Cellular and Molecular Studies of Bone Marrow Transplant

描述（由申请人提供）：该计划项目资助（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，并作为恶性血液病患者新治疗策略的转化研究平台。移植物抗宿主病（GVHD）仍然是同种异体BMT后发病率和死亡率的主要原因，并且阻止这种治愈性疗法在癌症患者中的更广泛应用;因此，整个BMT领域的长期目标是开发新的策略以将有益的移植物抗白血病（GVL）效应GVL与GVHD分开。该PPG通过以下方式实现这一目标：1）探索GVHD的细胞和分子机制; 2）通过在BMT患者的I/II期临床试验中应用这些机制见解，作为转化研究平台发挥作用。因此，这些研究的意义在于它们可能为癌症患者，特别是血液系统恶性肿瘤患者带来新的治疗方法。该PPG的主要主题是调节供体对同种异体宿主组织的免疫应答，而不从供体移植物中去除T细胞。GVHD中细胞因子失调的主题以多种方式发展，并统一了整个PPG，增加了项目负责人之间的合作和互动，并提供了多种协同作用的机会。该项目由三个项目和两个核心组成： 移植物抗宿主病中角质形成细胞凋亡的调控 临床异基因骨髓移植中的细胞因子调控策略 芯A 给药和生物统计学 核心B 皮肤分析和表皮工程 芯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