Alan H. Lazarus

PhD

Scientist

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.

Recent Publications

  1. Won, KD, Gil Gonzalez, L, Cruz-Leal, Y, Pavon Oro, A, Lazarus, AH. Antagonism of the Platelet-Activating Factor Pathway Mitigates Inflammatory Adverse Events Driven by Anti-erythrocyte Antibody Therapy in Mice. J Immunol. 2024;212 (10):1531-1539. doi: 10.4049/jimmunol.2300638. PubMed PMID:38506555 .
  2. Gil Gonzalez, L, Won, KD, Tawhidi, Z, Cummins, E, Cruz-Leal, Y, Tundidor Cabado, Y et al.. Human Fc gamma receptor IIIA blockade inhibits platelet destruction in a humanized murine model of ITP. Blood Adv. 2024;8 (8):1869-1879. doi: 10.1182/bloodadvances.2023012155. PubMed PMID:38330193 PubMed Central PMC11007428.
  3. Cruz-Leal, Y, Norris, PAA, Gil Gonzalez, L, Marjoram, D, Wabnitz, H, Shan, Y et al.. Trogocytosis drives red blood cell antigen loss in association with antibody-mediated immune suppression. Blood. 2024;143 (9):807-821. doi: 10.1182/blood.2023020860. PubMed PMID:37946269 .
  4. Lazarus, AH, Semple, JW. TEMRA: the CD8 subset in chronic ITP?. Blood. 2023;141 (20):2409-2410. doi: 10.1182/blood.2023019859. PubMed PMID:37200060 .
  5. Norris, PAA, Tawhidi, Z, Sachs, UJ, Cserti-Gazdewich, CM, Lin, Y, Callum, J et al.. Serum from half of patients with immune thrombocytopenia trigger macrophage phagocytosis of platelets. Blood Adv. 2023;7 (14):3561-3572. doi: 10.1182/bloodadvances.2022009423. PubMed PMID:37042934 PubMed Central PMC10368862.
  6. Roeser, A, Lazarus, AH, Mahévas, M. B cells and antibodies in refractory immune thrombocytopenia. Br J Haematol. 2023;203 (1):43-53. doi: 10.1111/bjh.18773. PubMed PMID:37002711 .
  7. Wabnitz, H, Cruz-Leal, Y, Lazarus, AH. Antigen copy number and antibody dose can determine the outcome of erythrocyte alloimmunization inducing either antibody-mediated immune suppression or enhancement in a murine model. Transfusion. 2023;63 (4):696-702. doi: 10.1111/trf.17284. PubMed PMID:36802050 .
  8. Wabnitz, H, Cruz-Leal, Y, Lazarus, AH. Antigen-specific IgG subclass composition in recipient mice can indicate the degree of red blood cell alloimmunization as well as discern between primary and secondary immunization. Transfusion. 2023;63 (3):619-628. doi: 10.1111/trf.17232. PubMed PMID:36591986 .
  9. Gil Gonzalez, L, Fernandez-Marrero, Y, Norris, PAA, Tawhidi, Z, Shan, Y, Cruz-Leal, Y et al.. THP-1 cells transduced with CD16A utilize Fcγ receptor I and III in the phagocytosis of IgG-sensitized human erythrocytes and platelets. PLoS One. 2022;17 (12):e0278365. doi: 10.1371/journal.pone.0278365. PubMed PMID:36516219 PubMed Central PMC9749970.
  10. Norris, PAA, Kaur, G, Khan, R, Zhu, G, Ni, H, Lazarus, AH et al.. Anti-inflammatory activity of CD44 antibodies in murine immune thrombocytopenia is mediated by Fcγ receptor inhibition. Blood. 2021;137 (15):2114-2124. doi: 10.1182/blood.2020009497. PubMed PMID:33662988 .
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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