A New Disease Platform Leveraging Complex Drosophila and Mammalian Models

利用复杂果蝇和哺乳动物模型的新疾病平台

基本信息

批准号：
9118383
负责人：
Ross Leigh Cagan
金额：
$ 198.78万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-08-01 至 2020-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9118383
关键词：
Acute Address Adverse effects Affect Animals Applied Research BAY 54-9085 Cardiac Myocytes Cell model Cells Chronic Colorectal Cancer Communities Complex Data Databases Disease Disease model Disease remission Docking Drosophila genus Drug Targeting Emerging Technologies Equilibrium FDA approved Generations Genetic Genetic Screening Genomics Goals Hereditary Disease Homeostasis Human Hypertrophic Cardiomyopathy Implant Lead Libraries Malignant Neoplasms Mendelian disorder Modeling Mus Mutation Normal tissue morphology Patients Pharmaceutical Chemistry Pharmaceutical Preparations Pharmacotherapy Phenotype Procedures Process Rare Diseases Research Series Stem cells Structure Synapses Technology Testing Therapeutic Therapeutic Index Thinking Tissues Transgenic Model Transgenic Organisms Validation Variant Xenograft Model animal efficacy base computational chemistry cost cost effective design drug discovery fly human stem cells improved induced pluripotent stem cell novel novel strategies personalized medicine personalized therapeutic public health relevance response screening therapeutic target therapy development tool tumor tumor xenograft

项目摘要

DESCRIPTION (provided by applicant): The goal of disease research is to develop therapeutics. While many diseases have been successfully addressed, genetics-based diseases have proven more difficult to develop therapies that bring the disease into remission without significant side effects. Doing so requires addressing both disease complexity and also the complex interactions within the whole body network that affect disease as well as response to therapies. The central theme of this Proposal is to leverage the advantages of the fruit fly Drosophila to build a `functional network platform' designed to identify therapeutics that address disease complexity. We then use stem cell approaches to explore the most promising leads in a human cell context. At each step we make a concerted effort to embrace complexity both in our models and our lead therapeutics. The overall objective of this Proposal is to further develop a platform and pipeline that can be adapted to a broad range of diseases. In the attached Projects, we describe our emerging technologies designed to weave together complementary disease models into a seamless platform designed to build drugs and personalized therapeutics rapidly and at a reasonable cost. We select two diseases-colorectal cancer and RASopathy- to develop and demonstrate the strength of our platform to address both a rare Mendelian disease and one of the most common cancers. The former example tests whether our platform can provide a rapid and cost-effective approach to orphan diseases that require sophisticated therapeutics suitable for long-term treatment. The latter provides an example of how it can embrace disease complexity to build new generation lead therapeutics for a disease that remains a key unmet need in our community. Once developed, we will offer a readily accessible standard operating procedure that will most efficiently bring our platform to the applied science community.

描述（由申请人提供）：疾病研究的目标是开发治疗方法，但事实证明，基于遗传的疾病更难开发出在没有明显副作用的情况下缓解疾病的治疗方法。解决疾病的复杂性以及影响疾病和治疗反应的全身网络内的复杂相互作用。该提案的中心主题是利用果蝇的优势来构建一个“功能网络平台”。确认然后，我们使用干细胞方法来探索人类细胞环境中最有希望的线索。该提案的总体目标是在每一步中共同努力，以适应我们的模型和治疗方法的复杂性。进一步开发可适应广泛疾病的平台和管道在随附的项目中，我们描述了我们的新兴技术，旨在将互补的疾病模型编织成一个无缝平台，旨在快速、快速地构建药物和个性化疗法。我们选择两个合理的成本。结直肠癌和 RAS 病 - 开发并展示我们的平台在解决罕见孟德尔疾病和最常见癌症之一方面的实力。前一个示例测试了我们的平台是否可以提供一种快速且经济高效的治疗孤儿疾病的方法。这提供了一个例子，说明如何应对疾病的复杂性，为我们社区尚未满足的关键需求建立新一代的领先疗法。易于使用的标准操作程序将最有效地将我们的平台引入应用科学界。