Molecular Optical Imaging of Key Targets in the Fibrogenic Pathway in Man

人体纤维形成途径关键靶标的分子光学成像

• 批准号: MR/J014702/1
• 负责人: Christopher Haslett
• 金额: $ 102.81万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FJ014702%2F1
• 关键词: Molecular; Optical; Imaging; Key; Targets

Fibrosis, or scarring, is a process which complicates many diseases of the lung and other organs and for which no effective treatment is available. There are currently no ways to detect the activity of fibrosis in human tissues in life.The ability to specifically monitor fibrosis non-invasively in diseased organs would enable stratification of disease and to personalise treatment as well as facilitate the rapid design and testing of new drugs in patients with 'real disease' without the need for animal experimentation.This project aims to develop 'smart' probes to detect fibrosis in 'real time' in human tissues. This is achieved by the combined application of 'cutting-edge' technology to perform optical imaging microscopy deep in diseased organs to detect the activity of a tiny dose of a coloured compound which has been designed to specifically detect key events in the fibrotic process. This 'microdose' involves no toxicity or radiation exposure. This technology will enable us not only to detect fibrosis and develop new drugs for human disease but will also be applicable to scarring diseases in animals. Thus the proposed studies using tissue from donkeys, which have a very high natural incidence of a form of lung scarring which is virtually identical to the human variety, will not only help our human translational pathway, but will also provide the basis of much-needed treatment for sick animals.

纤维化，或疤痕形成，是一个使肺部和其他器官的许多疾病复杂化的过程，并且没有有效的治疗方法。目前还没有方法来检测人体组织中纤维化的活动性。能够对疾病器官中的纤维化进行专门的非侵入性监测，将使疾病分层和个性化治疗，并有助于在不需要动物实验的情况下快速设计和测试新药。该项目的目标是开发“智能”探针，以“实时”检测人体组织中的纤维化。这是通过综合应用“尖端”技术在病变器官深处进行光学成像显微镜来检测微小剂量的有色化合物的活动来实现的，这种化合物被设计成专门检测纤维化过程中的关键事件。这种“微剂量”不涉及任何毒性或辐射暴露。这项技术将使我们不仅能够检测纤维化并开发治疗人类疾病的新药，而且还将适用于动物身上的疤痕疾病。因此，拟议中的使用驴组织的研究不仅有助于我们的人类翻译途径，而且还将为患病动物提供急需的治疗基础。驴组织具有非常高的自然发病率，一种与人类完全相同的肺疤痕。

项目成果

Optical molecular imaging of lysyl oxidase activity - detection of active fibrogenesis in human lung tissue.

• DOI: 10.1039/c5sc01258a
• 发表时间: 2015-08-01
• 期刊: Chemical science
• 影响因子: 8.4
• 作者: Aslam T;Miele A;Chankeshwara SV;Megia-Fernandez A;Michels C;Akram AR;McDonald N;Hirani N;Haslett C;Bradley M;Dhaliwal K
• 通讯作者: Dhaliwal K

Technical advance: autofluorescence-based sorting: rapid and nonperturbing isolation of ultrapure neutrophils to determine cytokine production.

• DOI: 10.1189/jlb.0113040
• 发表时间: 2013-07
• 期刊: Journal of leukocyte biology
• 影响因子: 5.5
• 作者: Dorward DA;Lucas CD;Alessandri AL;Marwick JA;Rossi F;Dransfield I;Haslett C;Dhaliwal K;Rossi AG
• 通讯作者: Rossi AG

Genetic and pharmacological inhibition of CDK9 drives neutrophil apoptosis to resolve inflammation in zebrafish in vivo.

• DOI: 10.1038/srep36980
• 发表时间: 2016-11-11
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Hoodless LJ;Lucas CD;Duffin R;Denvir MA;Haslett C;Tucker CS;Rossi AG
• 通讯作者: Rossi AG

Constitutive apoptosis in equine peripheral blood neutrophils in vitro.

• DOI: 10.1016/j.tvjl.2014.08.029
• 发表时间: 2014-12
• 期刊: Veterinary journal (London, England : 1997)
• 作者: Brazil TJ;Dixon PM;Haslett C;Murray J;McGorum BC
• 通讯作者: McGorum BC

In-situ imaging of neutrophil activation in the human alveolar space with neutrophil activation probe and pulmonary optical endomicroscopy

使用中性粒细胞激活探针和肺光学内窥镜对人肺泡腔中性粒细胞激活进行原位成像

• DOI: 10.1016/s0140-6736(16)00418-9
• 发表时间: 2016
• 期刊: The Lancet
• 作者: Craven T