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

描述（由申请人提供）：候选人：Bevin Zimmerman博士，一名有执照的兽医，目前在俄亥俄州立大学（OSU）兽医生物科学系和逆转录病毒研究中心就读兽医病理学培训计划和博士学位，该K01 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：Dr. Zimmerman的赞助人，Dr. Michael Lairmore是兽医生物科学系的主席，在兽医病理学和逆转录病毒学方面都有专业知识。Lairmore博士在指导博士生和K奖学员方面有着丰富的经验。培训计划：这个五年的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身心地投入到研究培训中，并最终获得博士学位。第二阶段将促进齐默尔曼博士向独立研究员的过渡。提案：本申请拟研究成人T细胞白血病/淋巴瘤（ATL）和热带痉挛性截瘫（HAM/TSP）的病原体HTLV-1。这种病毒在美国是地方性的，在全世界都存在。该研究申请的目标是确定促进ATL对常规化疗耐药的独特细胞改变，并利用靶向分子利用这些细胞改变。靶向治疗的效果将在体外和异种移植ATL小鼠模型中进行评估。与公共卫生的相关性：目前全世界有2000万至3000万人感染HTLV-1。其中5%的人会患上成人T细胞白血病。ATL的预后很差，尽管目前的治疗方法，中位生存时间不到一年。我们的总体目标是找到可以消除对治疗的耐药性的治疗方法，从而最终延长患者的生存时间。

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.