Investigation of the Wnt/PCP pathway in human malignant melanoma

人类恶性黑色素瘤中 Wnt/PCP 通路的研究

• 批准号: 7923434
• 负责人: ANDY J CHIEN
• 金额: $ 9.73万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7923434
• 关键词: Address; Affinity Chromatography; Animal Model; Basic Science; Biological Assay; Biological Markers; Biological Models; Biology; Cell Adhesion; Cell Differentiation process; Cell Line; Cell Polarity; Cell Surface Receptors; Cellular biology; Clinical; Complement; Critical Pathways; Cutaneous; Data; Dermatology; Development; Developmental Biology; Diagnosis; Disease; Doctor of Philosophy; Embryo; Embryonic Development; Epitopes; Evaluation; Event; Exhibits; Gene Expression; Genes; Genetic; Goals; Heterogeneity; Human; In Vitro; Incidence; Investigation; Laboratories; Laboratory Study; Lead; Malignant Neoplasms; Mass Spectrum Analysis; Mediating; Mediator of activation protein; Melanoma Cell; Molecular; Moon; Neoplasm Metastasis; Pathogenesis; Pathway interactions; Patients; Physicians; Protein Binding; Proteins; Proteomics; Rana; Refractory Disease; Regulation; Research; Research Personnel; Role; Sampling; Scientist; Series; Signal Pathway; Signal Transduction; Skin; Specimen; Techniques; Testing; Training; Universities; Washington; Wnt proteins; Zebrafish; base; career; cell growth; cell motility; effective therapy; gastrulation; human disease; in vivo; insight; knock-down; loss of function; melanoma; member; novel; oncology; outcome forecast; overexpression; protein complex; protein expression; stem; therapeutic target; tumor

The candidate is an MD-PhD who completed clinical training in dermatology in June 2005 and is now pursuing basic science research with the goal of becoming an independent physician-scientist. The . research is being performed under the sponsorshipof Dr. Randall T. Moon at the University of Washington. The Moon laboratory studies the role of the Wnt signaling pathway in embryonic development and human disease using several model systems, including zebrafish and frogs. The proposed training will prepare the candidate for a career as an independent investigator in skin biology and cutaneous oncology, with a focus on cell biology, cell motility and signal transduction. The incidence of malignant melanoma is increasing faster than that of any other cancer. The lack of effective therapies for metastatic disease reflects our limited understanding of the progression of melanoma and metastasis. Recent studies have implicated the Wnt signaling pathway as an important regulator of both melanoma progression as well as the development of metastatic disease. Wnt's are secreted proteins that bind cell surface receptors to trigger a series of regulated intracellular events that mediate functions including cell growth, cell differentiation, cell adhesion and cell motility. This proposal aims to identify proteins that are important in the regulation of cell motility by the Wnt pathway using a melanoma cell line that exhibits increased motility upon Wnt expression. The proposal will utilize techniques with demonstrated feasibility to test known Wnt proteins for their effects on melanoma cell motility. Next, new candidate Wnt proteins will be identified by the purification of Wnt-related protein complexes in melanoma cells using another established technique. These new proteins will also be tested for effects on cell motility. The issue of molecular heterogeneity seen in melanoma progression will be addressed by evaluating proteins with validated functional significance in the context of different melanoma cell lines, complemented by evaluation of protein expression in patient melanoma samples. Together, these studies will help elucidate the mechanisms underlying the regulation of cell motility by Wnt signaling in the context of malignant melanoma, with the ultimate goal of uncovering protein targets that could serve as biomarkers for prognosis and/or targets for therapeutic manipulation.

该候选人是一名医学博士，于2005年6月完成了皮肤科的临床培训， 追求基础科学研究，目标是成为一名独立的医生科学家。的. 这项研究是在兰德尔·T博士的指导下进行的。月亮在华盛顿大学。 Moon实验室研究了Wnt信号通路在胚胎发育和人类发育中的作用。 疾病使用几个模型系统，包括斑马鱼和青蛙。拟议的培训将使 作为皮肤生物学和皮肤肿瘤学独立研究者的候选人，重点是 细胞生物学、细胞运动和信号转导。 恶性黑色素瘤的发病率比任何其他癌症的发病率增长都快。缺乏 转移性疾病的有效治疗反映了我们对黑色素瘤进展的有限理解 和转移。最近的研究表明，Wnt信号通路是这两个过程的重要调节因子。 黑色素瘤进展以及转移性疾病的发展。Wnt是一种分泌蛋白， 结合细胞表面受体以触发一系列调节细胞内事件，这些事件介导功能，包括 细胞生长、细胞分化、细胞粘附和细胞运动。该提案旨在确定蛋白质， 在通过Wnt途径调节细胞运动性中是重要的 Wnt表达增加运动性。 该提案将利用已证明可行性的技术来测试已知的Wnt蛋白质， 对黑色素瘤细胞运动性的影响。接下来，新的候选Wnt蛋白将通过纯化Wnt蛋白来鉴定。 使用另一种已建立的技术在黑色素瘤细胞中的wnt相关蛋白复合物。这些新蛋白 还将测试对细胞运动性的影响。黑色素瘤中的分子异质性问题 将通过评价在以下背景下具有经验证的功能意义的蛋白质来解决进展： 不同的黑色素瘤细胞系，通过评价患者黑色素瘤中的蛋白质表达进行补充 样品总之，这些研究将有助于阐明细胞调节的潜在机制， 在恶性黑色素瘤的背景下，通过Wnt信号传导的运动，最终目标是揭示蛋白质 可以用作预后的生物标志物和/或治疗操作的靶点。