The role of the novel interface cell state in melanoma invasion

项目总结/摘要 候选人：我是纪念斯隆凯特琳学院理查德白色博士实验室的博士后研究员 癌症中心我的研究生涯主要集中在细胞如何相互作用和交流，从我的研究开始。 博士研究皮肤细胞如何协调胚胎表皮的快速伤口愈合，并继续 我的博士后研究是关于黑色素瘤侵袭过程中肿瘤和微环境细胞如何相互作用。 我最近的出版物揭示了肿瘤和微环境所采用的一种新的“界面”细胞状态 肿瘤边界的细胞，通过纤毛的上调来区分。本提案的目的是确定 富含纤毛的界面细胞状态对黑色素瘤侵袭的贡献。最终，我的长期目标是 领导一个独立的小组，研究肿瘤和微环境细胞如何合作， 黑素瘤进展。为了实现这些目标，我制定了一个职业规划：（1）开发新的 科学和技术技能;（2）成为一个有效的领导者和导师;（3）扩展我的专业网络， 顾问和合作者;（4）成功过渡到独立的角色。 研究：治疗黑色素瘤的最新进展，包括靶向治疗和免疫治疗， 展示了如何理解黑色素瘤进展的分子机制和黑色素瘤的作用， 肿瘤微环境（TME）可以导致新的治疗方法。肿瘤与TME细胞之间的相互作用 往往会促进黑色素瘤的进展。我最近的工作确定了一种新的纤毛丰富的“界面”细胞状态 通过肿瘤和微环境细胞在肿瘤边界，并发现纤毛是必需的， 黑色素瘤侵袭这表明界面细胞状态可能在黑色素瘤中起关键作用 进展为了研究界面在入侵中的作用，我将实现以下具体目标：（1） 确定纤毛促进侵袭的机制;（2）研究纤毛基因表达如何影响细胞的侵袭能力。 调节;（3）确定建立界面细胞状态的机制。 环境：在指导阶段，拟议的工作将在纪念斯隆凯特琳完成 癌症中心（MSKCC）是世界领先的癌症中心之一，在 癌症生物学这项研究将在斯隆凯特琳研究所的白色实验室进行， MSKCC的研究部门，由Joan Massagué博士领导。白色实验室是癌症生物学 和斯隆凯特琳研究所的遗传学项目，这是一个由我的共同导师斯科特·洛博士领导的项目。 在我的导师、共同导师、顾问委员会和合作者之间，我组建了一个出色的团队 基础和转化癌症研究的专家将指导这项工作，并协助实现我的目标。 在向独立过渡期间的科学和专业目标。

PROJECT SUMMARY/ABSTRACT Candidate: I am a postdoctoral fellow in the laboratory of Dr. Richard White at Memorial Sloan Kettering Cancer Center. My research career has focused on how cells interact and communicate, beginning with my PhD research into how skin cells coordinate rapid wound healing in the embryonic epidermis, and continuing into my postdoctoral research on how tumor and microenvironment cells interact during melanoma invasion. My recent publication uncovered a novel “interface” cell state adopted by both tumor and microenvironment cells at the tumor boundary, distinguished by upregulation of cilia. The objective of this proposal is to determine the contribution of the cilia-enriched interface cell state to melanoma invasion. Ultimately, my long-term goal is to lead an independent group studying how tumor and microenvironment cells cooperate to promote melanoma progression. To accomplish these goals, I have developed a career plan to: (1) develop new scientific and technical skills; (2) become an effective leader and mentor; (3) extend my professional network of advisors and collaborators; (4) successfully transition to an independent role. Research: Recent advances in treating melanoma, including targeted therapies and immunotherapy, demonstrate how an understanding of the molecular mechanisms of melanoma progression and the role of the tumor microenvironment (TME) can lead to novel therapeutics. Interactions between tumor and TME cells often promote melanoma progression. My recent work identified a novel cilia-enriched “interface” cell state adopted by tumor and microenvironment cells at the tumor boundary, and found that cilia are required for melanoma invasion. This indicates that the interface cell state may have a critical role in melanoma progression. To investigate the role of the interface in invasion, I will accomplish the following specific aims: (1) determine the mechanism by which cilia promote invasion; (2) investigate how cilia gene expression is regulated; (3) identify the mechanisms that establish the interface cell state. Environment: During the mentored phase, the proposed work will be completed at Memorial Sloan Kettering Cancer Center (MSKCC), one of the world’s leading cancer centers with a history of major discoveries in cancer biology. The research will be performed in the White laboratory within Sloan Kettering Institute, the research arm of MSKCC, led by Dr. Joan Massagué. The White laboratory is a member of the Cancer Biology and Genetics Program within Sloan Kettering Institute, a program led by my co-mentor Dr. Scott Lowe. Between my mentor, co-mentor, advisory committee, and collaborators, I have assembled an outstanding team of experts in basic and translational cancer research who will guide this work and assist with achieving my scientific and professional goals during the transition to independence.