LINEAGE DETERMINATION IN NEURAL CREST DEVELOPMENT

此应用程序的目的是为研究提供支持 培训使我能够成为一名独立的生物医学调查员。 在完成了皮肤科的大部分临床培训后，我计划 将我的研究兴趣从蛋白质化学转移到我的主题 博士培训，通过研究分子和细胞生物学 爱德华实验室神经脊发育的分子生物学研究 B.Ziff博士，纽约大学医学中心生物化学教授， 霍华德·休斯医学院的研究员。在培训期间 期间，L将在皮肤科担任教职 在纽约大学，由医学博士欧文·M·弗里德伯格担任主席。 完成后，我希望成为一名独立资助的终身教职调查员 在一家主要的医疗中心。 该研究项目的目标是了解分子事件 支配着神经脊的早期发育，尤其是黑素细胞。 酪氨酸酶相关蛋白2(Trp-2)基因的调控将是 学习。在小鼠胚胎中，Trp-2是在几天前表达的 黑素细胞终末分化的标志物。表达载体 含有Trp-2启动子的片段将被导入 观察黑素细胞和启动子的活性。DNA元素 对Trp-2表达的重要作用将被确定，促进 早期黑素细胞重要转录因子的鉴定 特定的基因表达。在一项平行研究中，Trp-2启动子将被 用于驱动神经元特异性基因MASH-1的表达。 这些研究的结果可能适用于人类的几个领域 健康。早期基因表达调控因子的筛选 神经脊可能会增加我们对某些先天性疾病的了解 色素减退和耳聋的症状。黑素母细胞具有 在最初从神经迁移的过程中具有巨大的迁移能力 Crest，并了解这种迁移的基础可能会导致新的 对恶性黑色素瘤细胞侵袭性的洞察也是如此。

The purpose of this application is to provide support for research training to enable me to become an independent biomedical investigator. Having completed most of my clinical training in dermatology, I plan to shift my research interests from protein chemistry, the subject of my Ph.D. training, to molecular and cellular biology by studying the molecular biology of neural crest development in the laboratory of Edward B. Ziff, Ph.D., Professor of Biochemistry at NYU Medical Center and an Investigator of the Howard Hughes Medical Institute. During the training period, l will hold a faculty appointment in the Department of Dermatology at NYU, chaired by Irwin M. Freedberg, M.D. When the training period is complete, I hope to be an independently-funded, tenure-track investigator at a major medical center. The goal of the research project is to understand molecular events governing early development of the neural crest, particularly melanocytes. The regulation of the tyrosinase-related protein 2 (TRP-2) gene will be studied. In the mouse embryo, TRP-2 is expressed several days before markers of terminal melanocyte differentiation. Expression vectors containing fragments of the TRP-2 promoter will be transfected into melanocytes and the activity of the promoter observed. DNA elements important for TRP-2 expression will be identified, facilitating the identification of transcription factors important for early melanocyte- specific gene expression. In a parallel study, the TRP-2 promoter will be used to drive the expression of MASH-1, a neuron-specific gene. The results of these studies may be applicable to several areas of human health. Identification of factors responsible for early gene expression in the neural crest may increase our understanding of certain congenital syndromes of hypopigmentation and deafness. Melanoblasts possess tremendous migratory capacity during initial migration from the neural crest, and understanding the basis for this migration may lead to new insights about the invasiveness of malignant melanoma cells as well.