CAREER DEVELOPMENT PROGRAM

描述(申请人提供)：耶鲁大学皮肤癌中的孢子项目专注于两种皮肤癌，基底细胞癌(BCC)和黑色素瘤。目标是对早发性基底细胞癌进行流行病学和遗传学研究(项目1)，建立新的高通量黑色素瘤预后和诊断工具(项目2和4)，并引入治疗黑色素瘤的新的靶向疗法(项目2和3)。新的方法包括全基因组监测黑色素瘤对表观遗传调节剂的反应(项目2)；使用高密度蛋白质微阵列(ProtoArray)来询问黑色素瘤患者血清中的血清学反应(项目4)；以及针对黑色素瘤的新型表观遗传调节剂和免疫调节疗法(分别为项目2和3)。该孢子包括行政管理、标本资源和生物信息学/生物统计学核心，以支持孢子调查人员的研究。提出了发展研究和职业发展奖计划。皮肤癌耶鲁大学孢子中心将是耶鲁综合癌症中心(YCCC)、耶鲁纽黑文医院以及皮肤科、病理学和流行病学/公共卫生部门不可或缺的一部分，这些部门将共同提供孢子活动所需的患者群体、标本和其他资源和支持系统。耶鲁大学医学院院长和基督教青年会主任/皮肤科主席都做出了充分的承诺，支持孢子的费用分摊计划。预期的主要翻译成果有：a)旨在减少早期和全部基底细胞癌发病率的预防干预指南，这将减少最常见皮肤癌的管理成本；b)采用新的分子工具来评估对新型表观遗传学修饰剂的反应；c)采用新的方法来评估黑色素瘤患者的血清标志物；d)应用新的方法使黑色素瘤的化疗和免疫治疗个性化；e)建立皮肤癌的综合数据库，其中包括样本跟踪、临床信息、高通量蛋白质组学和基因组学。数据库程序将与caBIG兼容，并将在网上提供，以造福于更广泛的研究人员和临床医生社区；f)创建新的转译生物信息学工具(预测统计和人工智能)，需要分析来自不同来源和不同平台的高度复杂的全球信息。

DESCRIPTION (provided by applicant): The Yale SPORE in Skin Cancer program is focused on two skin cancers, basal cell carcinoma (BCC) and melanoma. The goals are to conduct epidemiologic and genetic studies on early onset basal cell carcinoma (Project 1), establish novel high-throughput prognostic and diagnostic tools for melanomas (Projects 2 and 4), and introduce novel targeted therapies to treat melanoma (Projects 2 and 3). The new approaches include genome-wide monitoring of melanoma tumor responses to epigenetic modifiers (Project 2); the use of high-density protein microarrays (ProtoArrays) to interrogate serological responses in sera from melanoma patients (Project 4); and novel epigenetic modifier and immune modulation therapy for melanoma (Projects 2 and 3, respectively). The SPORE includes Administration, Specimen Resource and Bioinformatics/Biostatistics Cores to support the studies of SPORE investigators. Developmental Research and Career Development Award Programs are proposed. The Yale SPORE in Skin Cancer will be an integral part of the Yale Comprehensive Cancer Center (YCCC), Yale New Haven Hospital, and the Dermatology, Pathology and Epidemiology/Public Health Departments that collectively will provide the patient populations, specimens and other resources and support systems needed for the SPORE activities. There is a full commitment from the Dean of Yale School of Medicine and the Director of the YCCC/Chairman of Dermatology to support the SPORE with a plan for cost sharing. The major Translational Results expected are: a) Guidelines for preventive interventions aimed at reducing the incidence of early and total BCC that will diminish the management costs of the most common skin cancer; b) The introduction of new molecular tools for assessing responses to novel epigenetic modifiers; c) The introduction of new ways of assessing melanoma patients employing serological markers; d) The application of new approaches to personalize melanoma chemo- and immuno- therapy; e) The establishment of a composite databases for skin cancers that includes specimens tracking, clinical information, high throughput proteomics and genomics. The database program will be compatible with caBIG and will be available on the web for the benefit of the wider community of investigators and clinicians; f) The creation of new translational bioinformatics tools (predictive statistics and artificial intelligence) required to analyze global and highly complex information derived from different sources and different platforms.