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School of Dentistry

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Research in Tissue Injury & Repair

Professor Tony Smith
Professor Iain Chapple,
Professor Damien Walmsley
Professor Philip Lumley
Dr Jacques Nor
Professor Helen Griffiths
Dr Paul Cooper
Dr John Matthews
Professor Gabriel Landini
Dr Simon Lea
Dr Ben Scheven
Mr Mike Milward
Mr Philip Tomson

image Confocal microscopic demonstration of neutrophils before (left) and after (right) NETosis (release of extracellular DNA traps)
Click to magnify


Understanding the cellular and molecular processes underlying tissue injury and health is a tenet of this theme area to drive a focussed approach for novel developments in disease diagnosis, prevention and therapy via reparative and regenerative mechanisms.  This reinforces a central strategy in the School’s research of providing a robust scientific basis to inform the translation of the research into clinical practice. 

image This approach is highlighted in our Pulp Biology and Endodontics programme of research where understanding relationships between tissue injury events during disease and regenerative processes has been important in identifying how opportunities for regeneration may be best exploited and how inflammatory response mediators may impact on it (Smith, Cooper, Scheven, Lumley, Tomson).


image Our pioneering research on dental regeneration has two central themes – the stem / progenitor cells involved in the regenerative events and the matrix-mediated cellular signalling processes. Selection and isolation of stem cells with dentinogenic potentiality (Smith, Cooper) now provides us with a valuable approach to clinical translation of this research for new regenerative therapies, which will be further facilitated through our development of a novel growth factor-hydrogel capable of inducing de novo dentinogenesis (Smith).

image The mechanistic basis for use of calcium hydroxide in pulp capping regenerative therapies has long been unclear, but our pivotal demonstration of solubilisation of matrix-bound growth factors and modulation of pulp gene expression by calcium hydroxide now provides clarification of this (Smith, Cooper). This has also led to mechanistic studies on the action of Mineral Trioxide Aggregate (MTA) (Tomson, Cooper, Lumley, Smith) and the team is making strong contributions at the cutting-edge of regenerative endodontic research.

Our collaboration with Nor (Michigan) has been strengthened by his appointment as an Honorary Professor, which is enhancing our programme of research on pulp regeneration and engineering and also, vascular biology within both the pulp (Smith) and oral cancer (Landini) areas.

image The recent appointment of an experienced cell biologist with a background in the biotechnology industry (Scheven) has allowed the pulp regeneration programme of research to branch out and examine the biological effects of ultrasound (Scheven, Cooper, Shelton, Walmsley, Smith), which has considerable potential as a tool to modulate regenerative processes. These studies complement and extend the programme of ultrasound research led by Walmsley and Lea with strong EPSRC and industrial support, in which the focus has been on assessment of the design of ultrasound instrumentation and wear of instrument tips, together with research on use of inertial cavitation for tissue preparation during restoration. Strong, EPSRC funded, interdisciplinary links with Schools of Engineering at Cardiff University and Chemistry at Bath University highlight the international competitiveness of this research.

Click Here to view our Ultrasound Web Pages

image A major focus of the periodontal research group lies in unravelling some of the complex stress response pathways in periodontitis, at the molecular, cellular and clinical level. Broad expertise has allowed the study of interactions between oral bacteria, epithelial cells and those of the inflammatory-immune system. Publications and research awards have led the group to becoming internationally leading in the area of redox biology mechanisms underpinning the pathogenesis of periodontitis (Chapple, Matthews) and in the development of novel host-modulating therapies. This work is complemented by the appointment of a leading redox biology researcher,(Griffiths, Aston) as an Honorary Professor.

MRC-funded studies of peripheral blood neutrophil hyper-inflammation mediated via reactive oxygen species, have unravelled for the first time, a functional and reversible peripheral blood neutrophilic hyper-reactivity as well as a constitutional hyper-activity (Matthews, Chapple), which appears to underlie compromised plasma and crevicular fluid total and specific antioxidant defences (Chapple, Matthews).

A landmark study demonstrated a key role for reduced glutathione in inflammatory periodontitis and subsequent work has demonstrated its fundamental role in controlling epithelial cytokine  and chemokine production at the genomic and transcriptomic level (Cooper, Milward, Matthews, Chapple). This has led to further leading research into the applied biology of interferon-neutrophil and bacterial DNA-neutrophil interactions and the group have been the first outside the USA to demonstrate production of neutrophil extracellular traps (NETS) (Cooper, Chapple, Roberts, Matthews). 

The unique studies in microbial endocrinology (Roberts, Chapple, Matthews) and the elucidation of autoinducer and siderophore-like stress responses of oral bacteria have demonstrated how periodontal bacteria can take advantage of a stressed host. The role of such pathogens in neutrophil NET formation is forging new avenues of enquiry. A series of studies have shed light upon the role of PDGF and the TGF-β family of growth factors in the pathogenesis of drug-induced and hereditary gingival fibromatosis (Matthews, Chapple). The recent appointment of Dietrich to the chair in Oral Surgery significantly enhances our activities in the periodontal research area and will also, provide strong epidemiological contributions to the Primary Dental Care theme area in the future.

image Our innovative research on imaging and the computational modelling of patho-physiological processes (Landini) has led to a number of important cross-disciplinary international collaborations with significant contributions to the development of evidence-based diagnosis and intelligent instrumentation in pathological science and has attracted EPSRC funding. Characterisation of oral cancer invasion patterns using fractal geometry, epithelial architecture using graph theory and studies on organ mosaic patterns and neuronal complexity are all providing exciting prospects (Landini). Computational modelling of organogenesis and tissue morphogenesis has provided a valuable new tool for study of these processes, which is also being exploited for study of mechanisms of radicular cyst growth (Landini). 

 

Join the Research Teams at Birmingham
We are happy to consider EU and international scientists wishing to join our research force at the School of Dentistry through the of Marie Curie EIF or IIF programmes (funded for up to two years). Please contact us to discuss the possibilities available.