A5034270727- Skin Protection and Aging
- Protease and Inhibitor Mechanisms
- Spine and Intervertebral Disc Pathology
- Advanced Proteomics Techniques and Applications
- Medical Imaging and Analysis
- Musculoskeletal pain and rehabilitation
- S100 Proteins and Annexins
- Bone and Dental Protein Studies
- Connective tissue disorders research
- Heat shock proteins research
- Exercise and Physiological Responses
- Advanced Glycation End Products research
- Oral microbiology and periodontitis research
- Angiogenesis and VEGF in Cancer
- Circadian rhythm and melatonin
- Caveolin-1 and cellular processes
- Antimicrobial Peptides and Activities
- Antioxidant Activity and Oxidative Stress
- Collagen: Extraction and Characterization
- Mast cells and histamine
- Biotin and Related Studies
- Chronic Kidney Disease and Diabetes
- Liver physiology and pathology
- Radiomics and Machine Learning in Medical Imaging
- Elasticity and Material Modeling
University of Manchester
2016-2025
Wellcome Centre for Cell-Matrix Research
2023-2025
Henry Royce Institute
2019-2024
NIHR Oxford Musculoskeletal Biomedical Research Centre
2023-2024
Manchester Academic Health Science Centre
2018-2021
Matrix Research (United States)
2020
Biological tissues are exposed to X-rays in medical applications (such as diagnosis and radiotherapy) research studies (for example microcomputed X-ray tomography: microCT). Radiotherapy may deliver doses up 50Gy both tumour healthy tissues, resulting undesirable clinical side effects which can compromise quality of life. Whilst cellular responses relatively well-characterised, X-ray-induced structural damage the extracellular matrix (ECM) is poorly understood. This study tests hypotheses...
The intervertebral disc (IVD) has a complex and multiscale extracellular matrix structure which provides unique mechanical properties to withstand physiological loading. Low back pain been linked degeneration of the but reparative treatments are not currently available. Characterising disc's 3D microstructure its response in physiologically relevant loading environment is required improve understanding develop new treatments. In this study, techniques for imaging native IVD, measuring...
Abstract Background Extracellular matrices play a critical role in tissue structure and function aberrant remodelling of these is hallmark many age-related diseases. In skin, loss dermal collagens disorganization elastic fibre components are key features photoageing. Although the application some small matrix-derived peptides to aged skin has been shown beneficially affect vitro cell behaviour and, vivo, molecular architecture clinical appearance, discovery new lacked guiding hypothesis....
In contrast to the dynamic intracellular environment, structural extracellular matrix (ECM) proteins with half-lives measured in decades, are susceptible accumulating damage. Whilst conventional approaches such as histology, immunohistochemistry and mass spectrometry able identify age- disease-related changes protein abundance or distribution, these techniques poorly suited characterising molecular We have previously shown that can detect tissue-specific differences proteolytic...
Both protease- and reactive oxygen species (ROS)-mediated proteolysis are thought to be key effectors of tissue remodeling. We have previously shown that comparison amino acid composition can predict the differential susceptibilities proteins photo-oxidation. However, predicting protein susceptibility endogenous proteases remains challenging. Here, we aim develop bioinformatics tools (i) cleavage site locations (and hence putative susceptibilities) (ii) compare predicted vulnerabilities skin...
Abstract Although dysfunctional protein homeostasis (proteostasis) is a key factor in many age‐related diseases, the untargeted identification of structurally modified proteins remains challenging. Peptide location fingerprinting proteomic analysis technique capable identifying structural modification‐associated differences mass spectrometry (MS) data sets complex biological samples. A new webtool (Manchester Location Fingerprinter), applied to photoaged and intrinsically aged skin...
Many soft tissues, such as the intervertebral disc (IVD), have a hierarchical fibrous composite structure which suffers from regional damage. We hypothesise that these tissue regions distinct, inherent fibre and structural response upon loading. Here we used synchrotron computed tomography (sCT) to resolve collagen bundles (∼5μm width) in 3D throughout an intact native rat lumbar IVD under increasing compressive load. Using samples meant boundaries (such endplate-disc or nucleus-annulus)...
Vascular aging is characterized by vessel stiffening, with increased deposition of extracellular matrix (ECM) proteins including collagens. Oxidative DNA damage occurs in vascular aging, but how it regulates ECM and stiffening unknown. We sought to determine the relationship between oxidative regulatory aging.
Extracellular matrices (ECMs) in the intervertebral disc (IVD), lung and artery are thought to undergo age-dependant accumulation of damage by chronic exposure mechanisms such as reactive oxygen species, proteases glycation. It is unknown whether this species-dependant (via differing lifespans hence cumulative exposures) or it can influence progression age-related diseases atherosclerosis. Peptide location fingerprinting (PLF) a new proteomic analysis method, capable non-targeted...
During ageing, the glomerular and tubular basement membranes (BM) of kidney undergo a progressive decline in function that is underpinned by histological changes, including glomerulosclerosis interstitial fibrosis atrophy. This BM-specific ageing thought to result from damage accumulation long-lived extracellular matrix (ECM) protein structures. Determining which BM proteins are susceptible these structure-associated possible mechanisms downstream consequences, critical understand...
Introduction: Exposure to chronic, low-dose UV irradiation (UVR) can lead premature ageing of the skin. Understanding which proteins are affected by acute UVR and photo-dynamically produced reactive oxygen species (ROS) could help inform strategies delay photoageing. Conventional biochemical analyses be used characterize UVR/ROS-induced damage on a protein-by-protein basis we have previously shown using SDS-PAGE that collagen I plasma fibronectin respectively resistant susceptible...
In ageing tissues, long-lived extracellular matrix (ECM) proteins are susceptible to the accumulation of structural damage due diverse mechanisms including glycation, oxidation and protease cleavage. Peptide location fingerprinting (PLF) is a new mass spectrometry (MS) analysis technique capable identifying exhibiting differences in complex proteomes. PLF applied published young aged intervertebral disc (IVD) MS datasets (posterior, lateral anterior regions annulus fibrosus) identified 268...
Abstract Introduction and aims Proteomic analysis of the extracellular matrix (ECM) presents challenges because highly crosslinked low-solubility nature ECM proteins. Traditional homogenization protein digestion approaches result in loss crucial information regarding localization spatial relationships. To address this, spatially resolved proteomics emerges as a powerful tool for exploring heterogeneity within bulk tissues. This study to determine minimum tissue volume required comprehensive...
Abstract Identification of pathways preventing recovery from acute respiratory viral infection is under-studied but essential for long-term health. Using unbiased proteomics, we reveal an unexpected persistent reduction in lung basement membrane proteins mice recovered influenza infection. Basement provides a critical scaffold heterogeneous cell types and the they secrete/express at endothelial epithelial barrier. Further peptide location fingerprinting analysis shows inherent...
Abstract Although dysfunctional protein homeostasis (proteostasis) is a key factor in many age-related diseases, the untargeted identification of structural modifications proteins remains challenging. Peptide location fingerprinting proteomic analysis technique capable identifying modification-associated differences mass spectrometry (MS) datasets complex biological samples. A new webtool (Manchester Location Fingerprinter), applied to photoaged and intrinsically aged skin proteomes, can...
In ageing tissues, long-lived extracellular matrix (ECM) proteins are susceptible to the accumulation of structural damage due diverse mechanisms including glycation, oxidation and protease cleavage. Peptide location fingerprinting (PLF) is a new mass spectrometry (MS) analysis technique capable identifying exhibiting differences in complex proteomes. PLF applied published young aged intervertebral disc (IVD) MS datasets (posterior, lateral anterior regions annulus fibrosus), identified 268...
Chronic UVR exposure of human skin can result in photo-ageing which manifests both externally and internally (as remodelling layers including the extracellular matrix-rich dermis). However, intermittent nature over a timescale decades combined with longevity many structural dermal proteins makes identification targets mechanisms challenging. Over past ten years work our group has demonstrated that: (i) are rich amino acid chromophores susceptible to physiologically relevant doses solar...