Developing New Mouse Models of ATL for Use in Trials of Targeted Therapies

开发新的 ATL 小鼠模型用于靶向治疗试验

• 批准号: 7244686
• 负责人: Bevin Zimmerman
• 金额: $ 12.69万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-15 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7244686
• 关键词: Acute; Address; Adult; Apoptosis; Apoptotic; CD4 Positive T Lymphocytes; Cause of Death; Cell Line; Cell Proliferation; Cells; Cessation of life; DNA Binding; Deltaretrovirus; Development; Development Plans; Disease regression; Doctor of Philosophy; Drug Delivery Systems; Engraftment; Enrollment; Environment; Five-Year Plans; Gene Expression; Gene Mutation; Genome; Goals; Growth; Human; In Vitro; K-Series Research Career Programs; Knockout Mice; Lead; Licensing; Luciferases; Lymphocyte; Lymphoma; Malignant - descriptor; Malignant Neoplasms; Mentors; Modality; Modeling; Monitor; Mus; NF-kappa B; Ohio; PS341 cpd; Pathway interactions; Phase; Phenotype; Photons; Plasmids; Pre-Clinical Model; Principal Investigator; Proteasome Inhibitor; Proviruses; Public Health; Research; Research Personnel; Research Proposals; Research Training; Resistance; Retrovirology; SCID Mice; Signal Transduction; Students; System; T-Cell Leukemia; T-Cell Transformation; T-Lymphocyte; Taxes; Testing; Therapeutic; Time; Training; Training Programs; Trans-Activators; Transgenic Organisms; Transplantation; Tropical Spastic Paraparesis; Tumor Burden; United States; Universities; Veterinarians; Veterinary Pathology; Viral; Virus; Xenograft procedure; adult leukemia; anti-cancer therapeutic; base; career; cellular targeting; chemotherapy; efficacy evaluation; experience; in vivo; inhibitor/antagonist; leukemia/lymphoma; member; mouse model; neoplastic cell; outcome forecast; post-doctoral training; programs; therapy resistant; tumor

DESCRIPTION (provided by applicant): The Candidate: Dr. Bevin Zimmerman, a licensed veterinarian, is currently enrolled in a veterinary pathology training program and Ph.D. in the Department of Veterinary Biosciences and the Center for Retroviral Research at The Ohio State University (OSU), This K01 SERCA will support three years of her doctoral research (Phase I) and two years of post doctoral training (Phase II). The Environment: Dr. Zimmerman's sponsor, Dr. Michael Lairmore is Chair of the Department of Veterinary Biosciences with expertise in both veterinary pathology and retrovirology. Dr. Lairmore has extensive experience mentoring Ph.D. students and K award trainees. The Training Plan: This five year career development plan is divided into two phases. Phase I of the K award will allow Dr. Zimmerman to devote full time to research training that will culminate in her Ph.D. Phase II will promote Dr. Zimmerman's transition to an independent researcher. The Proposal: The research proposed in this application is focused on HTLV-1, the causative agent of Adult T cell Leukemia/Lymphoma (ATL) and Tropical Spastic Paraparesis (HAM/TSP). The virus is endemic in United States and is present worldwide. The goal of the research application is identify the unique cellular alterations that promote the resistance of ATL to conventional chemotherapy and exploit these cellular alteration using targeted molecules. The efficacy of the targeted therapies will be evaluated both in vitro and in a xenograft mouse model of ATL. Relevance to Public Health: There are currently 20-30 million people infected with HTLV-1 worldwide. Five percent of these people will develop Adult T cell Leukemia. The prognosis for ATL is poor and the median survival time, despite current therapies in less than one year. Our overall goal is identify therapies that may abrogate the resistance to therapy and thus, may eventually prolong survival.

描述（由申请人提供）：候选人：Bevin齐默尔曼博士，一名执业兽医，目前正在参加兽医病理学培训项目，并获得博士学位。在兽医生物科学系和俄亥俄州州立大学（OSU）逆转录病毒研究中心，这K 01 SERCA将支持她三年的博士研究（第一阶段）和两年的博士后培训（第二阶段）。环境：齐默尔曼博士的赞助商，迈克尔Lairmore博士是兽医生物科学系主任与兽医病理学和逆转录病毒学的专业知识。Lairmore博士有丰富的指导博士的经验。学生和K奖学员。培训计划：这个五年职业发展计划分为两个阶段。K奖的第一阶段将使齐默尔曼博士能够全职从事研究培训，最终获得博士学位。第二阶段将促进齐默尔曼博士向独立研究人员的过渡。提案：本申请中提出的研究集中在HTLV-1，成人T细胞白血病/淋巴瘤（ATL）和热带痉挛性轻瘫（HAM/TSP）的病原体。该病毒在美国流行，并在世界范围内存在。该研究应用的目标是确定促进ATL对常规化疗的抗性的独特细胞改变，并使用靶向分子利用这些细胞改变。将在体外和ATL异种移植小鼠模型中评价靶向治疗的疗效。与公共卫生的相关性：目前全球有2000万至3000万人感染HTLV-1。这些人中有5%会发展成成人T细胞白血病。ATL的预后很差，尽管目前的治疗，中位生存时间不到一年。我们的总体目标是确定可能消除对治疗的抵抗的疗法，从而最终可能延长生存期。