This Program Project Grant (PPG) seeks continued support for basic and translational clinical studies in the setting of hematopoietic cell transplantation (HCT). These studies serve as a paradigm for cellular therapeutics and the exploration of immune function for the treatment of cancer. The PPG is composed of five interactive Projects and four Cores focused on the themes of graft vs host disease biology and prevention, disease relapse treatment and prevention and immune reconstitution. The Program utilizes innovative animal modeling, imaging, molecular biological assessment of immunoglobulin and T cell receptor sequencing and novel clinical trial interventional studies with highly purified cell populations to explore the fundamental aspects of transplantation biology and improve outcomes for patients undergoing both autologous and allogeneic HCT. The Projects focus on different aspects of immune effector (conventional and memory CD4+ and CD8+ T cells, cytokine induced killer cells) and regulatory (Treg, NK-T) cell biology, vaccination strategies (CpG stimulated cancer cells), common lymphoid progenitor cell biology and immune recovery in a highly interactive and complementary fashion. In each of the Projects both fundamental biological explorations in animal models and clinical translation in phase 1/11 trials are proposed aimed at enhancing the clinical efficacy of HCT. The Projects and Project leaders are highly interactive using similar animal models, imaging strategies, novel approaches to analysis of T cell receptor sequencing to analyze distinct yet iterative approaches to answer fundamental biological questions and explore translation to the clinic. The four Cores provide administrative, clinical trial, molecular, sample distribution and cellular manufacture support. Ou hypothesis is that through the study of the cellular components of hematopoietic and immunological progenitor, regulatory and effector cells will result in novel insights into improvin immune function resulting in more effective therapy for patients with serious hematological malignancies.
This PPG focuses on the immune basis of hematopoietic cell transplantation and the treatment of patients with severe hematological malignancies. The fundamental and clinical insights gained also have major implications for induction of tolerance in solid organ transplantation and for the treatment of patients with autoimmune disorders.
|Sen, Nandini; Arvin, Ann M (2016) Dissecting the Molecular Mechanisms of the Tropism of Varicella-Zoster Virus for Human T Cells. J Virol 90:3284-7|
|Pierini, Antonio; Alvarez, Maite; Negrin, Robert S (2016) NK Cell and CD4+FoxP3+ Regulatory T Cell Based Therapies for Hematopoietic Stem Cell Engraftment. Stem Cells Int 2016:9025835|
|Khodadoust, M S; Luo, B; Medeiros, B C et al. (2016) Clinical activity of ponatinib in a patient with FGFR1-rearranged mixed-phenotype acute leukemia. Leukemia 30:947-50|
|Xu, Lian; Hunter, Zachary R; Tsakmaklis, Nicholas et al. (2016) Clonal architecture of CXCR4 WHIM-like mutations in WaldenstrÃ¶m Macroglobulinaemia. Br J Haematol 172:735-44|
|Pierini, Antonio; Strober, William; Moffett, Caitlin et al. (2016) TNF-Î± priming enhances CD4+FoxP3+ regulatory T-cell suppressive function in murine GVHD prevention and treatment. Blood 128:866-71|
|Nakasone, Hideki; Sahaf, Bita; Tian, Lu et al. (2016) Presensitization to HY antigens in female donors prior to transplant is not associated with male recipient post-transplant HY antibody development nor with clinical outcomes. Haematologica 101:e30-3|
|Pierini, Antonio; Colonna, Lucrezia; Alvarez, Maite et al. (2015) Donor Requirements for Regulatory T Cell Suppression of Murine Graft-versus-Host Disease. J Immunol 195:347-55|
|Ohgami, Robert S; Ma, Lisa; Merker, Jason D et al. (2015) Next-generation sequencing of acute myeloid leukemia identifies the significance of TP53, U2AF1, ASXL1, and TET2 mutations. Mod Pathol 28:706-14|
|Nakasone, Hideki; Remberger, Mats; Tian, Lu et al. (2015) Risks and benefits of sex-mismatched hematopoietic cell transplantation differ according to conditioning strategy. Haematologica 100:1477-85|
|Kelley, Todd W; Arber, Daniel A; Gibson, Christine et al. (2015) Template for Reporting Results of Monitoring Tests for Patients With Chronic Myelogenous Leukemia (BCR-ABL1(+)). Arch Pathol Lab Med :|
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