Development of Novel Markers for Melanoma Progression

应聘者描述(由申请人提供)：应聘者目前是约翰霍普金斯大学西德尼·基梅尔癌症中心的副研究员，此前曾在约翰霍普金斯大学斯科特·科恩博士的实验室带头努力发现新的胰腺癌标记物和识别胰腺癌侵袭特异性基因。候选人的长期职业目标是开发人类黑色素瘤的早期检测标记物和确定治疗靶点。这项研究建议同时使用指导研究培训期(1-3年)和独立培训期(4-5年)，以便研究人员在Rhoda Alani博士和Scott Kern博士的指导下开发人类黑色素瘤基因发现系统。研究人员已经有了关于黑色素瘤新的诊断/预后肿瘤标志物(HLH转录因子、Id1和原位端粒长度)和治疗靶点(Id1、端粒酶)的早期数据，这些将作为该提案的一部分进行开发。因此，具体目标是：1)使用人类黑色素瘤细胞系和来自疾病进展不同阶段的原发人类黑色素瘤的基因图谱，结合以实验为导向的数据缩减算法，确定黑色素瘤的新标记物和治疗靶点；2)确定Id1在黑素细胞皮损中的诊断/预后意义，及其作为恶性指标和治疗靶点的作用；3)在一项回顾性研究中，评估黑色素瘤档案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果中的诊断/预后作用。研究人员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，而且目前还没有证明可以延长晚期疾病患者预期寿命的治疗方法，预计这些研究将产生很大影响。

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.