Professor
Section Chief Pediatric Blood and Marrow Transplantation
Mayo Mail Code 109
420 Delaware St. SE
Minneapolis, MN 55455
Phone: (612) 626-1926
Fax: (612) 624-3913
blaza001@umn.edu
Preferred method of contact: Phone
Dr. Blazar is a Professor of Pediatrics in the Division of Hematology-Oncology and Blood and Marrow Transplantation and attends on the Pediatric Blood and Marrow Transplantation (BMT) service. Dr. Blazar is the recipient of the Andersen Chair in Transplantation Immunology to recognize his pioneering work in the development of novel immune-based therapies.
Dr. Blazar received his M.D. from Albany Medical College. He completed a residency in Pediatrics and a fellowship in hematology/oncology and bone marrow transplantation at the University of Minnesota. Dr. Blazar joined the University of Minnesota faculty in 1985. He is board certified in Pediatrics and Hematology/Oncology.
Dr. Blazar serves as Chair of the National Institutes of Health Cancer Immunopathology and Immunotherapy Study Section and as a member of the Immune Tolerance Network Executive Committee, Food and Drug Administration Biological Response Modifiers Advisory Committee, and Leukemia and Lymphoma Translational Research Award Committee. Dr. Blazar is the recipient of an NIH MERIT Award and is the principal investigator of several other NIH funded studies focusing on BMT immunological studies. Dr. Blazar is the author of more than 300 manuscripts which have appeared in premier peer-reviewed publications.
Honors and Awards
1. Prevention of graft-versus-host disease (GVHD).
We developed new approaches to propagate and expand CD4+25+ T regulatory cells that can suppress alloresponses after in vivo adoptive transfer and have isolated novel populations that have more potent regulatory/suppressor cell activity. In other studies, we have developed an ex vivo induction of tolerance as a means of preventing GVHD. We have analyzed the biochemical events associated with tolerance induction and have applied these findings to the development of new approaches to induce tolerance via the use of inhibitors of signal transduction or cell cycle progression. Such methodologies are being applied to the analysis of CD4+25+ T regulatory cells.
2. Development of new strategies to enhance immune recovery after transplantation.
Because GVHD and the conditioning regimens used for bone marrow transplantation induce severe thymic injury, we also are exploring novel approaches to protect the thymic epithelial cells (TEC) against injury including the use of cytokines that stimulate TEC proliferation/repair (keratinocyte growth factor), agents that protect against genotoxic stress (p53 inhibitors), and those that prevent endogenous hormone induced suppression of thymopoiesis (sex steroid hormone blockade).
3. Prevention of tumor/leukemia relapse.
Projects are ongoing to utilize dendritic cell hybrid fusion vaccines as a means of inducing anti-leukemia immune responses in vivo. Adoptive T cell immunotherapy is being utilized alone, in conjunction with dendritic cell fusion vaccines, or via the use of tumor antigens associated with gp96 heat shock proteins. For adoptive immunotherapy, we have developed new approaches to simultaneously track green fluorescent cytotoxic lymphocytes that are generated in vitro against leukemia cells and tumor cells.
4. Gene therapy and tissue repair.
As an alternative to allotransplantation, we will use molecular strategies to correct immune and enzymatic disoders. Transposans or DNA oligonucleotides are being tested. Both reporter gene constructs and disease correction constructs are being tested in murine models and in murine models in which human cord blood cells are given. In addition, we are infusing murine multipotent adult progenitor cells as a means of repairing tissue injuries caused by genetic and acquired disorders.
Bibliography (selected from >300 manuscripts)
Barao I, Hanash AM, Welniak L, Sun K, Blazar BR, Levy R, Murphy WJ: Suppression of NK-cell mediated bone marrow rejection by regulatory T cells: Linking adaptive to innate responses. Proc. Natl. Acad. Sci. USA (Track II) 103:5460-5, 2006.
Porter SB, Liu B, Rogosheske J, Levine B, June C, Wagner J, Miller JS, Blazar BR: Effects of graft-versus-host disease prophylactic agents on umbilical cord blood derived human CD4+CD25+ T-regulatory cells and CD4+25- T-cells expansion and function. Transplantation (in press), 2006.
Huang X, Wilber A, Bao L, Tuong D, Orchard PJ, McIvor RS, Blazar BR, Zhou X: Stable gene transfer and expression in human primary T lymphocytes by Sleeping Beauty transposon system. Blood 107:483-91, 2006.
Zayed H, McIvor RS, Wiest DL, Blazar BR: In Vitro Functional Correction of the Mutation Responsible for Murine Severe Combined Immune Deficiency by Short Fragment Homologous Recombination. Human Gene Therapy 17:158-66, 2006.
Tolar J, O’Shaughnessy MJ, Panoskaltsis-Mortari A, McElmurry RT, Bell S, Riddle M, McIvor RS, Yant SR, Kay MA, Krause D, Verfaillie CM, Blazar BR. Host Factors that Impact the Biodistribution and Persistence of Multipotent Adult Progenitor Cells. Blood (in press), 2006
Li L, Godfrey WR, Porter SB, Ge Y, June CH, Blazar BR, Boussiotis VA: CD4+25+ regulatory T cells from human cord blood have molecular profiles of T cell anergy. Blood 106:3068-73, 2005.
Sun K, Welniak LA, Panoskaltsis-Mortari A, O'Shaughnessy MJ, Liu H, Barao I, Riordan W, Sitcheran R, Wysocki C, Serody JS, Blazar BR, Sayers TJ, Murphy WJ. Inhibition of acute graft-versus-host disease with retention of graft-versus-tumor effects by the proteasome inhibitor bortezomib. Proc Natl Acad Sci U S A. 2004 May 25;101(21):8120-5
Moseman EA, Dawson AJ, Liang X, Panoskaltsis-Mortari A, Krieg AM, Liu Y-J, Blazar BR, Chen W: Generation of CD4+CD25+ regulatory T cells by CpG oligodeoxynucleotide-activated human plasmacytoid dendritic cells. J. Immunol 173:4433-4442, 2004
Godfrey WR, Spoden DJ, Ge YG, Baker SR, Lin B, Levine BL, June CH, Blazar BR, Porter SB: FoxP3 protein expressing cord blood CD4+25+ derived T regulatory cell lines manifest potent suppressor cells activity. Blood 105:750-8, 2005.
Taylor PA, Panoskaltsis-Mortari A, Freeman GJ, Sharpe AH, Noelle RJ, Rudensky AY, Mak TW, Serody JS, Blazar BR: Targeting of Inducible Costimulator (ICOS) Expressed on Alloreactive T cells Downregulates Graft-versus-Host Disease (GVHD) and Facilitates Engraftment of Allogeneic Bone Marrow (BM). Blood 105:3372-80, 2005.
Taylor PA, Panoskaltsis-Mortari A, Swedin JM, Lucas PJ, Gress RE, Levine BL, June CH, Serody JS,Blazar BR: L-Selectin(hi) but not the L-selectin(lo) CD4+25+ T-regulatory cells are potent inhibitors of GVHD and BM graft rejection. Blood 104:3804-12, 2004.
Godfrey WR, Spoden DJ, Ge Y, Levine BL, June CH, Blazar BR, Porter SB. In Vitro Expanded Human CD4+CD25+ T Regulatory Cells Markedly Inhibit Allogeneic Dendritic Cell Stimulated MLR Cultures. Blood 104: 453-461, 2004.
Chen W, Antonenko S, Sederstrom JM, Liang X, Chan ASH, Kanzler H, Blom B, Blazar BR, Liu Y-J: Thrombopoietin cooperates with flt3-ligand in the generation of large numbers of plasmacytoid dendritic cell precursors from human hematopoietic progenitors. Blood 103:2547-53, 2004.
Godfrey WR, Krampf M, Taylor PA, Blazar BR: Ex vivo depletion of alloreactive cells based on CFSE dye dilution, activation antigen selection, and dendritic cell stimulation. Blood 103:1158-1165, 2004.