LINEAGE DETERMINATION IN NEURAL CREST DEVELOPMENT

本申请的目的是为研究提供支持 培训，使我成为一名独立的生物医学调查员。 在完成了大部分皮肤科的临床培训后，我计划 将我的研究兴趣从蛋白质化学转移，我的研究主题是 博士培训，分子和细胞生物学，通过研究 神经嵴发育的分子生物学 B。Ziff博士，纽约大学医学中心生物化学教授， 霍华德休斯医学研究所的研究员。培训期间 在此期间，我将在皮肤科担任教职 在纽约大学，由欧文M. Freedberg，医学博士当培训期为 我希望成为一名独立资助的终身研究员 一家大型医疗中心 该研究项目的目标是了解分子事件 控制神经嵴的早期发育，特别是黑色素细胞。 酪氨酸酶相关蛋白2（TRP-2）基因的调控将是 研究了在小鼠胚胎中，TRP-2在胚胎发育前几天表达， 终末黑素细胞分化的标志物。表达载体 将含有TRP-2启动子片段的质粒转染入 观察黑素细胞和启动子的活性。DNA元件 重要的TRP-2表达将被确定，促进 对早期黑素细胞重要转录因子的鉴定- 特异性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 健康鉴定负责早期基因表达的因素， 神经嵴可以增加我们对某些先天性 色素减退和耳聋的综合征。成黑素细胞具有 在最初从神经迁移过程中巨大的迁移能力 波峰，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的侵袭性也有了新的认识。

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.