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：
10188901
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 2026-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10188901
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.

项目摘要该SERCA K01应用程序旨在为Hyeongsun Moon博士提供受保护的时间和指导， DVM博士，将成功过渡到终身轨道，独立的首席研究员。 Moon博士是一位兽医和癌症生物学家，它Utilizz统一了基因研究的动物模型，建立一个独立肿瘤微环境实验室的术语目标，该实验室涵盖了他的所有研究技能。比较病理学家，医学博士亚历山大·博罗斯基（Alexander Borowsky）博士和咨询委员会成员研究与职业发展期，巩固了Moon博士在癌症研究方面使用临床前的专业知识鼠标穆斯和最先进的免疫 - 神学/病理评估，并准备自己成为不适的学术研究人员，并建立旨在定义肿瘤的实验室癌症促进的微环境，最终发现了新颖的预防和治疗策略著名的东道国研究所，加利福尼亚大学戴维斯分校，兽医学院和学校医学和综合性癌症中心为两者都成功提供了一个绝佳的环境研究成就和学术职业发展。癌症不断增加IS年度发病率。众所周知的，关于促进黑色素瘤的因素背后的机制知之甚少免疫发射特征。和对免疫疗法的反应。微环境C-X-C基趋化趋化因子12（CXCL12）信号轴，在这些过程中起作用支撑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），通过产生促进性，促进黑色素瘤促进和免疫逃避肿瘤利基环境。早期黑色素瘤的轴＃2。黑色素瘤免疫疗法将产生有关特定趋化因子的宝贵信息信号传导途径促进遗传易感人群中的黑色素瘤促进和免疫电子并将为未来的R01应用程序奠定基础，旨在破译哪些因素在黑色素瘤的生长和具有免疫细胞的致癌通信网络。竞争和独立于月亮博士，尤其是针对肿瘤微伏特成功的黑色素瘤治疗，并将成为基金会城镇成功的终身研究员。