Bruce Blazar, MD
Pediatric Hematologist Oncologist
Albany Medical College
Pediatrics, University of Minnesota
Hematology/Oncology and Bone Marrow Transplantation, University of Minnesota
425 E River Rd
Minneapolis, MN 55455
MMC 366 Mayo
8366A (Campus Delivery Code)
420 Delaware St SE
Minneapolis, MN 55455
Dr. Blazar is a Professor of Pediatrics in the Division of 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 500 manuscripts which have appeared in premier peer-reviewed publications.
Dr. Blazar's laboratory is focused upon the immunobiology of transplantation. There are five basic project areas:
1. Graft-versus-host disease (GVHD). GVHD is a multi-organ system disorder in which donor T cells recognize host alloantigens present on antigen-presenting cells and tissues in the context of an inflammatory response. Studies are directed toward identifying and modifying signals that drive or inhibit acute and chronic GVHD generation. These include the analysis of positive costimulatory molecules and negative regulators of the immune response that counterbalance positive costimulation as well as intracellular signaling and metabolic pathways along with pro- and anti-inflammatory cytokines that regulate these responses at the level of the GVHD target organ. 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. We are also examining cell based therapies such as regulatory T cells (see below) and myeloid-derived suppressor cells. We have also used a newly developed model of chronic GVHD that results from T:B cooperativity, leading to alloantibody and subsequently, collagen deposition, culminating in multi-organ system injury and pulmonary and liver fibrosis.
2. Regulatory T cells. We have developed new approaches to propagate and expand CD4+25+ T regulatory cells that can suppress alloresponses and GVHD . We are analyzing the biochemical, molecular, cytokine and cell surface factors that regulate murine and human CD4+25+ T cell development, expansion and function in vitro and in vivo. We are also investigating how CD4+25+ T cells affect hematopoiesis and immune function in mice including models of human lymphohematopoiesis.The in vivo biological effects of our immune manipulations are being monitored using whole-body imaging techniques to track donor effector or regulatory T cells using transgenic mice expressing green fluorescent protein and firefly luciferase. Some of these studies have been translated into the clinic.
3. Immune post-transplant. Because GVHD and the conditioning regimens used for bone marrow transplantation induce severe thymic injury, we also are exploring new approaches to protect the thymic epithelial cells (TEC) against injury including the use of cytokines that stimulate TEC proliferation/repair, agents that protect against genotoxic stress, and those that repair stromal cell injury in the thymus and periphery. The mechanism(s) responsible for the protective effects of these biological agents are being explored in wild-type and in transgenic mice with disruptions of various signaling pathways. Within TECs, we are examining the thymocyte signals that regulate TEC function and characterizing the effects of micro-RNA regulation on TEC regeneration and function. In complimentary studies, we are developing strategies to induce pluriopotent progenitor cells to differentiate into TECs, which will be used as a cellular therapy to replace damaged TEC. We also are analyzing the mature T cell response to foreign antigens in transplanted mice to better understand the qualitative defects associated with post-transplant T cell reconstitution and applying those to novel strategies to repair injury stromal cells in peripheral lymphoid organs.
4. Graft-versus-leukemia (GVL). Projects are ongoing to identify the host mechanisms responsible for tumor-mediated immune suppression of endogenous T effector cells, focusing on negative regulators of immune response expressed on the cell surface or via intracellular pathways. Adoptive T cell immunotherapy is being tested using new approaches to generate T effector cells that have superior in vivo cytolytic potential and/or result in increased persistence of transferred T cells. T cell immune therapy is used in combination with approaches that dampen the host immune suppressive response , cause homeostatic expansion of T cells via the induction of lymphopenia, target tumor cells or support T cell recruitment and survival within secondary lymphoid organs.
5. Gene therapy/repair. As an alternative to transplantation, we are using molecular strategies to correct congenital disorders. To treat immune deficiency disorders, studies are being performed to achieve homologous recombination or site-directed integration for gene replacement using zinc finger nucleases or TALENS in hematopoietic stem cells. Recipients are analyzed for molecular and phenotypic correction.
- 1975 BS-Cum Laude, Albany Medical College Research Award
- 1981-1983 American Cancer Society Clinical Fellowship Award
- 1982-1984 NIH-NCI National Research Service Award
- 1985-1987 Leukemia Society of America Fellowship Award
- 1985-1990 National Institutes of Health-National Institute Clinical Investigator Award
- 1992-1995 Edward Mallinckrodt Foundation Scholar Award
- 1992-1996 Vice-Chair New Agents, BMT, Childrens Cancer Group
- 1996 Elected to the American Society of Clinical Investigation
- 1999-present Andersen Chair in Transplantation Immunology
- 1998-present MERIT Award, National Heart Lung Blood Institute
- 2002 Elected to the Association of American Physicians
- 2005 E. Donnell Thomas Lecture
- NIH symposium on Translational Immunology as related to Cancer, Co-Chair Transplantation and anti-tumor therapies, 2005
- NIH Expert Panel Member, Transplantation Research, 2005
- Co-Chair, NHLBI Panel Strategic Planning for Cellular Therapies, 2005-present