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Growth Regulatory Pathways in Vascular Anomalies

血管异常的生长调节途径

基本信息

批准号：
8685129
负责人：
THUY L. PHUNG
金额：
$ 7.67万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-07-01 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8685129
关键词：
Adverse effects Affect Alternative Therapies Applications Grants Area Automobile Driving Binding Proteins Biological Biological Models Biology Blood Vessels Cells Chemicals Child Complex Critical Pathways Cytoskeletal Modeling Data Development Diabetes Mellitus Disease Family Funding Gene Expression Genes Goals Grant Growth Growth Factor Growth and Development function Hemangioma In Vitro Laboratory Research Laser Surgery Malignant Neoplasms Mediating Mediator of activation protein Mission Molecular Molecular Profiling National Institute of Arthritis and Musculoskeletal and Skin Diseases Outcome Pathogenesis Pathway interactions Patients Principal Investigator Protein Isoforms Regulation Regulatory Pathway Research Research Personnel Retinoblastoma Retinoblastoma Genes Role Sclerotherapy Signal Pathway Signal Transduction Steroids Strawberry nevus Tissues Vascular Endothelial Growth Factor Receptor Work angiogenesis base cell growth congenital anomaly effective therapy functional disability histone modification in vivo in vivo Model inhibitor/antagonist interest member mouse model novel novel therapeutics professor programs therapeutic target

项目摘要

DESCRIPTION (provided by applicant): Vascular anomalies are congenital dysregulation of vascular development and growth, and consist of a wide spectrum of disorders, including infantile hemangioma. Although infantile hemangioma is common and can cause severe physical and functional impairment for the child, the pathogenesis of this disease is poorly understood. Several angiogenic regulators of hemangioma have been identified. However, little is known regarding the signaling mechanisms that regulate hemangioma development by these factors. Hemangioma cells have high levels of activated Akt, a key regulator of vascular growth. There are 3 known Akt isoforms, and the diverse biological outcomes of Akt signaling may be due in part to the different functions of these isoforms. Our long-term goal is to understand the molecular mechanism of growth factor signaling pathways in the regulation of vascular development and growth. The objective of this proposal is to unravel the biological roles of Akt isoforms in hemangioma development. Our Specific Aims are: (1) to investigate the opposing functions of Akt1 and Akt3 in hemangioma, and (2) to determine the role of retinoblastoma binding protein 4 in mediating the function of Akt3. This work will contribute to our fundamental understanding of key signaling pathways in angiogenesis, and open new therapeutic options for children with complex hemangiomas by targeting critical pathways driving hemangioma growth.

描述（由申请人提供）：血管异常是血管发育和生长的先天性失调，由多种疾病组成，包括婴儿血管瘤。尽管婴儿血管瘤很常见，并且可能导致儿童严重的身体和功能损伤，但对该疾病的发病机制知之甚少。已鉴定出几种血管瘤的血管生成调节因子。然而，人们对这些因素调节血管瘤发展的信号机制知之甚少。血管瘤细胞具有高水平的活化 Akt，它是血管生长的关键调节因子。有 3 种已知的 Akt 同工型，Akt 信号转导的不同生物学结果可能部分归因于这些同工型的不同功能。我们的长期目标是了解生长因子信号通路调节血管发育和生长的分子机制。该提案的目的是阐明 Akt 同工型在血管瘤发展中的生物学作用。我们的具体目标是：(1) 研究 Akt1 和 Akt3 在血管瘤中的相反功能，(2) 确定视网膜母细胞瘤结合蛋白 4 在介导 Akt3 功能中的作用。这项工作将有助于我们对血管生成中关键信号通路的基本理解，并通过针对驱动血管瘤生长的关键通路，为患有复杂血管瘤的儿童开辟新的治疗选择。