Ewch i’r prif gynnwys

Yr Athro Daniel Aeschlimann

Cyfarwyddwr Ymchwil, Athro Gwyddorau Biolegol

Ysgol Deintyddiaeth

Email:
aeschlimanndp@cardiff.ac.uk
Telephone:
+44 (0)29 2074 4240
Fax:
+44 (0)29 2074 4509
Ar gael fel goruchwyliwr ôl-raddedig

Research Theme

Tissue Engineering & Reparative Dentistry

Research Group

Extracellular Matrix (ECM) in Repair & Remodelling

Research Interests

Structure and function of proteins in the extracellular matrix, mechanisms for the assembly of supramolecular structures and role of extracellular matrix in guiding cellular responses. Molecular aspects of connective tissue in development and ageing. The role of protein cross-linking by transglutaminases in these processes. Application of knowledge to understanding and treatment of human diseases, particularly diseases of the musculoskeletal system. Development of smart materials for cell based therapy to promote wound healing and tissue regeneration.

Selected Projects

Action Medical Research "Role of fibroblast extracellular matrix in regulation of epithelial cells in health and disease"

Fibroblasts deposit a highly organized and tissue-specific extracellular matrix and hence provide a local microenvironment that controls repair processes. For example, fibroblasts have an instructive function in regulation of an overlying epithelium and defects in epithelial regeneration result as a consequence of altered matrix deposition or remodelling. Tissue transglutaminase (TG2)-deficient mice display aberrant wound healing responses and we have shown that TG2 (a multifunctional protein associated with the early phase of wound healing) contributes to fibroblast-mediated extracellular matrix remodeling in several ways (Stephens et al., 2004. J. Cell Sci. 117, 3389-3403). In this project, we will use an in-house  developed co-culture model of fibroblasts and epithelial cells that mimics the re-epithelialisation process observed in skin wound healing to investigate whether TG2-mediated extracellular matrix remodelling plays a role in the crosstalk between the two cell types.

BRET / Ryder Briggs Trust $acirc; The role of transglutaminases in immune mediated neurological diseases$acirc;  :

Gluten sensitivity typically presents as celiac disease, a chronic autoimmune-mediated small intestinal disorder. In susceptible individuals with specific human lymphocyte antigens, consumption of gluten triggers a CD4+ T cell response to gliadin as well as a B cell response to gliadin and self antigens. Tissue transglutaminase (TG2) is the autoantigen recognized in the endomysium of the gut by sera from patients with celiac disease. However, gluten sensitivity can manifest as a spectrum of clinical conditions. For example, neurological disorders occur with a frequency of up to 10% among celiac disease patients, but neurological dysfunction can also be the sole presenting feature of gluten sensitivity. Development of autoimmunity directed towards different members of the transglutaminase family could offer an explanation for the diversity in manifestations of gluten sensitivity. We have identified a novel neuronal transglutaminase isozyme (Grenard et al., 2001. J. Biol. Chem. 276, 33066-33078) and this project investigates whether this enzyme is the target of the immune response in patients with neurological dysfunction.

NATO, $acirc; Modelling of hydrodynamic stresses in hydrogel environment that supports vasculogenesis$acirc;  :

A major challenge for cell transplantation and in vitro engineering of larger tissue equivalents, like organs, is the lack of a functional vasculature to deliver sufficient nutrition and oxygenation. A cascade of morphogenetic processes is required for blood vessel formation which besides the now well characterized signalling events (growth factors and chemokines) also involves gradients of small molecules and mechanotransduction through the extracellular environment. This project aims to provide an understanding of the correlation between interstitial fluid flow parameters and angiogenic responses of endothelial cells seeded into a 3-dimensional hydrogel environment (Bulpitt and Aeschlimann, 1999.J. Biomed. Mater. Res. 47, 152-169) and based on this knowledge, to develop technology that allows for the establishment of a simple vasculature for support of engineered organ equivalents.

Career Profile

1990
MSc (Diploma in Biology II: Biochemistry, Biophysical Chemistry, Cell Biology and Molecular Genetics), Biocenter, University of Basel, Basel, Switzerland.

1993
PhD in Biochemistry (rated Summa Cum Laude), University of Basel, Basel, Switzerland.

1993-1994
Postdoctoral fellow in the group of Dr. Mats Paulsson, M. E. MÃ ller-Institute for Biomechanics, University of Bern, Bern, Switzerland.

1994-1996
Fellowship from the European Molecular Biology Organization, Heidelberg, Germany to work with Dr. Deane F. Mosher, Department of Medicine, University of Wisconsin, Madison, USA.

1996-1999
Senior Scientist and Principal Investigator, Division of Orthopedic Surgery, University of Wisconsin, Madison, USA (received Fellowship for Advanced Researchers from Swiss National Science Foundation in 1996/1997)

1999-2001
Lecturer in Biochemistry, Cardiff University, Cardiff, U.K.

2001-
Professor of Biological Sciences, School of Dentistry, Cardiff University, Cardiff, U.K.

Professional Activities

Reviewer for Journals:

Member of Editorial Board of The Journal of Biological Chemistry (2000-2002)

Ad hoc Reviewer for Journals:
Biochemistry, Biomaterials, Cancer Research, Cell Death and Differentiation, European Journal of Biochemistry, European Journal of Cell Biology, Experimental Cell Research, FEBS Lett., Human Molecular Genetics, Journal of Biological Chemistry, Journal of Bone and Mineral Research, Journal of Cell Science, Journal of Clinical Investigation, Journal of Investigative Dermatology, Journal of Neurochemistry, Journal of Orthopedic Research, Matrix Biology, Nature Cell Biology, Neurochemistry International, Osteoarthritis and Cartilage

Reviewer for Funding Bodies:

Action Medical Research, Arthritis Research Campaign, BBSRC, National Kidney Research Fund, Wellcome Trust and National University of Singapore, Singapore

Presentations

Invited seminar/conference speaker:

$acirc;          3rd Symposium of the International Cartilage Repair Society, Gothenburg, Sweden, 2000

$acirc;          11th International Congress of Histochemistry and Cytochemistry, York, UK, 2000

$acirc;          Smith & Nephew, York, UK, 2000

$acirc;          University   of Rome Tor Vergata, Italy, 2000

$acirc;          University of Caen, France, 2000

$acirc;          11th Conference of the European Tissue Repair Society, Cardiff, UK, 2001

$acirc;          International Congress on Transglutaminases, Protein Crosslinking and Coeliac Disease, Tampere, Finland, 2001

$acirc;          Pierre Fabre, Paris, France, 2001

$acirc;          Unilever, Sharnbrook, UK, 2001

$acirc;          10th international Symposium on Coeliac Disease, Paris, France, 2002

$acirc;          University of Muenster, Muenster, Germany, 2002

$acirc;          University of Manchester, Manchester, UK, 2002

$acirc;          European Science Foundation Workshop on Protein Crosslinking in Neuronal Inclusions, Debrecen, Hungary, 2003

$acirc;            8th International Conference on Amino Acids and Proteins, Rome, Italy, 2003.

$acirc;            University of Cologne, Cologne, Germany, 2003

$acirc;            N-Zyme, Darmstadt, Germany, 2003

$acirc;            EC Cost Action Conference on Textile Quality and Biotechnology, Gran Canaria, Spain 2005

$acirc;            European Polymer Federation meeting, the Vosges, France, 2005

$acirc;            Network for Ichthyosis and related Keratinization Disorders, Muenster, Germany, 2005

$acirc;            University of Malaya, Kuala Lumpur, Malaysia, 2005

$acirc;            National University of Singapore, Singapore 2005

$acirc;            Cancer Cell Biology Group, CIMR, University of Cambridge, Cambridge, 2005

$acirc;            SFB Symposium on molecular basis of structural and functional barriers in the skin, Cologne, Germany, 2006

$acirc;            Zedira, Darmstadt, Germany, 2008

Postgraduate Students

Helen Thomas: $acirc;  Characterisation of a novel transglutaminase gene product, TGY, and determination of its biological role$acirc;  , PhD awarded 2004
(oral presentation prize at 7th International Conference on Transglutaminases and Protein Crosslinking Reactions, Ferrara, Italy, 2002)

Kate Silverthorne: $acirc;  Development of $acirc;  smart$acirc;   biomaterials for tissue repair$acirc;  , PhD awarded 2004
(oral presentation prize at Smith& Nephew Research day, York, 2002)

Sally Rosser Davies: $acirc;  Novel transglutaminases and their regulation $acirc;   a potential route to healthy skin$acirc;  , PhD awarded 2005

Lorna Fiedler: $acirc;  Role of decorin in regulation of angiogenesis$acirc;  , PhD awarded 2007
(oral presentation prize at Cardiff Institute for Tissue Engineering and Repair meeting 2004; poster prize at Cardiff Institute for Tissue Engineering and Repair meeting 2005; oral presentation prize at British Matrix Biology Society meeting, Manchester, 2005; poster prize at British Matrix Biology Society meeting, Newcastle, 2006).

Anna Koutoulaki: $acirc;  Molecular and functional analysis of IL-18 receptor regulation$acirc;  , current
(Unilever poster prize at British Society for Dental Research meeting, Durham, 2007)

Jessica Edwards: $acirc;  Role   of transglutaminase in signalling that regulates epithelial responses in wound healing$acirc;  , current

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Isopeptidase assay for analysis of transglutaminase activity

Assay to perform kinetic measurements of transglutaminase activity in a high throughput format for the analysis of regulators/inhibitors of catalysis. This document is an extended version of the BMG Labtech Application Note 234, which contains additional data on reaction conditions and a detailed discussion of catalysis.

Goruchwyliaeth gyfredol

Shannon Turberville

Research student

Meysydd arbenigol

Proffiliau allanol