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：
9306960
负责人：
Ross Leigh Cagan
金额：
$ 188.87万
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/9306960
关键词：
Acute Address Adverse effects Affect Alpha Cell 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 FDA approved Generations Genetic Genetic Screening Genomics Goals Hereditary Disease Homeostasis Human Hypertrophic Cardiomyopathy Implant Industrialization 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 Tumor Initiators 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 stem-like cell 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（由适用提供）：疾病研究的目的是开发治疗。尽管已经成功解决了许多疾病，但事实证明，基于遗传学的疾病难以开发使该疾病缓解而没有显着副作用的疗法。这样做需要解决影响疾病以及对疗法反应的整个身体网络中的复杂相互作用。该提案的核心主题是利用果蝇果蝇的优势建立一个“功能网络平台”，旨在识别解决疾病复杂性的治疗。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铅。在每个步骤中，我们都齐心协力地努力在模型和铅疗法中都采用复杂性。该提案的总体目的是进一步开发可以适应广泛疾病的平台和管道。在所附项目中，我们描述了我们的新兴技术，旨在将互补疾病模型共同编织到一个无缝的平台中，旨在以合理的成本快速建立药物和个性化治疗。我们选择两种疾病 - 色直肠癌和rasopathy-来发展和证明我们平台的强度，以解决一种罕见的孟德尔氏病和最常见的癌症之一。前一个示例测试我们的平台是否可以为需要适合长期治疗的复杂疗法提供快速且具有成本效益的孤儿疾病。后者提供了一个例子，说明了它如何包含疾病复杂性，以建立新一代铅疗法，以使我们的社区中仍然是未满足的疾病。一旦开发，我们将提供一项易于访问的标准操作程序，最有效地将我们的平台带到了应用科学界。