Alan H. Lazarus

PhD

Scientist, Keenan Research Centre for Biomedical Science

Biography

My work involves learning the intricacies of the immune system in order to better understand autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, juvenile diabetes and multiple sclerosis. I am particularly focused on immune thrombocytopenia (ITP), a condition characterized by low platelets, which are particles in the blood that are important in the process of blood clotting. Disorders affecting platelets can lower the number of platelets in the blood and put patients at risk of bleeding.

I am examining IVIg, a therapeutic product that suppresses various autoimmune conditions such as ITP. IVIg is the current treatment for ITP but is very expensive, not well understood, and available only in limited supply and carries a risk of transmitting viral diseases. It also does not work well in some autoimmune diseases (e.g. SLE).

My team and I are having success in determining how IVIg suppresses ITP, and by uncovering IVIg’s mechanism of action, a replacement treatment may be developed that will be less costly, in continuous supply and free of viral disease. We have discovered a replacement for IVIg to treat some autoimmune disorders in animal models (ITP & inflammatory arthritis) and we hope to be testing new therapies in human clinical trials within the next three to five years.

Please note: Dr. Lazarus is not taking any summer students in 2018.

Recent Publications

  1. 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 .
  2. 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 .
  3. Sullivan, HC, Arthur, CM, Thompson, L, Patel, SR, Stowell, SR, Hendrickson, JE et al.. Anti-RhD reduces levels of detectable RhD antigen following anti-RhD infusion. Transfusion. 2018;58 (2):542-544. doi: 10.1111/trf.14452. PubMed PMID:29411397 .
  4. Cruz-Leal, Y, Marjoram, D, Lazarus, AH. Erythrocyte Saturation with IgG Is Required for Inducing Antibody-Mediated Immune Suppression and Impacts Both Erythrocyte Clearance and Antigen-Modulation Mechanisms. J. Immunol. 2018;200 (4):1295-1305. doi: 10.4049/jimmunol.1700874. PubMed PMID:29358275 .
  5. Mistry, N, Mazer, CD, Sled, JG, Lazarus, AH, Cahill, LS, Solish, M et al.. Red blood cell antibody-induced anemia causes differential degrees of tissue hypoxia in kidney and brain. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2018;314 (4):R611-R622. doi: 10.1152/ajpregu.00182.2017. PubMed PMID:29351418 PubMed Central PMC5966813.
  6. Marjoram, D, Cruz-Leal, Y, Bernardo, L, Le, NPL, Crispin, M, Yu, X et al.. Immunoglobulin G Fc glycans are not essential for antibody-mediated immune suppression to murine erythrocytes. Blood. 2017;130 (26):2902-2905. doi: 10.1182/blood-2017-06-793729. PubMed PMID:29109102 .
  7. Cruz-Leal, Y, Marjoram, D, Lazarus, AH. Prevention of hemolytic disease of the fetus and newborn: what have we learned from animal models?. Curr. Opin. Hematol. 2017;24 (6):536-543. doi: 10.1097/MOH.0000000000000374. PubMed PMID:28719385 .
  8. Bernardo, L, Amash, A, Marjoram, D, Lazarus, AH. Antibody-mediated immune suppression is improved when blends of anti-RBC monoclonal antibodies are used in mice. Blood. 2016;128 (8):1076-80. doi: 10.1182/blood-2016-01-692178. PubMed PMID:27330002 .
  9. Crow, AR, Lazarus, AH. Mechanistic properties of intravenous immunoglobulin in murine immune thrombocytopenia: support for FcγRIIB falls by the wayside. Semin. Hematol. 2016;53 Suppl 1 :S20-2. doi: 10.1053/j.seminhematol.2016.04.007. PubMed PMID:27312158 .
  10. Amash, A, Wang, L, Wang, Y, Bhakta, V, Fairn, GD, Hou, M et al.. CD44 Antibody Inhibition of Macrophage Phagocytosis Targets Fcγ Receptor- and Complement Receptor 3-Dependent Mechanisms. J. Immunol. 2016;196 (8):3331-40. doi: 10.4049/jimmunol.1502198. PubMed PMID:26944929 .
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Affiliations & Other Activities

  • Professor, Department of Medicine, University of Toronto
  • Professor, Laboratory Medicine & Pathobiology (cross-appointment), University of Toronto
  • Full Member, Institute of Medical Science (graduate faculty), University of Toronto
  • Scientist, Centre for Innovation, Canadian Blood Services
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