Cellular and Molecular Studies of Bone Marrow Transplant

骨髓移植的细胞和分子研究

• 批准号: 6826222
• 负责人: JAMES L. M. FERRARA
• 金额: $ 148.12万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-24 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6826222
• 关键词: bone marrow transplantation; clinical research; graft versus host disease; transplantation immunology

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

描述（由申请人提供）：该计划项目资助（PPG）的总体目标是探索同种异体骨髓移植（BMT）的细胞和分子机制，并作为血液病患者新治疗策略的转化研究平台恶性肿瘤。移植物抗宿主病 (GVHD) 仍然是同种异体 BMT 后发病和死亡的主要原因，并阻碍了这种治疗方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策略，将有益的移植物抗白血病 (GVL) 效应 GVL 与 GVHD 区分开来。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) 通过将这些机制见解应用于 BMT 患者的 I/II 期临床试验，发挥转化研究平台的作用。因此，这些研究的意义在于它们有可能为癌症患者，特别是患有血液系统恶性肿瘤的患者带来新的疗法。该 PPG 的主题是在不去除供体移植物中 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 中细胞因子失调的主题以多种方式发展，并将整个 PPG 统一起来，增加项目领导者之间的合作和互动，并提供多种协同机会。 PPG由三个项目和两个核心组成： GVHD 中过早角质形成细胞凋亡的调节 临床异基因 BMT 中的细胞因子调节策略 核心 A 管理和生物统计学 核心 B 皮肤分析和表皮工程 Core C 蛋白质组和基因组分析