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

Semaphorin 3F：结构、功能和抗转移活性

• 批准号: 7640865
• 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
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7640865
• 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

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（由申请人提供）：候选人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Bielenberg博士专门研究转移，即恶性肿瘤细胞从体内的一个部位扩散到另一个部位。申请人的长期职业目标是继续从事学术研究，并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，我们才有希望开发出更好的工具来对抗这种疾病。Bielenberg博士以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在皮肤婴儿血管瘤退化中的作用，以及血管内皮生长因子天然可溶性受体（称为可溶性神经纤毛蛋白）的鉴定和抗肿瘤活性。自从晋升为讲师以来，Bielenberg博士一直专注于一种新的转移抑制剂，称为Semaphorin 3F。Semaphorin 3F通常在肺癌中缺失，是一种公认的肿瘤抑制基因，但最近Bielenberg博士和她的导师Michael Klagsbrun博士已经表明Semaphorin 3F与许多肿瘤细胞系的转移呈负相关。当脑信号蛋白3F在转移性细胞中表达时，肿瘤显著地恢复为良性、低血管和包裹的肿瘤表型。这项K01研究计划将跟进这一令人兴奋的发现，并专注于负责Semaphorin 3F抗转移作用的分子机制。我们推测，脑信号蛋白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奖将促进该候选人从讲师到哈佛医学院外科研究系独立调查员的转变，提供生物化学领域的额外培训，包括蛋白质工程和蛋白质纯化，以及使更多的合作和参与区域和国家会议。最重要的是，霍华德特明奖将使这项研究项目继续朝着长期稳定疾病的最终目标发展。