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招聘上。我于2003年8月26日开始担任NCI调查员，之前在底特律亨利·福特健康系统担任高级职员调查员和皮肤科医生已有4年半的时间。在我在NCI的短时间内，我监督了与我在亨利·福特共事的客座研究员迪瓦卡尔·加内什的持续工作，以及9月22日加入该实验室的生物学家蒋顺林的工作。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。迪瓦卡尔的工作以海报的形式在9月初的泛美色素细胞研究学会年会上展示，我还在会上介绍了亨利·福特关于黑素细胞功能和内耳存活的工作。此外，我还在NIH做了两次演讲，一次是在9月30日的Stanley Group Inter-PI实验室会议上，另一次是在10月7日的NIH色素细胞兴趣小组会议上。 在实验室里，我们已经开始努力开发一种转基因小鼠系，它将允许我们以一种可诱导的方式在黑素细胞中表达体内改变的信号蛋白。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依赖Ras和B-Raf的信号在正常黑素细胞发育和分化中的作用。它还应该为直接检查B-Raf活性在小鼠黑色素瘤进展中的重要性提供基础，这一主题促使我们继续研究，因为发现B-Raf突变在人类黑色素瘤和人类黑色素细胞痣中都非常常见。

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.