Identifying Microenvironmental Factors Regulating Melanoma Promotion and Immune Evasion

识别调节黑色素瘤促进和免疫逃避的微环境因素

基本信息

批准号：
10399646
负责人：
Hyeongsun Moon
金额：
$ 10.49万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-01 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10399646
关键词：
Advisory Committees Affect Animal Model Applications Grants Award Behavior Biological Models CD8-Positive T-Lymphocytes CTLA4 gene CXCL12 gene CXCR4 gene California Cancer Patient Cell physiology Cells Characteristics Clinical Clinical Trials Committee Members Communication Complex Comprehensive Cancer Center Cutaneous Cutaneous Melanoma Data Development Doctor of Philosophy Economic Burden Environment Epidermis FOXP3 gene Foundations Future Genes Genetic Genetic Engineering Genetic Predisposition to Disease Genetically Engineered Mouse Goals Grant Human Immune Immune Evasion Immune system Immunologic Surveillance Immunologist Immunooncology Immunotherapy Incidence Institutes Knockout Mice Knowledge Leukocytes Malignant - descriptor Malignant Neoplasms Measures Mediating Melanocytic Neoplasm Melanoma Cell Memory Mentors Mentorship Modeling Molecular Moon Mus Myeloid-derived suppressor cells Oncogenic Outcome Outcome Study Pathologist Pathology Pathway interactions Patients Play Population Preventive treatment Principal Investigator Process Regulatory T-Lymphocyte Research Research Personnel Resistance Risk Factors Role Signal Pathway Signal Transduction Site Skin Skin Cancer Specimen Stratum Basale Stromal Cell-Derived Factor 1 T-Lymphocyte The Cancer Genome Atlas Therapeutic Time Tissues Tumor Promoters Tumor Promotion Tumor-Derived Tumor-infiltrating immune cells Ultraviolet Rays Universities Veterinarians Veterinary Medicine Veterinary Schools anti-PD-1 anticancer research base cancer cell career development chemokine comparative conditional knockout driver mutation evidence base genetic risk factor health economics immune checkpoint immune checkpoint blockers immunogenic in vivo medical schools melanocyte melanoma migration mortality mouse model multiplexed imaging neoplasm immunotherapy neoplastic cell novel pre-clinical prevent public health relevance receptor recruit research and development response skills stem cell niche stem cells tenure track transcriptome sequencing tumor tumor microenvironment tumor-immune system interactions tumorigenic

项目摘要

PROJECT SUMMARY This SERCA K01 application aims to provide the protected time and mentorship for Dr. Hyeongsun Moon, DVM, PhD to make the successful transition to a tenure-track, independent principal investigator. Dr. Moon is a veterinarian and cancer biologist that utilizes genetically engineered animal models with a long- term goal to establish a unique academic tumor microenvironment lab that encompasses all of his research skills. Under the guidance of his well-established mentors, cancer immunologist, Dr. William Murphy, PhD and comparative pathologist, Dr. Alexander Borowsky, MD and advisory committee members, the mentored research and career development period will solidify Dr. Moon’s expertise in cancer research using preclinical mouse models and the state-of-the-art immuno-oncology/pathology assessments, and prepare himself to become an independent academic researcher and establish his lab which aims to define the tumor microenvironment in cancer promotion, and ultimately find novel preventative and therapeutic strategies. The prestigious host institute, the University of California at Davis, the School of Veterinary Medicine and School of Medicine, and the Comprehensive Cancer Center, provides an excellent environment for both successful research accomplishment and academic career development. Cutaneous melanoma is the deadliest skin cancer with a continuous increase in its annual incidence rate. While genetic etiologies and risk factors are well-known, little is known about the mechanisms behind the factors governing melanoma promotion including immune evasive characteristics. This study seeks to identify regional niche factors regulating tumor outgrowth and response to immunotherapy. Based on preliminary data, this grant application focuses on the microenvironmental C-X-C motif chemokine 12 (CXCL12) signaling axis and its role in these processes. The central hypothesis of the proposed study is that microenvironmental CXCL12, also known as stromal cell- derived factor 1 (SDF-1), facilitates melanoma promotion and immune evasion via generating a pro- tumorigenic niche environment. The specific aims are: Specific Aim #1. Define the role of CXCL12 signaling axis in early melanoma promotion. Specific Aim #2. Define the role of tumor microenvironmental CXCL12 in melanoma immunotherapy. These studies will generate valuable information on how a specific chemokine signaling pathway promotes melanoma promotion and immune evasion in a genetically susceptible population and will lay the foundation for a future R01 application aimed at deciphering what factors play a critical role in melanoma outgrowth and oncogenic communication networks with immune cells. Overall, this award will grant competitiveness and independence to Dr. Moon particularly on targeting the tumor microenvironment for successful melanoma treatment and will lay the foundation towards a successful tenure-track researcher.

项目概要此 SERCA K01 申请旨在为 Hyungsun Moon 博士提供受保护的时间和指导， DVM、博士成功过渡为终身教授、独立首席研究员。 Moon 博士是一位兽医和癌症生物学家，他利用基因工程动物模型进行了长期研究。学期目标是建立一个独特的学术肿瘤微环境实验室，涵盖他的所有研究在他的知名导师、癌症免疫学家 William Murphy 博士和博士的指导下。比较病理学家、医学博士 Alexander Borowsky 博士和咨询委员会成员，研究和职业发展期将巩固 Moon 博士利用临床前研究在癌症研究方面的专业知识小鼠模型和最先进的免疫肿瘤学/病理学评估，并准备好成为一名独立的学术研究员并建立他的实验室，旨在定义肿瘤癌症促进的微环境，并最终找到新的预防和治疗策略。著名的主办机构，加州大学戴维斯分校、兽医学院和兽医学院医学和综合癌症中心为两者的成功提供了良好的环境研究完成和学术职业发展皮肤黑色素瘤是最致命的皮肤。癌症的年发病率持续增加，而遗传病因和危险因素却在不断增加。众所周知，人们对黑色素瘤促进因素背后的机制知之甚少，包括本研究旨在确定调节肿瘤生长的区域生态位因素。根据初步数据，本次拨款申请重点关注微环境 C-X-C 基序趋化因子 12 (CXCL12) 信号轴及其在这些过程中的作用。该研究的中心假设是微环境CXCL12，也称为基质细胞- 衍生因子 1 (SDF-1)，通过产生促黑色素瘤促进和免疫逃避具体目标是：明确 CXCL12 信号传导的作用。具体目标 #2 定义肿瘤微环境 CXCL12 在早期黑色素瘤促进中的作用。这些研究将产生关于特定趋化因子如何发挥作用的有价值的信息。信号通路促进遗传易感人群中黑色素瘤的发生和免疫逃避并将为未来的 R01 应用奠定基础，旨在破译哪些因素在总的来说，该奖项将授予黑色素瘤生长和与免疫细胞的致癌通讯网络。文博士的竞争力和独立性，特别是针对肿瘤微环境成功的黑色素瘤治疗将为成为一名成功的终身教授奠定基础。