Research Program: Transplant Biology and Therapy
Professor, Department of Pediatrics, Hematology-Oncology
Section Chief, Pediatric Blood and Marrow Transplantation
Director, Center for Translational Medicine

blaza001@umn.edu
612-626-1926 — office
Preferred method of contact: Phone

Dr. Blazar's clinical profile
(University of Minnesota Physicians Web site)

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. He is the director of the Center for Translational Medicine, created to bring innovative, early phase therapies into the clinic. He 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 has served as a past chair of the National Institutes of Health Cancer Immunopathology and Immunotherapy Study Section, Food and Drug Administration Biological Response Modifiers Advisory Committee, and the Leukemia and Lymphoma Translational Research Award Committee. He is a member of the Immune Tolerance Network Executive 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 and cancer immunobiology in preclinical model systems and in the clinic. He is the author of more than 360 manuscripts, which have appeared in premier peer-reviewed publications.

Research Interests

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. Ongoing studies are testing regulatory T cells in patients undergoing hematopoietic cell
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, and those that prevent endogenous hormone induced suppression of thymopoiesis (sex steroid hormone blockade) along with cellular replacement approaches.
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. 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 and are focused upon the cell intrinsic and extrinsic properties that limit adoptive T cell efficacy.
4. Gene therapy and tissue repair. As an alternative to allotransplantation, we will use molecular strategies to correct immune and enzymatic disoders. Transposans that 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 and mesenchymal stem cells as a means of repairing tissue injuries caused by genetic and acquired disorders

Selected Publications

Steiner D, Brunicki N, Blazar BR, Bachar-Lustig E, Reisner Y. Tolerance Induction By Third Party "Off-The-Shelf" CD4+C25+ Treg Cells. Experimental Hematology 34:66-71, 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 82:23-29, 2006.

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.

Burchill MA, Yang J,Vogtenhuber C, Blazar BR, Farrar MA: Distinct roles for interleukin-2 and interleukin-15 in interleukin-2 receptor b dependent regulatory T cell development, homeostasis and function. J. Immunol 178:280-90, 2007.

Taylor PA, Ehrhardt MJ, Roforth MM, Swedin JM, Panoskaltsis-Mortari A, Serody JS, Blazar BR: Preformed Antibody, Not Primed T Cells, is the Initial and Major Barrier to Bone Marrow Engraftment in Allosensitized Recipients. Blood 109:1307-15, 2007

Min D, Panoskaltsis-Mortari A, Kuro-O M, Hollander GA, Blazar BR, Weinberg KI. Sustained thymopoiesis and improvement in functional immunity induced by exogenous KGF administration in murine models of aging. Blood. 2007 Mar 15;109(6):2529-37. Epub 2006 Nov 30.

Rossi S, Jeker L, Ueno T, Kuse S, Keller M, Zuklys S, Gudkov A, Takahama Y, Krenger W, Blazar BR, Holländer G. Keratinocyte growth factor (KGF) enhances postnatal T cell development via improvement in proliferation and function of thymic epithelial cells. Blood [epub Jan 9], 2007

Sharma MD, Baban B, Chandler P, Hou D-Y, Singh N, Yagita H, Azuma M, Blazar BR, Mellor AL, Munn DH: Dendritic cells from tumor-draining lymph nodes directly activate regulatory T cells via indoleamine 2,3-dioxygenase. J. Clin. Invest. (in press), 2007

Taylor PA, Ehrhardt MJ, Lees CJ, Tolar J, Weigel BJ, Panoskaltsis-Mortari A, Serody JS, Brinkmann V, Blazar BR. Insights into the Mechanism of FTY720 and Compatibility with Regulatory T Cells for the Inhibition of Graft-versus-Host Disease (GVHD). Blood (in press), 2007.

Weigel BJ, Panoskaltsis-Mortari A, Diers M, Lees C, Krieg AM, Chen W, Blazar BR: Dendritic Cells Pulsed or Fused with AML Cellular Antigen Provide Comparable Anti-Tumor Protective Response. Experimental Hematol. 34:1403-12, 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.

Zayed H, Xia L, Yerich A, Yant SR, Kay MA, Puttaraju M, Mansfield G, Wiest DL, McIvor RS, Tolar J, Blazar BR. Correction of severe combined immune deficiency in multipotent adult progenitor cells by spliceosome-mediated RNA trans-splicing and sleeping beauty transposon delivery. Molec. Therapy (in press), 2007.

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. 2006 May 15;107(10):4182-8. Epub 2006 Jan 12.

Serafini M, Dylla SJ, Oki M, Heremans Y, Tolar J, Jiang J, Buckley SM, Pelacho B, Burns TC, Frommer S, Rossi DJ, Bryder D, Panoskaltsis-Mortari A, O'Shaughnessy MJ, Nelson-Holte M, Fine GC, Weissman IL, Blazar BR, Verfaillie CM. Hematopoietic Reconstitution by Multipotent Adult Progenitor Cells: Precursors to Long-Term Hematopoietic Stem Cells that can be Expanded In Vitro. J. Exp. Med. 204:129-39, 2007

Tolar J, Nauta AJ, Osborn MJ, Panoskaltsis Mortari A, McElmurry RT, Bell S, Xia L, Zhou N, Riddle M, Schroeder TM, Westendorf JJ, McIvor RS, Hogendoorn PC, Szuhai K, Oseth L, Hirsch B, Yant SR, Kay MA, Peister A, Prockop DJ, Fibbe WE, Blazar BR. Sarcoma derived from cultured mesenchymal stem cells. Stem Cells. 2007 Feb;25(2):371-9. Epub 2006 Oct 12.