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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

基本信息

批准号：
7682987
负责人：
ANDY J CHIEN
金额：
$ 13.22万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-08-15 至 2011-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7682987
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

项目摘要

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月完成了皮肤科临床培训，现在是