Identifying Microenvironmental Factors Regulating Melanoma Promotion and Immune Evasion

项目总结 此SERCA K01应用程序旨在为文兴善博士提供受保护的时间和指导， DVM，博士，成功过渡到终身教职，独立的首席研究员。 文在寅博士是一名兽医和癌症生物学家，他利用基因工程动物模型，具有长期的- 学期目标是建立一个独特的学术肿瘤微环境实验室，包括他的所有研究 技能。在他著名的导师、癌症免疫学家威廉·墨菲博士、博士和 比较病理学家、医学博士Alexander Borowsky和咨询委员会成员 研究和职业发展阶段将巩固文在寅博士在癌症研究方面的专业知识，使用临床前 小鼠模型和最先进的免疫肿瘤学/病理学评估，并准备 成为一名独立的学术研究人员，并建立他的实验室，旨在定义肿瘤 在促进癌症的微环境中，并最终找到新的预防和治疗策略。这个 著名的主办机构，加州大学戴维斯分校，兽医学院和 医学和综合癌症中心为两者的成功提供了良好的环境 研究成就与学术生涯发展。皮肤黑色素瘤是最致命的皮肤 癌症的年发病率在不断增加。而遗传病因和风险因素是 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 免疫回避特征。这项研究试图找出调节肿瘤生长的区域生态位因素。 以及对免疫治疗的反应。根据初步数据，这项赠款申请侧重于 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。这个 这项拟议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)，促进黑色素瘤的促进和免疫逃避，通过产生一个前- 致癌的利基环境。具体目标是：具体目标#1.定义CXCL12信号的作用 AXIS在早期黑色素瘤的促进作用。明确目标2.明确肿瘤微环境CXCL12在 黑色素瘤免疫疗法。这些研究将产生有价值的信息，说明特定的趋化因子如何 信号通路促进遗传易感人群中黑色素瘤的促进和免疫逃避 并将为未来的R01应用程序奠定基础，旨在破译哪些因素在 黑色素瘤的生长和与免疫细胞的致癌通讯网络。总体而言，这个奖项将授予 相对于文在寅博士的竞争力和独立性，特别是在针对肿瘤微环境 成功的黑色素瘤治疗，将为成功的终身教职研究人员奠定基础。

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.