Identification of novel therapeutic targets for age-related macular degeneration via a combined tissue engineering and systems biology approach

通过组织工程和系统生物学相结合的方法确定年龄相关性黄斑变性的新治疗靶点

基本信息

  • 批准号:
    9181720
  • 负责人:
  • 金额:
    $ 24.29万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2016
  • 资助国家:
    美国
  • 起止时间:
    2016-08-01 至 2018-07-31
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY Age-related macular degeneration (AMD) is the leading cause of blindness in the developed world, and results from inappropriate angiogenesis in the eye. As a result of this mechanism, anti-angiogenic drugs such as anti- vascular endothelial growth factor (VEGF) agents have become the preferred treatment for late-stage, or `wet', AMD. However, these drugs are accompanied by serious risks as they are injected repeatedly into the eye and over 50% of patients still experience vision loss. Unfortunately, the development of more effective therapies has been hampered by limited insight into the molecular mechanisms that promote angiogenesis in the retina. We hypothesize that the combined changes in the extracellular matrix (ECM) and retinal pigment epithelial (RPE) phenotype control angiogenesis in wet AMD. To test this, we propose to develop a tissue-engineered system that mimics several features of outer retinal anatomy and to then characterize angiogenesis in response to AMD-like changes to these features. This novel 3-D platform will allow us to uniquely address specific questions about retinal biology, yield information about the relative influences of retinal properties in regulating angiogenesis, and ultimately identify and screen new therapies for wet AMD. Aim 1: Create a tissue-engineered retinal environment to characterize the relative influences of AMD- mimicking changes on angiogenesis. We will develop a novel 3-D tissue-engineered system simulating key elements of the retinal anatomy. This system will be used to examine angiogenesis by endothelial cells (ECs) in the context of changes in the retinal microenvironment that mimic changes observed in wet AMD. Aim 2: Using a systems biology analysis, identify alternative targets or stage-specific treatments to regulate angiogenesis in AMD. We will utilize our tissue-engineered model to examine receptor activation on the ECs in response to angiogenic ligands secreted by RPE cells across different stages of angiogenesis. We will then use these experiments to construct a predictive computational model that will enable identification of individual (or combined) soluble factors that most strongly promote angiogenesis at various stages of disease. Via in silico perturbations, we will predict outcomes for inhibiting these factors/receptors, and then test these new inhibition strategies in our in vitro experimental model. The outcomes of this work will be: 1) creation of a sophisticated in vitro platform for characterizing the pathophysiology of wet AMD and relative contributions of microenvironmental factors in this process, 2) identification of novel targets and/or stage-specific treatments for wet AMD.
项目摘要 视网膜相关性黄斑变性(AMD)是发达国家致盲的主要原因, 不适当的血管生成。由于这种机制,抗血管生成药物,如抗- 血管内皮生长因子(VEGF)试剂已经成为晚期,或“湿”, AMD.然而,这些药物伴随着严重的风险,因为它们被反复注射到眼睛里, 超过50%的患者仍然经历视力丧失。不幸的是,更有效的治疗方法的发展 由于对促进视网膜血管生成的分子机制了解有限, 我们假设细胞外基质(ECM)和视网膜色素上皮细胞的联合变化 (RPE)表型控制湿性AMD血管生成。为了验证这一点,我们建议开发一种组织工程 模拟外部视网膜解剖结构的几个特征,然后表征血管生成的系统, 对这些功能的AMD式变化的响应。这个新颖的3D平台将使我们能够独特地解决 关于视网膜生物学的具体问题,产生关于视网膜特性的相对影响的信息, 调节血管生成,并最终确定和筛选湿性AMD的新疗法。 目的1:创建一个组织工程化的视网膜环境,以表征AMD的相对影响, 模仿血管生成的变化。我们将开发一种新型的模拟钥匙的三维组织工程系统 视网膜解剖学的要素。该系统将用于检测内皮细胞(EC)的血管生成 在视网膜微环境变化的背景下,模拟在湿性AMD中观察到的变化。 目标2:使用系统生物学分析,确定替代靶点或阶段特异性治疗, 调节AMD中的血管生成。我们将利用我们的组织工程模型来检查受体激活, EC对RPE细胞分泌的血管生成配体的反应跨越血管生成的不同阶段。我们 然后将使用这些实验来构建一个预测计算模型, 单个(或组合)可溶性因子在疾病的不同阶段最强烈地促进血管生成。 通过计算机干扰,我们将预测抑制这些因子/受体的结果,然后测试这些结果。 新的抑制策略在我们的体外实验模型。 这项工作的成果将是:1)创建一个复杂的体外平台,用于表征 湿性AMD的病理生理学和微环境因素在该过程中的相对作用,2) 鉴定湿性AMD的新靶点和/或阶段特异性治疗。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

KRISTYN S MASTERS其他文献

KRISTYN S MASTERS的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('KRISTYN S MASTERS', 18)}}的其他基金

Development of Complex Culture Systems to Study Valvular Dysfunction
开发复杂的培养系统来研究瓣膜功能障碍
  • 批准号:
    8968385
  • 财政年份:
    2015
  • 资助金额:
    $ 24.29万
  • 项目类别:
Combinatorial analysis of migration stimuli for enhanced wound healing
促进伤口愈合的迁移刺激的组合分析
  • 批准号:
    8183086
  • 财政年份:
    2011
  • 资助金额:
    $ 24.29万
  • 项目类别:
Combinatorial analysis of migration stimuli for enhanced wound healing
促进伤口愈合的迁移刺激的组合分析
  • 批准号:
    8469866
  • 财政年份:
    2011
  • 资助金额:
    $ 24.29万
  • 项目类别:
Combinatorial analysis of migration stimuli for enhanced wound healing
促进伤口愈合的迁移刺激的组合分析
  • 批准号:
    8657060
  • 财政年份:
    2011
  • 资助金额:
    $ 24.29万
  • 项目类别:
Combinatorial analysis of migration stimuli for enhanced wound healing
促进伤口愈合的迁移刺激的组合分析
  • 批准号:
    8324996
  • 财政年份:
    2011
  • 资助金额:
    $ 24.29万
  • 项目类别:
Creating Engineered Models of Valvular Disease to Study Anti-Calcific Therapies
创建瓣膜疾病工程模型以研究抗钙化疗法
  • 批准号:
    7590174
  • 财政年份:
    2009
  • 资助金额:
    $ 24.29万
  • 项目类别:
Creating Engineered Models of Valvular Disease to Study Anti-Calcific Therapies
创建瓣膜疾病工程模型以研究抗钙化疗法
  • 批准号:
    7797694
  • 财政年份:
    2009
  • 资助金额:
    $ 24.29万
  • 项目类别:
Creating Engineered Models of Valvular Disease to Study Anti-Calcific Therapies
创建瓣膜疾病工程模型以研究抗钙化疗法
  • 批准号:
    8235867
  • 财政年份:
    2009
  • 资助金额:
    $ 24.29万
  • 项目类别:
Creating Engineered Models of Valvular Disease to Study Anti-Calcific Therapies
创建瓣膜疾病工程模型以研究抗钙化疗法
  • 批准号:
    8055057
  • 财政年份:
    2009
  • 资助金额:
    $ 24.29万
  • 项目类别:
Creating Engineered Models of Valvular Disease to Study Anti-Calcific Therapies
创建瓣膜疾病工程模型以研究抗钙化疗法
  • 批准号:
    8634811
  • 财政年份:
    2009
  • 资助金额:
    $ 24.29万
  • 项目类别:

相似海外基金

Transcriptional assessment of haematopoietic differentiation to risk-stratify acute lymphoblastic leukaemia
造血分化的转录评估对急性淋巴细胞白血病的风险分层
  • 批准号:
    MR/Y009568/1
  • 财政年份:
    2024
  • 资助金额:
    $ 24.29万
  • 项目类别:
    Fellowship
Combining two unique AI platforms for the discovery of novel genetic therapeutic targets & preclinical validation of synthetic biomolecules to treat Acute myeloid leukaemia (AML).
结合两个独特的人工智能平台来发现新的基因治疗靶点
  • 批准号:
    10090332
  • 财政年份:
    2024
  • 资助金额:
    $ 24.29万
  • 项目类别:
    Collaborative R&D
Acute senescence: a novel host defence counteracting typhoidal Salmonella
急性衰老:对抗伤寒沙门氏菌的新型宿主防御
  • 批准号:
    MR/X02329X/1
  • 财政年份:
    2024
  • 资助金额:
    $ 24.29万
  • 项目类别:
    Fellowship
Cellular Neuroinflammation in Acute Brain Injury
急性脑损伤中的细胞神经炎症
  • 批准号:
    MR/X021882/1
  • 财政年份:
    2024
  • 资助金额:
    $ 24.29万
  • 项目类别:
    Research Grant
STTR Phase I: Non-invasive focused ultrasound treatment to modulate the immune system for acute and chronic kidney rejection
STTR 第一期:非侵入性聚焦超声治疗调节免疫系统以治疗急性和慢性肾排斥
  • 批准号:
    2312694
  • 财政年份:
    2024
  • 资助金额:
    $ 24.29万
  • 项目类别:
    Standard Grant
Combining Mechanistic Modelling with Machine Learning for Diagnosis of Acute Respiratory Distress Syndrome
机械建模与机器学习相结合诊断急性呼吸窘迫综合征
  • 批准号:
    EP/Y003527/1
  • 财政年份:
    2024
  • 资助金额:
    $ 24.29万
  • 项目类别:
    Research Grant
FITEAML: Functional Interrogation of Transposable Elements in Acute Myeloid Leukaemia
FITEAML:急性髓系白血病转座元件的功能研究
  • 批准号:
    EP/Y030338/1
  • 财政年份:
    2024
  • 资助金额:
    $ 24.29万
  • 项目类别:
    Research Grant
KAT2A PROTACs targetting the differentiation of blasts and leukemic stem cells for the treatment of Acute Myeloid Leukaemia
KAT2A PROTAC 靶向原始细胞和白血病干细胞的分化,用于治疗急性髓系白血病
  • 批准号:
    MR/X029557/1
  • 财政年份:
    2024
  • 资助金额:
    $ 24.29万
  • 项目类别:
    Research Grant
ロボット支援肝切除術は真に低侵襲なのか?acute phaseに着目して
机器人辅助肝切除术真的是微创吗?
  • 批准号:
    24K19395
  • 财政年份:
    2024
  • 资助金额:
    $ 24.29万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Acute human gingivitis systems biology
人类急性牙龈炎系统生物学
  • 批准号:
    484000
  • 财政年份:
    2023
  • 资助金额:
    $ 24.29万
  • 项目类别:
    Operating Grants
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了