Cellular and Molecular Studies of Bone Marrow Transplant

骨髓移植的细胞和分子研究

• 批准号: 7927647
• 负责人: JAMES L. M. FERRARA
• 金额: $ 60万
• 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 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7927647
• 关键词: Allogeneic Bone Marrow Transplantation; Allogenic; Apoptosis; Area; Biostatistics Core; Bone Marrow Transplantation; Cancer Patient; Clinical; Clinical Trials; Collaborations; Engineering; Excision; Genomics; Goals; Hematologic Neoplasms; Immune response; Lead; Molecular; Patients; Phase; Program Research Project Grants; Proteomics; Regulation; Skin; T-Lymphocyte; Tissues; Translational Research; cytokine; graft vs host disease; insight; keratinocyte; leukemia; mortality; novel; novel therapeutics; premature; prevent

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）：该计划项目赠款（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，并作为血液学性恶性肿瘤患者的新型治疗策略的转化研究平台。同种异体BMT后，移植物与宿主疾病（GVHD）仍然是病态和死亡率的主要原因，并防止了这种治疗性疗法在癌症患者中的应用。因此，BMT整个领域的长期目标是制定新的策略，将有益的移植物与白血病（GVL）效应GVL与GVHD分开。该PPG通过：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械洞察来充当转化研究平台。因此，这些研究的意义在为癌症患者（尤其是血液学恶性肿瘤的患者）带来新疗法的潜力方面的潜力。该PPG的主要主题是调节对同种异体宿主组织的供体免疫反应，而无需从供体移植物中去除T细胞。 GVHD中细胞因子失调的主题以几种方式发展，并统一了整个PPG的项目负责人之间的合作和互动，并为协同作用提供了多种机会。 PPG由三个项目和两个核心组成： 调节GVHD中早产角质形成细胞凋亡的调节 临床异种BMT中的细胞因子调节策略 核心管理和生物统计学 核心皮肤分析和表皮工程 核心C蛋白质组学和基因组分析