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. 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; :. doi: 10.1111/trf.17284. PubMed PMID:36802050 .
  2. 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 .
  3. 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.
  4. 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 .
  5. Cruz-Leal, Y, Lazarus, AH. Could antigen loss be a potential mechanism to explain antibody-mediated immune suppression?. Transfusion. 2021;61 (4):1004-1006. doi: 10.1111/trf.16309. PubMed PMID:33624837 .
  6. Norris, PAA, Kaur, G, Lazarus, AH. New insights into IVIg mechanisms and alternatives in autoimmune and inflammatory diseases. Curr Opin Hematol. 2020;27 (6):392-398. doi: 10.1097/MOH.0000000000000609. PubMed PMID:32868670 .
  7. Khan, R, Menard, M, Jen, CC, Chen, X, Norris, PAA, Lazarus, AH et al.. Inhibition of platelet phagocytosis as an in vitro predictor for therapeutic potential of RBC antibodies in murine ITP. Blood. 2020;135 (26):2420-2424. doi: 10.1182/blood.2019003646. PubMed PMID:32374819 .
  8. Norris, PAA, Segel, GB, Burack, WR, Sachs, UJ, Lissenberg-Thunnissen, SN, Vidarsson, G et al.. FcγRI and FcγRIII on splenic macrophages mediate phagocytosis of anti-glycoprotein IIb/IIIa autoantibody-opsonized platelets in immune thrombocytopenia. Haematologica. 2021;106 (1):250-254. doi: 10.3324/haematol.2020.248385. PubMed PMID:32107327 PubMed Central PMC7776240.
  9. Wabnitz, H, Khan, R, Lazarus, AH. The use of IVIg in fetal and neonatal alloimmune thrombocytopenia- Principles and mechanisms. Transfus Apher Sci. 2020;59 (1):102710. doi: 10.1016/j.transci.2019.102710. PubMed PMID:31926738 .
  10. Crow, AR, Kapur, R, Koernig, S, Campbell, IK, Jen, CC, Mott, PJ et al.. Treating murine inflammatory diseases with an anti-erythrocyte antibody. Sci Transl Med. 2019;11 (506):. doi: 10.1126/scitranslmed.aau8217. PubMed PMID:31434758 .
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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