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Semaphorin 3F: Structure, Function, and Anti-Metastatic Activity

Semaphorin 3F：结构、功能和抗转移活性

基本信息

批准号：
7936357
负责人：
DIANE Renee BIELENBERG
金额：
$ 15.93万
依托单位：
BOSTON CHILDREN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-07-01 至 2011-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7936357
关键词：
Animal Model Area Benign Biochemistry Biological Testing Biology Blood Vessels Cancer Patient Collaborations Cutaneous Disease Encapsulated Engineering Enzymes Goals Howard Temin Award Human Infiltration Interferon-beta Interferons Lymphangiogenesis Lymphatic vessel Malignant Neoplasms Malignant neoplasm of lung Mentored Research Scientist Development Award Mentors Molecular Neoplasm Metastasis Neuropilins Pathologic Neovascularization Patients Pediatric Hospitals Phenotype Physiologic Neovascularization Physiological Predisposition Process Protein Engineering Proteins Research Research Personnel Research Project Grants Research Proposals Role Sampling Site Stable Disease Strawberry nevus Structure Testing Training Tumor Angiogenesis Tumor Cell Line Tumor Suppressor Genes Vascular Endothelial Growth Factor Receptor angiogenesis antiangiogenesis therapy career fighting follow-up human SEMA3F protein instructor lymph nodes medical schools meetings neoplastic cell neovascularization novel novel therapeutics programs protein purification surgical research therapeutic angiogenesis tool tumor

项目摘要

DESCRIPTION (provided by applicant): The candidate, Dr. Diane Bielenberg, is an instructor in the Surgical Research Division at Children's Hospital and Harvard Medical School, chaired by Dr. Judah Folkman, the pioneer of the field of angiogenesis research. As part of the Vascular Biology Program, Dr. Bielenberg, a cancer biologist, has specialized in studies of metastasis, the spread of malignant tumor cells from one site in the body to another. The longterm career goals of the applicant are to remain in academic research and continue to study the biology of cancer metastasis and angiogenesis. Most cancer patients die from metastasis, and only by understanding the biology of this process can we hope to develop better tools to fight this disease. Dr. Bielenberg has previously studied the molecular mechanisms involved in anti-angiogenesis therapy by interferons, the role of endogenous interferon-beta in the involution of cutaneous infantile hemangiomas, and the identification and anti-tumor activity of a natural soluble receptor for vascular endothelial growth factor called soluble neuropilin. Since being promoted to an instructor, Dr. Bielenberg has focused on a novel suppressor of metastasis, called Semaphorin 3F. Semaphorin 3F is commonly deleted in lung cancer and is a putative tumor suppressor gene, but recently Dr. Bielenberg and her mentor, Dr. Michael Klagsbrun, have shown that Semaphorin 3F is inversely correlated with metastasis in many tumor cell lines. When Semaphorin 3F was expressed in metastatic cells, the tumors remarkably reverted to a benign, hypo-vascular and encapsulated tumor phenotype. This K01 research proposal will follow-up this exciting finding and focus on the molecular mechanisms responsible for the anti-metastatic effect of Semaphorin 3F. We hypothesize that Semaphorin 3F will regulate key steps in the metastatic cascade including angiogenesis and lymphangiogenesis and may offer a novel therapeutic strategy for patients with metastatic disease. A K01 award would facilitate the transition of this candidate from instructor to an independent investigator in the Department of Surgical Research at Harvard Medical School by providing additional training in areas of biochemistry including protein engineering and protein purification, as well as enabling additional collaborations and participation in regional and national meetings. Most of all, a Howard Temin Award would enable the continuation of this research project toward the ultimate goal of long-term stable disease.

描述(申请人提供)：应聘者Diane Bielenberg博士是儿童医院和哈佛医学院外科研究部的讲师，由血管生成研究领域的先驱Judah Folkman博士担任主席。作为血管生物学项目的一部分，癌症生物学家比伦伯格博士专门研究转移，即恶性肿瘤细胞从体内一个部位扩散到另一个部位。申请者的长期职业目标是继续从事学术研究，继续研究癌症转移和血管生成的生物学。大多数癌症患者死于转移，只有了解这一过程的生物学原理，我们才有希望开发出更好的工具来对抗这种疾病。Bielenberg博士之前曾研究过干扰素抗血管生成治疗的分子机制，内源性干扰素-β在皮肤婴儿血管瘤消退中的作用，以及一种天然的可溶性血管内皮生长因子受体--可溶性神经纤毛素的鉴定和抗肿瘤活性。自从被提升为讲师以来，比伦伯格博士一直专注于一种名为Semaphorin 3F的新型转移抑制因子。信号素3F在肺癌中通常是缺失的，是一种可能的肿瘤抑制基因，但最近比伦伯格博士和她的导师迈克尔·克拉格斯布伦博士发现，在许多肿瘤细胞系中，信号素3F与转移呈负相关。当Semaphorin 3F在转移细胞中表达时，肿瘤明显恢复为良性、少血管和包膜的肿瘤表型。这项K01研究计划将跟进这一令人兴奋的发现，并将重点放在Semaphorin 3F抗转移作用的分子机制上。我们推测，Semaphorin 3F将调节转移级联反应中的关键步骤，包括血管生成和淋巴管生成，并可能为转移性疾病患者提供一种新的治疗策略。K01奖项将通过提供包括蛋白质工程和蛋白质纯化在内的生物化学领域的额外培训，以及促进更多的合作和参与地区和国家会议，促进这位候选人从哈佛医学院外科研究部的讲师转变为独立研究员。最重要的是，霍华德·特明奖将使这项研究项目能够继续朝着长期稳定的疾病的最终目标前进。