BLRD Research Career Scientist Award Application

反映人类癌症的小鼠模型是基础科学翻译的重要工具 临床治疗的新发现。然而，在过去几年中，快速发展的技术需要 进一步改进当前的方法，使模型更适合于稳健的翻译 应用程序提供一致的信息，以满足患者的需求。我的第一个退伍军人荣誉奖的焦点 是关于体外和体内代谢改变对黑色素瘤发生的贡献。来自这些的结果 早期的研究为我们提供了对我们理性构思的战略的理解和知识 我们目前退伍军人事务部的工作假设。近年来，人们对分子的了解很多。 黑色素瘤的病理和治疗已取得重大进展，但仍处于晚期 黑色素瘤仍然是最难治愈的癌症之一，有很高的转移倾向。独一无二的 我们小组建立的小鼠模型中，正常神经元受体的异位表达， 代谢性谷氨酸受体(GRM1)，在正常黑素细胞中导致一致的，广泛分布的 黑素细胞病变的发展和转移到包括肺和脑在内的多个器官，两 人类黑色素瘤的常见转移部位。我们的重点是利用创新模式 模拟人类黑色素瘤的脑转移，以扩大、改善和改变 用于翻译研究的哺乳动物肿瘤模型。完成我们提议的调查是至关重要的 朝着建立根本重要和相关的人类癌症动物模型迈出一步 改善和挽救癌症患者的生命。

Mouse models reflecting human cancers are important tools towards the translation of basic science discoveries to clinical therapies. However, rapidly evolving technologies within the last few years require further refining current approaches that enable models to be more suitable in robust translational applications to provide consistent information to meet patients’ needs. The focus of my first VA Merit award was on the contributions of altered metabolisms to melanomagenesis in vitro and in vivo. Results from these earlier studies have provided understanding and knowledge in the rational conceived strategy of our working hypothesis for our current VA Merit. In recent years, much has been learned about the molecular pathology of melanoma and significant progress has been made towards its treatment, yet late-stage melanoma still remains one of the least curable cancers with high metastatic propensity. The unique mouse models established by our group where the ectopic expression of a normal neuronal receptor, metabotropic glutamate receptor (GRM1), in normal melanocytes leads to consistent, wide-spread development of melanocytic lesions and metastasis to various organs including the lung and brain, two common metastatic sites for human melanoma. Our focus is to take advantage of the innovative model that mimic human melanoma with brain metastases to expand, improve, and transform the utility of mammalian tumor models for translational research. Completion of our proposed investigation is an essential step towards establishing fundamentally important and relevant animal models of human cancer that will improve and save cancer patient lives.