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

• 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
• 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

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.

项目摘要/摘要 候选人：我是斯隆·凯特林纪念馆理查德·怀特博士实验室的博士后研究员 癌症中心。我的研究生涯一直专注于细胞如何相互作用和交流，从我的 关于皮肤细胞如何协调胚胎表皮伤口快速愈合的博士研究，并在继续 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都采用的一种新的“界面”细胞状态 肿瘤边界的细胞，以纤毛上调为特征。这项提案的目标是确定 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促进 黑色素瘤进展。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)成为有效的领导者和导师；(3)扩大我的职业关系网 顾问和合作者；(4)成功地向独立角色过渡。 研究：黑色素瘤治疗的最新进展，包括靶向治疗和免疫治疗， 演示如何理解黑色素瘤进展的分子机制以及 肿瘤微环境(TME)可以带来新的治疗方法。肿瘤与TME细胞的相互作用 通常会促进黑色素瘤的进展。我最近的工作发现了一种新型的富含纤毛的细胞状态 被肿瘤和肿瘤边界的微环境细胞所采用，并发现纤毛是 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 进步。为了研究界面在入侵中的作用，我将完成以下具体目标：(1) 确定纤毛促进入侵的机制；(2)研究纤毛基因是如何表达的 规范；(3)确定建立接口单元状态的机制。 环境：在指导阶段，拟议的工作将在斯隆·凯特林纪念馆完成 癌症中心(MSKCC)，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·凯特琳研究所的怀特实验室进行 由Joan Massagué博士领导的MSKCC研究部门。怀特实验室是癌症生物学协会的成员 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Scott Lowe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，我组建了一支出色的团队 他们将指导这项工作，并协助实现我的 在向独立过渡期间的科学和专业目标。