Cellular and Molecular Studies of Bone Marrow Transplant

描述(由申请人提供)：该计划项目拨款(PPG)的总体目标是探索异基因骨髓移植(BMT)的细胞和分子机制，并为恶性血液病患者的新治疗策略提供一个翻译研究平台。移植物抗宿主病(GVHD)仍然是异基因骨髓移植后发病率和死亡率的主要原因，阻碍了这种根治疗法在癌症患者中的广泛应用；因此，整个BMT领域的一个长期目标是开发新的策略，将有益的移植物抗白血病(GVL)效应GVL从GVHD中分离出来。PPG通过以下方式为这一目标做出贡献：1)探索GVHD的细胞和分子机制；2)在骨髓移植患者的I/II期临床试验中应用这些机制见解，作为翻译研究平台发挥作用。因此，这些研究的意义在于它们有可能为癌症患者带来新的治疗方法，特别是那些患有血液系统恶性肿瘤的患者。这个PPG的主要主题是在不从供体移植物中移除T细胞的情况下调节供体对同种异体宿主组织的免疫反应。GVHD中细胞因子失调这一主题以几种方式发展，并统一了整个PPG，增加了项目负责人之间的合作和互动，并提供了多重协同机会。PPG由三个项目和两个核心组成： 移植物抗宿主病早期角质形成细胞凋亡的调控 细胞因子调控策略在临床骨髓移植中的应用 核心A管理和生物统计学 核心B皮肤分析和表皮工程 核心C蛋白质组和基因组分析

DESCRIPTION (provided by applicant): The overall goal of this program project grant (PPG) is to explore the cellular and molecular mechanisms of allogeneic bone marrow transplantation (BMT) and to serve as a translational research platform for novel therapeutic strategies for patients with hematologic malignancies. Graft versus host disease (GVHD) remains a major cause of morbility and mortality after allogeneic BMT and prevents this curative therapy from wider application in cancer patients; thus a long term goal for the entire area of BMT is to develop new strategies to separate a beneficial graft versus leukemia (GVL) effect GVL from GVHD. This PPG contributes to that goal by: 1) exploring the cellular and molecular mechanisms of GVHD; and 2) functioning as a translational research platform by applying these mechanistic insights in Phase I/II clinical trials in BMT patients. The significance o f these studies therefore Iies in their potential to lead to novel therapies for cancer patients, particularly those with hematologic malignancies. The major theme of this PPG is the modulation of donor immune responses to allogeneic host tissues without removal of T cells from the donor graft. This theme of cytokine dysregulation in GVHD develops in several ways and unifies the entire PPG increasing collaborations and interactions among project leaders and provides multiple opportunities for synergy. The PPG consists of three projects and two cores: Regulation of Premature Keratinocyte Apoptosis in GVHD Cytokine Modulation Strategies in Clinical AIIogeneic BMT Core A Administration and Biostatistics Core B Skin Analysis and Epidermal Engineering Core C Proteomic and Genomic Analyses