The role of the novel interface cell state in melanoma invasion

新型界面细胞状态在黑色素瘤侵袭中的作用

基本信息

批准号：
10591187
负责人：
Miranda Victoria Hunter
金额：
$ 17.3万
依托单位：
SLOAN-KETTERING INST CAN RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10591187
关键词：
Adipocytes Adopted Advisory Committees Basic Cancer Research Biological Models Cancer Biology Cancer Center Cell Communication Cells Chromatin Chromatin Remodeling Factor Cilia Complement Coupled Data Doctor of Philosophy Embryo Ensure Environment Epidermis Epigenetic Process Family Fibroblasts Gene Expression Genes Genetic Goals Growth HMGB2 gene Hallmark Cell Human Human Cell Line Imaging Device Immune Immunotherapy In Vitro Individual Invaded Laboratories Lead Mediating Memorial Sloan-Kettering Cancer Center Mentors Metastatic Melanoma Microscopy Modeling Molecular Phase Postdoctoral Fellow Proliferating Publications Recording of previous events Research Role SHH gene Signal Transduction Skin Survival Rate System Technical Expertise Tissues Transforming Growth Factor beta Tumor Promotion Up-Regulation Work Zebrafish arm cancer genetics career career networking cell behavior cell type clinically relevant combat experimental study follow-up human disease improved in vivo melanoma member neoplastic cell new therapeutic target notch protein novel novel therapeutics prevent programs single-cell RNA sequencing spatial integration success targeted treatment therapeutic target three dimensional cell culture transcription factor transcriptional reprogramming transcriptomics translational cancer research tumor tumor growth tumor microenvironment tumor progression wound healing

项目摘要

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.

项目概要/摘要候选人：我是纪念斯隆凯特琳大学理查德·怀特博士实验室的博士后研究员我的研究生涯主要集中在细胞如何相互作用和沟通，从我的研究开始。博士研究皮肤细胞如何协调胚胎表皮中的快速伤口愈合，并继续我的博士后研究是关于肿瘤和微环境细胞在黑色素瘤侵袭过程中如何相互作用。我最近发表的文章揭示了肿瘤和微环境采用的一种新颖的“界面”细胞状态肿瘤边界的细胞，以纤毛的上调为特征。该提案的目的是确定。最终，我的长期目标是富含纤毛的界面细胞状态对黑色素瘤侵袭的贡献。领导一个独立小组研究肿瘤和微环境细胞如何合作促进为了实现这些目标，我制定了职业计划：（1）开发新的。科学和技术技能；（2）成为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，展示如何了解黑色素瘤进展的分子机制以及黑色素瘤的作用肿瘤微环境（TME）可以导致肿瘤和 TME 细胞之间的相互作用。我最近的工作发现了一种新的富含纤毛的“界面”细胞状态。被肿瘤和肿瘤边界的微环境细胞采用，并发现纤毛是这表明界面细胞状态可能在黑色素瘤中发挥关键作用。为了研究接口在入侵中的作用，我将完成以下具体目标：（1）确定纤毛促进侵袭的机制；（2）研究纤毛基因的表达情况；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，在以下领域拥有重大发现的历史：该研究将在斯隆凯特林研究所的怀特实验室进行。由 Joan Massagué 博士领导的 MSKCC 研究部门是癌症生物学的成员。斯隆凯特琳研究所的遗传学项目，该项目由我的合作导师斯科特·洛博士领导。在我的导师、共同导师、顾问委员会和合作者之间，我组建了一支优秀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向独立过渡期间的科学和专业目标。