BLRD Research Career Scientist Award Application

BLRD 研究职业科学家奖申请

基本信息

批准号：
10701238
负责人：
Suzie Chen
金额：
--
依托单位：
VA NEW JERSEY HEALTH CARE SYSTEM
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-04-01 至 2028-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10701238
关键词：
Academia American Association for the Advancement of Science Animal Model Appointment Area Automobile Driving Award Basic Science Biological Availability Biological Models Biology Brain Cancer Institute of New Jersey Cancer Patient Cancer Therapy Evaluation Program Cell surface Central Nervous System Characteristics Chemicals Clinic Clinical Clinical Trials Collaborations Communities Cytochrome P450 Development Discipline Disease Ectopic Expression Epithelial Cells Etiology Experimental Models FDA approved Fellowship GRM1 gene Glioma Glutamates Goals Grant Half-Life Health Human In Vitro Industry Collaboration Investigation Joints Knowledge Laboratories Laboratory Finding Learning Legal patent Lesion Ligands Longitudinal Studies Lung Malignant Neoplasms Malignant neoplasm of brain Medical center Memory Metabolism Metabotropic Glutamate Receptors Metastatic malignant neoplasm to brain Modeling Modification Multi-Institutional Clinical Trial Mus Mutation National Cancer Institute Neoplasm Metastasis Neurons Oncogenic Oranges Organ Patient Recruitments Patients Peer Review Pennsylvania Pharmacotherapy Pharmacy Schools Phase Physicians Postdoctoral Fellow Probability Prodrugs Prognostic Marker Property Publications Renal carcinoma Research Research Personnel Research Project Grants Research Support Rewards Riluzole Role Scientist Secure Signal Pathway Signal Transduction Site Small Business Innovation Research Grant System Technology Testing Toxic effect Transgenic Mice Translating Translational Research Translations Trustees Universities Work amyotrophic lateral sclerosis therapy anticancer research biomarker identification career cell transformation distinguished professor drug discovery experimental study glutamatergic signaling human model improved in vivo innovation inter-individual variation interest malignant breast neoplasm melanocyte melanoma melanomagenesis metabotropic glutamate receptor type 1 molecular pathology mouse model pre-clinical prevent programs receptor screening therapeutically effective tool translational applications translational model tumor

项目摘要

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.

反映人类癌的鼠标是基础科学翻译的重要工具发现临床疗法。但是，在过去几年内快速发展的技术进一步完善当前方法，使模型更适合于稳健的翻译提供一致信息以满足患者需求的申请。我的第一个VA功绩奖的重点在体外和体内改变了代谢对黑色素作用的贡献。这些结果早期的研究提供了我们的理性构想策略中的理解和知识为我们当前的VA功绩进行工作假设。近年来，关于分子的知识已有很多黑色素瘤的病理和对治疗的重大进展，但后期黑色素瘤仍然是具有高转移性前景的最不可治愈的癌症之一。独特我们组建立的小鼠模型，其中正常神经元接收器的生态表达代谢性谷氨酸受体（GRM1），在正常黑素细胞中导致一致，广泛发育黑素细胞病变和向包括肺和大脑在内的各种器官的转移，两个人黑色素瘤的常见转移部位。我们的重点是利用创新模型模仿人类黑色素瘤与脑转移，以扩展，改善和改变转化研究的哺乳动物肿瘤模型。完成我们提议的调查是必不可少的迈向建立根本重要且相关的人类癌症动物模型的一步改善并挽救癌症患者的生命。