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

Semaphorin 3F：结构、功能和抗转移活性

• 批准号: 7434555
• 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/7434555
• 关键词: Andro-Diane; 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; Operative Surgical Procedures; 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; neoplastic cell; neovascularization; novel; novel therapeutics; programs; protein purification; size; therapeutic angiogenesis; tool; tumor; Andro-Diane; 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; Operative Surgical Procedures; 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; neoplastic cell; neovascularization; novel; novel therapeutics; programs; protein purification; size; 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博士是儿童医院外科研究部和哈佛医学院的教练，由血管生成研究领域的先驱犹大·福克曼（Judah Folkman）主持。作为血管生物学计划的一部分，癌症生物学家Bielenberg博士专门研究转移研究，是恶性肿瘤细胞从体内一个部位传播到另一个部位。申请人的长期职业目标是留在学术研究中，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，我们才能希望开发出更好的工具来抗击这种疾病。 Bielenberg博士先前已经研究了干扰素参与抗血管生成疗法的分子机制，内源性干扰素-Beta在皮肤婴儿血管瘤的涉及中的作用，以及鉴定和抗肿瘤的抗肿瘤活性，对血管内无内膜生长因子的自然可溶性受体（称为溶剂）所谓的溶液溶液。 Bielenberg博士被晋升为讲师，专注于一种新型的转移抑制剂，称为Semaphorin 3F。 Semaphorin 3F通常在肺癌中被删除，并且是推定的肿瘤抑制基因，但最近Bielenberg博士和她的导师Michael Klagsbrun博士表明，Semaphorin 3F与许多肿瘤细胞系中的转移呈负相关。当在转移细胞中表达词磷酸蛋白酶3F时，肿瘤明显恢复为良性，血管下和封装的肿瘤表型。这项K01研究建议将跟进这一令人兴奋的发现，并关注负责闪光蛋白3F抗转移性作用的分子机制。我们假设Semaphorin 3F将调节转移性级联反应的关键步骤，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新的治疗策略。 K01奖将促进该候选人从哈佛医学院外科研究系的独立研究人员的过渡，通过在包括蛋白质工程和蛋白质纯化在内的生物化学领域提供额外的培训，并促进其他合作和参与区域和国民会议。最重要的是，霍华德·特林（Howard Temin）奖将使该研究项目的延续达到长期稳定疾病的最终目标。