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.
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.
| de Witte, Moniek A; Sarhan, Dhifaf; Davis, Zachary et al. (2018) Early Reconstitution of NK and ?? T Cells and Its Implication for the Design of Post-Transplant Immunotherapy. Biol Blood Marrow Transplant 24:1152-1162 |
| Zeiser, Robert; Blazar, Bruce R (2018) Acute Graft-versus-Host Disease. N Engl J Med 378:586 |
| Blazar, Bruce R; MacDonald, Kelli P A; Hill, Geoffrey R (2018) Immune regulatory cell infusion for graft-versus-host disease prevention and therapy. Blood 131:2651-2660 |
| Rothenberger, Meghan; Wagner, John E; Haase, Ashley et al. (2018) Transplantation of CCR5?32 Homozygous Umbilical Cord Blood in a Child With Acute Lymphoblastic Leukemia and Perinatally Acquired HIV Infection. Open Forum Infect Dis 5:ofy090 |
| Lu, Yunjie; Gao, Ji; Zhang, Shaopeng et al. (2018) miR-142-3p regulates autophagy by targeting ATG16L1 in thymic-derived regulatory T cell (tTreg). Cell Death Dis 9:290 |
| Cichocki, Frank; Wu, Cheng-Ying; Zhang, Bin et al. (2018) ARID5B regulates metabolic programming in human adaptive NK cells. J Exp Med 215:2379-2395 |
| Taraseviciute, Agne; Tkachev, Victor; Ponce, Rafael et al. (2018) Chimeric Antigen Receptor T Cell-Mediated Neurotoxicity in Nonhuman Primates. Cancer Discov 8:750-763 |
| Felices, Martin; Lenvik, Alexander J; McElmurry, Ron et al. (2018) Continuous treatment with IL-15 exhausts human NK cells via a metabolic defect. JCI Insight 3: |
| Sarhan, Dhifaf; Hippen, Keli L; Lemire, Amanda et al. (2018) Adaptive NK Cells Resist Regulatory T-cell Suppression Driven by IL37. Cancer Immunol Res 6:766-775 |
| Williams, Robin L; Cooley, Sarah; Bachanova, Veronika et al. (2018) Recipient T Cell Exhaustion and Successful Adoptive Transfer of Haploidentical Natural Killer Cells. Biol Blood Marrow Transplant 24:618-622 |
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