Heyu Ni

MD, PhD, MSc

Platform Director, Keenan Research Centre for Biomedical Science

Biography

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 (FNAIT). 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), Canada Foundation for Innovation (CFI), and National Institutes of Health (NIH, USA), etc. We are currently funded by 3 CIHR grants and several other grants from HSFC and NIH 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 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.

Scientific Memberships:

International Society of Thrombosis and Hemostasis
American Society of Hematology
American Association of Blood Banks
Canadian Society of Atherosclerosis, Thrombosis and Vascular Biology
Canadian Society of Transfusion Medicine

Committee Membership & Grant Reviewer:

Canadian Institutes of Health Research
Natural Sciences and Engineering Research Council of Canada
Canada Foundation for Innovation
Heart and Stroke Foundation of Canada
The Kidney Foundation of Canada
China (NSFC)-Canada (CIHR) Joint Health Research Initiative – Grants Program
Alberta Heritage Foundation for Medical Research
Landsteiner Foundation for Blood Transfusion Research
National Institutes of Health
Medical Research Council, United Kingdom

Award Reviewer:

Canadian Institutes of Health Research Travel Award
Canadian Blood Services Graduate Fellowship
Ontario Graduate Scholarships in Science and Technology
Heart and Stroke/ Richard Lewar Centre of Excellence Fellowship, University of Toronto
Department of Laboratory Medicine and Pathobiology Graduate Award, University of Toronto
St. Michael’s Hosptial graduate scholarship

Journal Reviewer:

Blood
Circulation
Circulation Research
Journal of Clinical Investigation
Journal of Biological Chemistry
Journal of Thrombosis and Haemostasis
Arteriosclerosis, Thrombosis, and Vascular Biology
Thrombosis and Haemostasis
Cellular and Molecular Life Sciences
Journal of Leukocyte Biology
Thrombosis and Hemostasis
Haematologica
Hematology
Transfusion
Clinical Immunology
Experimental Hematology
European Journal of Hematology
Journal of Natural Products
British Journal of Haematology
Current Medicinal Chemistry
Apoptosis
Cardiovascular Pathology
Platelets

Recent Publications

  1. Guo, LC, Zhu, WD, Ma, XY, Ni, H, Zhong, EJ, Shao, YW et al.. Mutations of genes including DNMT3A detected by next-generation sequencing in thyroid cancer. Cancer Biol. Ther. 2018; :1-7. doi: 10.1080/15384047.2018.1523856. PubMed PMID:30252567 .
  2. Xu, XR, Wang, Y, Adili, R, Ju, L, Spring, CM, Jin, JW et al.. Apolipoprotein A-IV binds αIIbβ3 integrin and inhibits thrombosis. Nat Commun. 2018;9 (1):3608. doi: 10.1038/s41467-018-05806-0. PubMed PMID:30190457 PubMed Central PMC6127106.
  3. Brkić, J, Dunk, C, O'Brien, J, Fu, G, Nadeem, L, Wang, YL et al.. MicroRNA-218-5p Promotes Endovascular Trophoblast Differentiation and Spiral Artery Remodeling. Mol. Ther. 2018;26 (9):2189-2205. doi: 10.1016/j.ymthe.2018.07.009. PubMed PMID:30061037 PubMed Central PMC6127878.
  4. Li, J, Sullivan, JA, Ni, H. Pathophysiology of immune thrombocytopenia. Curr. Opin. Hematol. 2018;25 (5):373-381. doi: 10.1097/MOH.0000000000000447. PubMed PMID:30015642 .
  5. Guo, L, Kapur, R, Aslam, R, Hunt, K, Hou, Y, Zufferey, A et al.. Antiplatelet antibody-induced thrombocytopenia does not correlate with megakaryocyte abnormalities in murine immune thrombocytopenia. Scand. J. Immunol. 2018;88 (1):e12678. doi: 10.1111/sji.12678. PubMed PMID:29855061 .
  6. Xu, M, Li, J, Neves, MAD, Zhu, G, Carrim, N, Yu, R et al.. GPIbα is required for platelet-mediated hepatic thrombopoietin generation. Blood. 2018;132 (6):622-634. doi: 10.1182/blood-2017-12-820779. PubMed PMID:29794068 .
  7. Qu, M, Liu, Q, Zhao, HG, Peng, J, Ni, H, Hou, M et al.. Low platelet count as risk factor for infections in patients with primary immune thrombocytopenia: a retrospective evaluation. Ann. Hematol. 2018;97 (9):1701-1706. doi: 10.1007/s00277-018-3367-9. PubMed PMID:29777278 PubMed Central PMC6097778.
  8. Wan, H, Wang, Y, Ai, J, Brathwaite, S, Ni, H, Macdonald, RL et al.. Role of von Willebrand factor and ADAMTS-13 in early brain injury after experimental subarachnoid hemorrhage. J. Thromb. Haemost. 2018;16 (7):1413-1422. doi: 10.1111/jth.14136. PubMed PMID:29729651 PubMed Central PMC6055612.
  9. Xu, XR, Yousef, GM, Ni, H. Cancer and platelet crosstalk: opportunities and challenges for aspirin and other antiplatelet agents. Blood. 2018;131 (16):1777-1789. doi: 10.1182/blood-2017-05-743187. PubMed PMID:29519806 .
  10. Butz, H, Ding, Q, Nofech-Mozes, R, Lichner, Z, Ni, H, Yousef, GM et al.. Elucidating mechanisms of sunitinib resistance in renal cancer: an integrated pathological-molecular analysis. Oncotarget. 2018;9 (4):4661-4674. doi: 10.18632/oncotarget.23163. PubMed PMID:29435133 PubMed Central PMC5797004.
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Affiliations & Other Activities

  • Scientist, Keenan Research Centre for Biomedical Science, St. Michael’s Hospital
  • Professor, Department of Laboratory Medicine and Pathobiology, University of Toronto
  • Professor, Department of Medicine, University of Toronto
  • Professor, Department of Physiology, University of Toronto
  • Scientist, Canadian Blood Services Centre for Innovovation Platform
  • Director for Hematology, Cancer and Immunological Diseases
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