrics
Co-investigator(s): Cherry Mammen, Kimberly Morishita
Amount: $290,700 over 2 years
Vasculitis is a rare disease in children and adults that develops when blood vessels carrying oxygen to critical organs in the body become inflamed. In children with vasculitis, the kidney is one of the organs where the blood vessels are most commonly affected, but it can also affect the lungs, eyes, brain or skin. If organ damage is severe, the child may die or suffer permanent organ damage. Since vasculitis is less common in children than adults, most of what we understand for children with the disease, and how to treat it, comes from experience with adults. Current treatment involves drugs used for cancer patients. These treatments can be life-saving, but they do not prevent the disease from returning and they have serious side effects such as infections, cancer, difficulty having children, and heart disease. Finding the right drug at the right dose for each patient can be a tedious process of stopping and starting treatment, and repeatedly taking a small sample of affected organs with a small surgical procedure (biopsy) – this is not always feasible, especially for children. Doctors treating adults with vasculitis have found that ‘markers’ in blood or urine may tell them which patients have a higher risk of recurring disease and/or more severe disease in the kidneys. It is not clear if these markers are present in children, and if so, if they work in the same way. While their bodies (and immune system) are still growing, children may respond differently to the disease and treatments compared to adults. Our team created the largest international network of doctors and scientists in the world studying vasculitis in children. In this project, we will use collected information and samples from over 300 pediatric patients to check if the adult markers are present and if they predict risks in children. If so, they will provide doctors with tools to “personalise” treatment for each child.
Host cell-derived tissue factor as a broad-spectrum basis for viral pathology and infection
Principal Investigator: Edward Pryzdial, Department of Pathology and Laboratory Medicine
Co-PIs: Marc S Horwitz
Amount: $1,137,645 over 5 years
Well-balanced blood clotting is essential for health and has life-threatening impact when tipped off-balance. Many viruses are known to trigger an infected person’s blood clotting system and cause a wide range of clotting-related clinical problems; from heart disease to bleeding. The processes used by the virus to cause these diseases are poorly understood. Using the oral herpes virus (HSV1) as a model virus, our lab has shown that these germs hijack clotting activators to increase infection. To understand how, the current proposal focuses on our discovery that a protein called, tissue factor, is integrated into the virus’ surface. Tissue factor is found within our cell membranes and is essential for life. Many viruses are covered with a membrane, called an envelope, which is acquired from our infected cells and can therefore contain tissue factor. Why is tissue factor important? Because it is the initiator of blood clotting and it also alters the function of cells. Here we propose to expand our findings in HSV1 and extend our knowledge to HIV and dengue virus, both major global problems. We will take biochemical and animal approaches to test our ideas, which have already revealed possible strategies to treat these virus infections. In addition to these viruses, many others that burden healthcare systems world-wide have an envelope, such as influenza, Ebola, hepatitis C and Zika viruses. The five virus types we have investigated to date all have tissue factor, suggesting that any virus with an envelope can acquire tissue factor. Since cells containing tissue factor are found throughout the body and are infected by many types of virus, we anticipate that targeting tissue factor found on the surface of viruses will allow us to treat a wide-range of viral infections and fill a serious deficiency in global healthcare.
Structure-guided in vitro and in situ analysis of virulence linked secretion systems in drug-resistant bacteria*
Principal Investigator: Natalie Strynadka, Department of Biochemistry and Molecular Biology
*Conditionally funded at time of posting