We investigate the role(s) of adhesion molecules (in particular the beta3 integrin & GPIb alpha complexes) involved in clot formation and their implications for hemostasis (incl. bleeding disorders) and thrombotic diseases (ie heart attack and stroke).
We study allo- and autoimmune diseases related to bleeding disorders such as immune thrombocytopenia (ITP) and fetal and neonatal alloimmune thrombocytopenic purpura (FNAIT).
Platelet physiology and thrombosis
Thrombotic diseases such as heart attack and stroke are the leading causes of mortality and morbidity worldwide.
We established an intravital microscopy thrombosis model at Harvard to study thrombus formation in real time in live mice.
Through direct monitoring of platelet adhesion and aggregation in vivo, we were the first to observe that platelet aggregation and thrombus formation still occur in mice lacking both fibrinogen (Fg) and von Willebrand factor (VWF).
This surprising discovery challenged the established theory of thrombosis that required Fg and VWF for thrombus formation and suggested that other unidentified molecule(s) may also be involved in thrombosis and hemostasis and may provide novel targets for anti-thrombotic therapies.
My team is in the process of identifying these mystery molecules at St. Michael's Hospital using several state-of-the-art techniques such as proteomics and confocal intravital microscopy.
Platelet immunology and maternal immune response to fetal antigens
My laboratory recently published several important papers in investigation:
- How ITP mediated by anti-beta3 integrin and anti-GPIb antibodies differ, finding that these two antibody specificities may respond to therapy differently. This has important implications for human ITP and potential screening of patients in order to successfully treat this disease.
- The first animal model of FNAIT, characterizing the disease and its response to intravenous immunoglobulin G (IVIG) therapy. Currently, the laboratory is studying the molecular and cellular basis for ITP, the maternal immune responses to fetal platelet antigens and the roles of anti-angiogenesis and apoptosis in the patho-progression of FNAIT.
Our laboratory has been well funded by both internal and external granting agencies including:
- Canadian Institutes of Health Research (CIHR)
- Heart and Stroke Foundation of Canada (HSFC, Ontario)
- Canadian Blood Services (CBS)
- Canada Foundation for Innovation (CFI)
- National Institutes of Health (NIH, USA), etc.
We are currently funded by 3 CIHR grants and several other grants from HSFC and NIH etc.