Regulation of Melanocyte Development and Differentiation

该项目的主要工作集中在实验室设置和人员获取上。我于2003年8月26日开始担任NCI研究员，此前曾在底特律的亨利福特卫生系统担任高级研究员和皮肤科医生4年半。我在国家癌症研究所工作的时间很短，但我一直在监督访问学者迪瓦卡尔·甘内什（Diwakar Ganesh）的工作，他曾在亨利福特与我共事，我还监督了9月22日加入实验室的生物学家蒋顺林（Shunlin Jiang）的工作。我们已经为实验室采购了主要设备，并启动了对我们的未来至关重要的实验室流程。9月初，在泛美色素细胞研究学会的年会上，迪瓦卡的研究成果以海报的形式展示了出来。在那次会议上，我还发表了一篇演讲，介绍了亨利福特在内耳中黑素细胞功能和存活方面的研究成果。此外，我还在NIH做了两次演讲，一次是9月30日在斯坦利小组PI实验室间会议上，另一次是10月7日在NIH色素细胞兴趣小组上。 在实验室中，我们已经开始开发一种转基因小鼠品系，这将使我们能够在体内黑素细胞中以可诱导的方式表达改变的信号蛋白。我们还开始研究信号蛋白B-Raf在常用的黑素细胞和黑色素瘤细胞系中的表达和突变状态。这种方法的结合应该有助于我们更多地了解Ras和B-Raf依赖性信号在正常黑素细胞发育和分化中的作用。它也应该提供一个基础，直接检查B-Raf活性在小鼠黑色素瘤进展中的重要性，一个主题，我们已经被提示追求的基础上发现，B-Raf突变是非常常见的人类黑色素瘤和人类黑色素细胞痣。

The primary effort on this project has been focused upon laboratory setup and personnel acquisition. I began as an NCI Investigator on August 26, 2003, having previously been a Senior Staff Investigator and dermatologist at the Henry Ford Health System in Detroit for 4 1/2 years. In the short time that I have been at NCI, I have supervised the continued work of a Visiting Fellow, Diwakar Ganesh, who worked with me at Henry Ford, as well as the work of Shunlin Jiang, a biologist who joined the lab on September 22. We have procured major equipment for the lab and initiated lab processes that will be important for our future. Diwakar's work was presented in poster form in early September at the annual meeting of the Pan-American Society for Pigment Cell Research, where I also presented a talk on work done at Henry Ford about melanocyte function and survival in the inner ear. Additionally, I have made two presentations at NIH, one to the Stanley group inter-PI lab meeting on September 30 and one to the NIH Pigment Cell Interest Group on October 7. In the lab, we have begun work to develop a transgenic mouse line that will permit us to express in an inducible manner altered signaling proteins in vivo in melanocytes. We have also begun to investigate the expression and mutation status of the signaling protein B-Raf in commonly used melanocyte and melanoma cell lines. This combination of approaches should help us understand more about the role of Ras- and B-Raf-dependent signaling in normal melanocyte development and differentiation. It should also provide a foundation for examining directly the importance of B-Raf activity in melanoma progression in mice, a topic we have been prompted to pursue based upon the finding that B-Raf mutations are extremely common in both human melanomas and human melanocytic nevi.