The aim of this core is to use a xenotransplantation murine model to provide in vivo readouts for experiments proposed in this program project. Specifically, this model will be used for the following purposes: 1. To optimize proliferation and function of T regulatory cells (Treg) for suppression of alloreactive responses. 2. To perform studies testing the hypothesis that human thymocyte progenitor cells (Tprog) will accelerate human thymopoiesis and peripheral blood T cell responses in immunodeficient mice. 3. To optimize proliferation and function of natural killer (NK) cells for leukemia therapy. These data will in turn inform the design of future clinical trials. The core leader will provide valuable knowledge of the stem cell biology, gene manipulations, murine models, and clinical hematopoietic cell transplantation, all relevant to this application. Core D is unique in its capability to allow two of the three Principal Investigators (who do not have access to preclinical murine models;Project 1 and 3) with a critical shared resource to enhance their scientific program.

Public Health Relevance

Our overall goal is to enhance beneficial effects of cord blood transplantation using subpopulations of immune cells for enhanced lympho-hematopoietic recovery in humanized mice. Investigators in Core D will receive T regulatory, T progenitor and NK cells from investigators in Project 1, 2, and 3, respectively, and evaluate them in immunodeficient mice. These in vivo readouts of cord blood hematopoietic stem cells and additional subsets of human cells will then inform the design of clinical trials.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
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Special Emphasis Panel (ZCA1-RPRB-J)
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University of Minnesota Twin Cities
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Romee, Rizwan; Cooley, Sarah; Berrien-Elliott, Melissa M et al. (2018) First-in-human phase 1 clinical study of the IL-15 superagonist complex ALT-803 to treat relapse after transplantation. Blood 131:2515-2527
Stefanski, Heather E; Jonart, Leslie; Goren, Emily et al. (2018) A novel approach to improve immune effector responses post transplant by restoration of CCL21 expression. PLoS One 13:e0193461
Owen, David L; Mahmud, Shawn A; Vang, Kieng B et al. (2018) Identification of Cellular Sources of IL-2 Needed for Regulatory T Cell Development and Homeostasis. J Immunol 200:3926-3933
Osborn, Mark J; Lees, Christopher J; McElroy, Amber N et al. (2018) CRISPR/Cas9-Based Cellular Engineering for Targeted Gene Overexpression. Int J Mol Sci 19:
Oh, Felix; Todhunter, Deborah; Taras, Elizabeth et al. (2018) Targeting EGFR and uPAR on human rhabdomyosarcoma, osteosarcoma, and ovarian adenocarcinoma with a bispecific ligand-directed toxin. Clin Pharmacol 10:113-121
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
Xing, Yan; Smith, Michelle J; Goetz, Christine A et al. (2018) Thymic Epithelial Cell Support of Thymopoiesis Does Not Require Klotho. J Immunol 201:3320-3328
Prestipino, Alessandro; Emhardt, Alica J; Aumann, Konrad et al. (2018) Oncogenic JAK2V617F causes PD-L1 expression, mediating immune escape in myeloproliferative neoplasms. Sci Transl Med 10:

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