Bruce Blazar
,
Credentials
MD

Regents Professor, Children's Cancer Research Fund Land Grant Chair in Pediatric Oncology, Department of Pediatrics
Faculty Member, Division of Pediatric Blood and Marrow Transplantation & Cellular Therapy
Vice Dean for Clinical Investigation, Medical School
Associate Vice President for Clinical and Translational Science, Academic Health Center
Director, Clinical and Translational Science Institute (CTSI)
Director, Center for Translational Medicine
Faculty Member, Microbiology, Immunology and Cancer Biology (MICaB) Ph.D. Graduate Program
Preceptor, Medical Scientist Training Program (Combined MD/PhD Training Program)
Biography

Bio

Dr. Blazar is a Regents Professor of Pediatrics in the Division of Blood and Marrow Transplant & Cellular Therapy and attends on the Pediatric Blood and Marrow Transplantation (BMT) service. Dr. Blazar is the recipient of the Children’s Cancer Research Fund Land Grant Chair in Pediatric Oncology to recognize his pioneering work in the development of novel immune-based therapies. He is the Founding Director of the Clinical and Translational Sciences Institute and the Founding Director of the Center for Translational Medicine.
Dr. Blazar received his MD 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 is the recipient of National Institutes of Health (NIH) MERIT Awards from the National Heart, Lung, and Blood Institute as well as the National Institute of Allergy and Infectious Diseases. He is the Principal Investigator of the UMN Clinical and Translational Sciences Award (U54), NIH funded R01 grants, P01 Projects, a U19 grant subcontract and Leukemia and Lymphoma Translational Research grants focusing on BMT immunological studies. Dr. Blazar is the author of more than 725 manuscripts, which have appeared in premier peer-reviewed publications.

Research Summary

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 that regulate these responses at the level of the GVHD target organ. We are examining cell-based therapies such as regulatory T cells (see below) in mice and in patients and myeloid-derived suppressor cells (see below). 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. We have tested drugs and cell populations that affect this interaction, many of which have been brought into the clinic, one of which has received FDA approval. For approaches that reduce acute or chronic GVHD in mice, we are assessing their immune competency to malignant cells (to assess graft-versus-leukemia, GVL) and to pathogens.
2. Regulatory cells. A) regulatory T cells (Treg) . Using phosphoproteomics, metabolomics, micro-RNA/mRNA binding partners and flow cytometry, we have identified pathways that can be targeted to upregulate Treg potency in mice and humans. Proof-of-principle has been demonstrated in allogeneic and xenogeneic mouse models . Other studies are focused on genome engineering approaches that should optimize GVHD and autoimmune disease treatment. Knockout, transgenic and conditional inducible strains of mice are utilized along with 2-photon microscopy to identify mechanisms of in vivo suppression. B) Myeloid-derived suppressor cells (MDSC). We have developed techniques to differentiation and active MDSCs from normal hematopoietic sources in mice and humans. Our studies have shown in murine allogeneic GVHD systems that inflammasome activation converts MDSCs into immune stimulatory cells. Knockout of inflammasome components or inflammasome inducers have ameliorated this loss of function. Ongoing studies are examining the production of human MDSCs from inducible pluriopotent stem cells, with or without genome engineering approaches, for mechanistic purposes and potential future clinical trials.
3. T cell generation from induced pluripotent stem cells (IPSCs). In order to understand the optimal requirements for T cell anti-cancer or anti-pathogen responses, we have focused on reprogramming various human cell populations into thymic progenitor cells and mature T cells. Transcriptomics and epigenetics are investigated. Genome modification of IPSCs readily induces chimeric antigen receptor (CAR) expression that directs T cells to lymphoma cells. Using a model that incorporates a CAR used in the clinic for treating B cell malignancies and a transgenic strain that expresses human B cell antigens, cytokine release syndrome and neurotoxicity have been shown. Studies are being examined to explore different approaches to mitigate these side-effects.

Clinical Summary

Pediatric hematology/oncology
Bone marrow transplant
Graft-versus-host disease
Graft-versus-leukemia
Tumor immunotherapy

Education

MD, Albany Medical College, Albany, NY

Fellowships, Residencies, and Visiting Engagements

Fellowship in Hematology/Oncology and Bone Marrow Transplantation,
University of Minnesota Medical School
Minneapolis, Minnesota, United States
Postdoctoral Research Associate in Pediatrics,
University of Minnesota
Minneapolis, Minnesota, United States
Residency in Pediatrics,
University of Minnesota Medical School
Minneapolis, Minnesota, United States

Licensures and Certifications

Pediatric Hematology/Oncology, American Board of Pediatrics
Pediatrics, American Board of Pediatrics

Honors and Recognition

Children's Cancer Research Fund (CCRF) Land Grant Chair in Pediatric Oncology
Pediatric Blood and Marrow Transplant Consortium, Lifetime Achievement Award and Lecture
Richard O’Reilly Stem Cell Transplant Lectureship, Memorial Sloan Kettering Cancer Institute
25th Annual Mark E. Nesbit Lectureship in Pediatric Oncology, University of Minnesota
Innovator in Basic Science Award, Department of Pediatrics, University of Minnesota
4th annual University of Minnesota Dean’s Distinguished Research Lectureship
Keystone Symposium: Co-organizer, Chair and Speaker, Symposium on Cell Therapy
Richard Schiff Lectureship, Clinical Immunology Society
E Donnall Thomas Lecture and Prize, American Society of Hematology
Minneapolis-St. Paul 2022 Top Doctor, Minneapolis-St. Paul Magazine