Heyu Ni,

• Platelet, Immunology
• Adhesion Molecules
• Thrombosis, Hemostasis
• Intravital Microscopy

My laboratory currently investigates the role(s) of adhesion molecules (in particular the beta3 integrin and GPIb alpha complexes) involved in clot formation as well as their implications for hemostasis (including bleeding disorders) and thrombotic diseases (ie. heart attack and stroke). The laboratory also studies allo- and autoimmune diseases related to bleeding disorders such as immune thrombocytopenia (ITP) and fetal and neonatal alloimmune thrombocytopenic purpura (FNAITP). These studies have been well funded by both internal and external granting agencies including Canadian Institutes of Health Research (CIHR), Heart and Stroke Foundation of Canada (HSFC), Canadian Blood Services (CBS) and Canada Foundation for Innovation (CFI), etc.

Platelet physiology and thrombosis: thrombotic diseases such as heart attack and stroke are the leading causes of mortality and mobility 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 von Willebrand factor (VWF) and fibrinogen (Fg). This surprising discovery challenged the established theory of thrombosis that required VWF and Fg 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 two important papers in blood investigation: 1) How ITP mediated by anti-3 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. 2) The first animal model of FNAITP, 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 FNAITP.

Selected Publications:

Heyu Ni, Peter Yuen, Jessie M. Papalia, Takao Sakai, Jane Trevithick, Reinhard Fässler, Richard O. Hynes, Denisa D. Wagner. Plasma fibronectin promotes thrombus growth in injured arterioles. Proceedings of the National Academy of Sciences of USA. 2003, 100(5): 2415-2419.

Heyu Ni, Jessie M. Papalia, Jay L. Degen and Denisa D. Wagner. Control of Thrombus Embolization and Fibronectin Internalization by Integrin aIIbß3 Engagement of the Fibrinogen Gamma Chain.. Blood. 2003 Nov 15, 102(10): 3609-3614; Editorial commentary: 2003, 102 (10): 3461.

Adili Reheman, Peter Gross, Hong Yang, Pingguo Chen, David Allen, Valery Leytin, John Freedman, Heyu Ni. Vitronectin Stabilizes Thrombi and Vessel Occlusion but Plays A Dual Role in Platelet Aggregation. Journal of Thrombosis and Haemostasis. 2005, 3:875-883; Editorial commentary. 2005 May; 3: 873-874

Heyu Ni, Pingguo Chen, Christopher M. Spring, Ebrahim Sayeh, John W. Semple, Alan H. Lazarus, Richard O. Hynes, John Freedman. A novel murine model of fetal and neonatal alloimmune thrombocytopenia: Response to intravenous IgG therapy. Blood. 2006, 107 (7): 2976-2983.

Michelle Webster, Ebrahim Sayeh, Min Crow, Pingguo Chen, Bernhard Nieswandt, John Freedman and Heyu Ni. Relative efficacy of IVIG in ameliorating thrombocytopenia induced by anti-platelet GPIIbIIIa versus GPIba antibodies. Blood. 2006, 108(3):943-6.

Hong Yang, Adili Reheman, Pingguo Chen, Richard O. Hynes, John Freedman, Denisa D. Wagner, Heyu Ni. Fibrinogen and von Willebrand factor-independent platelet aggregation in vitro and in vivo. Journal of Thrombosis and Haemostasis. 2006, 4: 2230-37

Adili Reheman, Hong Yang, Guangheng Zhu, Wuxun Jin, Feng He, Christopher M. Spring, Xufang Bai, Peter L. Gross, John Freedman , and Heyu Ni. Plasma fibronectin depletion enhances platelet aggregation and thrombus formation in mice lacking fibrinogen and von Willebrand factor. Blood. 2009; 113: 1809-1817

Hong Yang, Sean Lang, Zhimin Zhai, Ling Li, Walter H.A. Kahr, Pingguo Chen, Jelena Brkic, Christopher M. Spring, Matthew J. Flick, Jay L. Degen, John Freedman and Heyu Ni*. Fibrinogen is required for maintenance of platelet intracellular and cell surface P-selectin expression. Blood. 2009, 114: 425-436. Editorial commentary: 2009; July 9. 114: 234