Heyu Ni

Dr. Ni has had a long-term outstanding research program in Platelets and Thrombosis, investigating platelet physiology and immunology to develop new treatments for clotting disorders, alloimmune and autoimmune disorders; his particular focus in investigation of the adhesion molecules that are involved in clot formation. His research into autoimmune thrombocytopenia (ITP), fetal and neonatal alloimmune thrombocytopenia (FNAIT), as well as the role of fibrinogenindependent platelet aggregation in clotting are important contributions to medical science and transfusion medicine. He is utilizing these advances to develop new therapeutic strategies for such disorders.

He is also an accomplished educator with many graduate and post-doctorate students being mentored through his laboratory.

Research Synopsis

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:

1. 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.
2. 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.

Selected Publications

Shen C, Liu M, Xu R, Wang G, Li J, Chen P, Ma W, Mwangi J, Lu Q, Duan Z, Zhang Z, Dahmani FZ, Mackeigan DT, Ni H, Lai R. (2020). 14-3-3ζ-c-Src-integrin-β3 complex is vital for platelet activation. Blood . August 2020. 135: 1-41. 

Xiaohong Ruby Xu, Yiming Wang, Reheman Adili, Lining Ju, Christopher M. Spring, Joseph Wuxun Jin, Hong Yang, Miguel A.D. Neves, Pingguo Chen, Yan Yang, Xi Lei, Yunfeng Chen, Hailong Zhang, Jina Song, Peifeng Ke, Dan Zhang, Naadiya Carrim, Guangheng Zhu, Yi-Min She, Terry Cyr, Wenbin Fu, Guoqing Liu, Philip W. Connelly, Margaret L. Rand, Khosrow Adeli, John Freedman, Jeffrey E. Lee, Patrick Tso, Patrizia Marchese, W. Sean Davidson, Shaun P. Jackson, Cheng Zhu, Zaverio M. Ruggeri, and Heyu Ni. Apolipoprotein A-IV is a novel ligand of platelet b3 integrins and an endogenous inhibitor of thrombosis. Nature Communications. Sept. 6, 2018

Xu M, Li J, Neves MAD, Zhu G, Carrim N, Yu R, Gupta S, Marshall J, Rotstein O, Peng J, Hou M, Kunishima S, Ware J, Branch DR, Lazarus A, Ruggeri ZM, Freedman J, Ni H. GPIbα is required for platelet-mediated hepatic thrombopoietin generation. Blood. 2018 Aug 9;132(6):622-634; published with an editorial commentary. 

Xiaohong Ruby Xu, George Yousef, Heyu Ni. Cancer and Platelet Crosstalks: Opportunities and challenges for aspirin and other anti-platelet agents. Blood. 2018 Apr 19;131(16):1777-1789. 

Issaka Yougbaré, Wei-She Tai, Darko Zdravic, Brigitta Elaine Oswald, Sean Lang, Guangheng Zhu, Howard Leong-Poi, Qu Dawei, Yu Lisa, Caroline Dunk, Jianhong Zhang, John G. Sled, Stephen J. Lye, Jelena Brkić, Chun Peng, Petter Höglund, B. Anne Croy, S. Lee Adamson, Xiao-Yan Wen, Duncan J. Stewart, John Freedman, and Heyu Ni. Activated NK cells cause placental dysfunction and miscarriages in fetal alloimmune thrombocytopenia. Nature Communications. 2017 Aug 9;8(1):224. 

Guangheng Zhu, Qing Zhang, Emily C. Reddy, Naadiya Carrim, Yunfeng Chen, Xiaohong Ruby Xu, Miao Xu, Yiming Wang, Yan Hou, Li Ma, Yan Li, Min Rui, Tania Petruzziello, Christopher Lavalle, Tyler W. Stratton, Xi Lei, Adili Reheman, Pingguo Chen, Cheng Zhu, John A. Wilkins, Richard O. Hynes, John Freedman, Heyu Ni. (2016). Integrin PSI domain has endogenous thiol isomerase function and is a novel target for anti-platelet therapy. Blood. 2017 Mar 30;129(13):1840-1854.

Lili Tao, Qingshu Zeng, June Li, Miao Xu, Jiajia Wang, Ying Pan, Huiping Wang, Qianshan Tao, Yang Chen, Jun Peng, Ming Hou, Arend Jan Gerard Jansen, Heyu Ni, Zhimin Zhai. Journal of Hematology and Oncology. 2017 Feb 8, DOI: 10.1186/s13045-017-0413-3. 

Yougbaré I, Lang S, Yang H, Chen P, Zhao X, Tai WS, Zdravic D, Vadasz B, Li C, Piran S, Marshall A, Zhu G, Tiller H, Killie MK, Boyd S, Leong-Poi H, Wen XY, Skogen B, Adamson SL, Freedman J, Ni H. Maternal anti-platelet β3 integrins impair angiogenesis and cause intracranial hemorrhage. J Clin Invest. 2015 Apr 1;125(4):1545-56.

Reheman A, Xu X, Reddy EC, Ni H. Targeting activated platelets and fibrinolysis: hitting two birds with one stone. Circ Res. 2014;114(7): 1070-3.

Wang Y, Reheman A, Spring CM, Kalantari J, Marshall AH, Wolberg AS, Gross PL, Weitz JI, Rand ML, Mosher DF, Freedman J, Ni H. Plasma fibronectin supports hemostasis and regulates thrombosis. J Clin Invest. 2014 Oct 1;124(10):4281-93.

Murphy AJ, Bijl N, Yvan-Charvet L, Welch CB, Bhagwat N, Reheman A, Wang Y, Shaw JA, Levine RL, Ni H, Tall AR, Wang N. Cholesterol efflux in megakaryocyte progenitors suppresses platelet production and thrombocytosis. Nat Med. 2013 May;19(5):586-94

Honours and Awards

LMP Richard G. Hegele Award for Excellence in Research and Innovation, University of Toronto (2022)

2021 Distinguished Lecturer / Scientific Excellence Award in Blood and Blood Vessel Sciences

Awarded by the Canadian Society of Atherosclerosis, Thrombosis and Vascular Biology (CSATVB) and the CIHR Institute of Circulatory and Respiratory Health (CIHR-ICRH)

Fellow of the Canadian Academy of Health Sciences (CAHS) (2020)