Development of Novel Markers for Melanoma Progression

描述（由申请人提供）：该候选人目前是约翰霍普金斯Sidney Kimmel癌症中心的研究助理，此前曾在约翰霍普金斯Scott克恩博士的实验室中率先努力发现新的胰腺癌标志物并鉴定胰腺癌中的侵袭特异性基因。候选人的长期职业目标是开发早期检测标记物并确定人类黑色素瘤的治疗靶点。本研究计划使用指导研究培训期（1-3年）和独立培训期（4-5年），以便研究者在Rhoda Alani和Scott克恩博士的指导下开发人类黑色素瘤的基因发现系统。研究者已经有了关于黑色素瘤中有希望的新的诊断/预后黑色素瘤肿瘤标志物（HLH转录因子，Id 1和原位端粒长度）和治疗靶点（Id 1，端粒酶）的早期数据，这些将作为本提案的一部分开发。因此，具体的目的是：1）使用来自疾病进展的不同阶段的人黑素瘤细胞系和原发性人黑素瘤的基因谱分析结合实验导向的数据简化算法来鉴定黑素瘤的新标志物和治疗靶点; 2）确定黑素细胞病变中Id 1表达的诊断/预后意义及其作为恶性肿瘤和治疗靶点的指示剂的效用; 3）在一项回顾性研究中，评估黑色素瘤存档样本中的原位端粒长度，并确定端粒长度在预测黑色素瘤生物学结局中的诊断/预后效用。研究者的总体目标是从胰腺癌的分子特征研究过渡到人类黑色素瘤的类似研究。由于黑色素瘤是美国增长最快的恶性肿瘤，并且没有任何治疗方法可以延长晚期疾病患者的预期寿命，因此预计这些研究将产生很大的影响。

DESCRIPTION (provided by applicant): The candidate is currently a Research Associate in the Sidney Kimmel Cancer Center at Johns Hopkins who has previously spearheaded efforts towards discovery of new pancreatic cancer markers and the identification of invasion-specific genes in pancreatic cancers in the laboratory of Dr. Scott Kern at Johns Hopkins. The long-term career objectives of the candidate are to develop early detection markers and identify therapeutic targets for human melanoma. This research proposal uses both a mentored research training period (years 1-3) and an independent training period (years 4-5) in order for the investigator to develop gene discovery systems for human melanoma under the guidance of Drs. Rhoda Alani and Scott Kern. The investigator already has early data on promising new diagnostic/prognostic melanoma tumor markers (the HLH transcription factor, Id1 and in-situ telomere length) and therapeutic targets (Id1, telomerase) in melanoma and those will be developed as part of this proposal. The specific aims are, therefore: 1) to identify novel markers and therapeutic targets for melanoma using gene profiling of human melanoma cell lines and primary human melanomas from varying stages of disease progression in combination with experiment-oriented data reduction algorism; 2) to determine the diagnostic/prognostic significance of Id1 expression in melanocytic lesions and its utility as an indicator of malignancy and therapeutic target; 3) To evaluate in-situ telomere lengths in archival samples of melanomas and determine the diagnostic/prognostic utility of telomere length in predicting biologic outcomes of melanomas in a retrospective study. The overall goal of the investigator is to transition from research in the molecular characterization of pancreatic cancers to analogous studies in human melanoma. Since melanoma is the fastest growing malignancy in the U.S. and there are no therapies that have been shown to increase life expectancy for patients with advanced disease, it is anticipated that these studies will be of high impact.