Alan Lazarus
PhD
Dr Lazarus obtained his PhD in Microbiology and Immunology at McGill University.
His affiliations are:
- Scientist in the Keenan Research Centre of the Li Ka Shing Knowledge Institute of St. Michael's Hospital
- Scientist, Research and Development, Canadian Blood Services
- Professor, Medicine, University of Toronto
- Professor, Laboratory Medicine & Pathobiology, University of Toronto
- Full Member, Institute of Medical Science, University of Toronto
Research Synopsis
My research is understanding how therapeutic antibodies can be used to treat autoimmune disease.
We study the ability of novel monoclonal antibodies, as well as antibodies taken from the plasma of healthy blood donors (IVIg) to inhibit disease progression in autoimmunity.
We also study how an antibody called "anti-D" is able to prevent haemolytic disease of the fetus and newborn.
Intravenous immunoglobulin (IVIg) is a blood product derived from the plasma of healthy blood donors and has been used for more than 25 years to treat a number of different autoimmune diseases.
Although the exact mechanism of action of IVIg has remained elusive, work from our laboratory has taken aim at developing a good understanding as to how IVIg successfully treats autoimmunity.
Two diseases that we study include:
- an autoimmune disease to platelets called immune thrombocytopenia (ITP)
- a murine model of rheumatoid arthritis.
We have found that specific monoclonal antibodies can replace IVIg in the treatment of autoimmune disease and we are studying these antibodies.
Potential graduate students can work on the discovery of new monoclonal antibodies to treat autoimmune disease as well as work on understanding mechanisms of action of some of the antibodies which we have recently discovered in our laboratory.
Hemolytic disease of the fetus and newborn (HDFN) is a very severe disease that can occur if a mother who does not express the "rhesus D antigen (RhD)" on her red blood cells becomes pregnant with a RhD-positive child.
HDFN can be effectively avoided in these situations by administration of an antibody derived from the plasma of blood donors called anti-D. In fact, the routine administration of anti-D to rhesus D-negative mothers pregnant with a D-positive child is one of the most powerful applications of antibody-based immunotherapy for a human disease.
Unfortunately, we do not know how anti-D prevents HDFN! We are studying how anti-D prevents HDFN (in murine models) and attempting to come up with a recombinant product to avoid injecting healthy mothers with a blood-product (anti-D) that is taken from the plasma of thousands of blood-donors.
Potential graduate students can work on how antibodies with anti-D-like properties can inhibit the immune response to red blood cells as well as work on helping us find new antibodies to prevent immunization to red blood cells.
Selected Publications
A monoclonal antibody with anti-D-like activity in murine immune thrombocytopenia requires Fc domain function for immune thrombocytopenia ameliorative effects. Yu X, Menard M, Seabright G, Crispin M, Lazarus AH. Transfusion. 2015 Mar 6. doi: 10.1111/trf.13032. PMID:25752470
CD44 antibody-mediated amelioration of murine immune thrombocytopenia (ITP): mouse background determines the effect of FcγRIIb genetic disruption. Crow AR, Amash A, Lazarus AH. Transfusion. 2014 Dec 15. doi: 10.1111/trf.12957. PMID:25496771
RhD Specific Antibodies Are Not Detectable in HLA-DRB1(*)1501 Mice Challenged with Human RhD Positive Erythrocytes. Bernardo L, Denomme GA, Shah K, Lazarus AH. Adv Hematol. 2014;2014:470242.
Antibody-mediated immune suppression of erythrocyte alloimmunization can occur independently from red cell clearance or epitope masking in a murine model. Yu H, Stowell SR, Bernardo L, Hendrickson JE, Zimring JC, Amash A, Uchikawa M,Lazarus AH. J Immunol. 2014 Sep 15;193(6):2902-10
Therapeutic effect of IVIG on inflammatory arthritis in mice is dependent on the Fc portion and independent of sialylation or basophils. Campbell IK, Miescher S, Branch DR, Mott PJ, Lazarus AH, Han D, Maraskovsky E, Zuercher AW, Neschadim A, Leontyev D, McKenzie BS, Käsermann F. J Immunol. 2014 Jun 1;192(11):5031-8.
Allogeneic platelet transfusions prevent murine T-cell-mediated immune thrombocytopenia. Guo L, Yang L, Speck ER, Aslam R, Kim M, McKenzie CG, Lazarus AH, Ni H, Hou M, Freedman J, Semple JW. Blood. 2014 Jan 16;123(3):422-7.
Amelioration of murine passive immune thrombocytopenia by IVIg and a therapeutic monoclonal CD44 antibody does not require the Myd88 signaling pathway. Crow AR, Yu H, Han D, Lazarus AH. PLoS One. 2013 Aug 5;8(8):e71882.
Monoclonal versus polyclonal anti-D in the treatment of ITP. Lazarus AH. Expert Opin Biol Ther. 2013 Oct;13(10):1353-6.
CD44 antibodies and immune thrombocytopenia in the amelioration of murine inflammatory arthritis. Mott PJ, Lazarus AH. PLoS One. 2013 Jun 13;8(6):e65805.
Antibody specific for the glycophorin A complex mediates intravenous immune globulin-resistant anemia in a murine model. Chen X, Ghaffar H, Jen CC, Lazarus AH. Transfusion. 2014 Mar;54(3):655-64.