The scientific goals of the Transplant Biology and Therapy (TBT) Program are to enhance the efficacy of hematopoietic cell transplantation (HCT) and related cellular therapies through augmented anti-neoplastic activity, improve the safety of HCT by limiting graft-versus-host disease (GVHD) and enhancing immune reconstitution through accelerated engraftment and immune progenitor recovery, and export University of Minnesota discoveries to a national or multicenter platform for definitive testing. To achieve these goals, the Program will focus on the following Aims: 1) to develop new cellular therapeutics to prevent relapse after transplantation, including natural killer (NK) cell activation and the adoptive transfer of engineered T and NK cells; 2) to establish methods for reducing transplant-related morbidity and mortality, including hematopoietic stem cell expansion to accelerate engraftment, novel strategies to limit the risk of GVHD, and cell-based interventions to augment immune reconstitution and limit the hazards of opportunistic infection; and 3) to bring promising transplantation advances devised at the University of Minnesota to national clinical trials for definitive evaluation. The TBT Program is led by experienced co-leaders, MDs John Wagner and Daniel Weisdorf and has 39 members, representing 7 departments and 4 schools or colleges (Medical School, College of Pharmacy, School of Public Health, College of Science and Engineering). For the last budget year, research members were supported by $1.9 million in direct costs from the National Cancer Institute and $5.0 million in direct costs from all peer-reviewed sources. Since 2013, Program members have published 865 papers (16% in high-impact journals), 34% of which resulted from intraprogrammatic collaborations, 25% from interprogrammatic collaborations, and 84% from external collaborations. Since 2013, 194 clinical trials in all clinical research categories have opened under this programmatic area and have enrolled 4083 participants. Leukemia is the leading cause of death for Minnesota's children and Minnesota has a higher incidence of MDS/AML than the national average. Our translational research targeting hematologic malignancies and GVHD directly addresses these unique cancer burdens of our catchment area. Since 2013, with Masonic Cancer Center support, we have recruited 3 new investigators: Frank Cichocki, PhD; Shernan Holtan, MD; and Armin Rashidi MD, PhD. Each has differing skills and research emphasis and will enhance the goals of the TBT Program. Additionally, the Masonic Cancer Center has invested $250,000 in 9 pilot projects awarded to members of the Program. The scientific advances made in this program form the basis for our first Scientific Priority for Growth ? expand recent discoveries in immunotherapy and cellular therapies to include solid tumors (SPG1). While the focus of TBT program has been on hematologic malignancies, the principles, technologies, and approaches are now being translated into solid tumors.

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National Cancer Institute (NCI)
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Subcommittee I - Transistion to Independence (NCI)
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University of Minnesota Twin Cities
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Lin, Lifeng; Chu, Haitao; Murad, Mohammad Hassan et al. (2018) Empirical Comparison of Publication Bias Tests in Meta-Analysis. J Gen Intern Med 33:1260-1267
Rashidi, Armin; Ebadi, Maryam; Said, Bassil et al. (2018) Absence of early HHV-6 reactivation after cord blood allograft predicts powerful graft-versus-tumor effect. Am J Hematol :
Bejanyan, Nelli; Brunstein, Claudio G; Cao, Qing et al. (2018) Delayed immune reconstitution after allogeneic transplantation increases the risks of mortality and chronic GVHD. Blood Adv 2:909-922
Bachanova, Veronika; Sarhan, Dhifaf; DeFor, Todd E et al. (2018) Haploidentical natural killer cells induce remissions in non-Hodgkin lymphoma patients with low levels of immune-suppressor cells. Cancer Immunol Immunother 67:483-494
Hupp, Meghan; Williams, Sarah; Dunnette, Brian et al. (2018) Comparison of evaluation techniques, including digital image analysis, for MYC protein expression by immunohistochemical stain in aggressive B-cell lymphomas. Hum Pathol :
Rashidi, Armin; Shanley, Ryan; Holtan, Shernan G et al. (2018) Pretransplant Serum Citrulline Predicts Acute Graft-versus-Host Disease. Biol Blood Marrow Transplant 24:2190-2196
Ma, Bin; Zarth, Adam T; Carlson, Erik S et al. (2018) Methyl DNA Phosphate Adduct Formation in Rats Treated Chronically with 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone and Enantiomers of Its Metabolite 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol. Chem Res Toxicol 31:48-57
Hatsukami, Dorothy K; Luo, Xianghua; Jensen, Joni A et al. (2018) Effect of Immediate vs Gradual Reduction in Nicotine Content of Cigarettes on Biomarkers of Smoke Exposure: A Randomized Clinical Trial. JAMA 320:880-891
Lee, Hak Rae; Leslie, Faith; Azarin, Samira M (2018) A facile in vitro platform to study cancer cell dormancy under hypoxic microenvironments using CoCl2. J Biol Eng 12:12
Yang, Libang; Herrera, Jeremy; Gilbertsen, Adam et al. (2018) IL-8 mediates idiopathic pulmonary fibrosis mesenchymal progenitor cell fibrogenicity. Am J Physiol Lung Cell Mol Physiol 314:L127-L136

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