Professor Daniel Aeschlimann

Professor of Biological Sciences

School of Dentistry

: Available for postgraduate supervision

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:

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; 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.

2024

Floare, M., Wharton, S. B., Simpson, J. E., Aeschlimann, D., Hoggard, N. and Hadjivassiliou, M. 2024. Cerebellar degeneration in Gluten ataxia is linked to microglial activation. Brain Communications 6(2), article number: fcae078. (10.1093/braincomms/fcae078)
Bauer, L., Edwards, J., Heil, A., Dewitt, S., Biebermann, H., Aeschlimann, D. and Knauper, V. 2024. Mesenchymal transglutaminase 2 activates epithelial ADAM17: link to G-protein coupled receptor 56 (ADGRG1) signalling. International Journal of Molecular Sciences 25(4), article number: 2329. (10.3390/ijms25042329)

2022

Ganesh, R. A. et al. 2022. Multi-omics analysis of glioblastoma and glioblastoma cell line: Molecular insights into the functional role of GPR56 in mesenchymal transition. Frontiers in Oncology 12, article number: 841890. (10.3389/fonc.2022.841890)
Büchold, C. et al. 2022. Features of ZED1227: The first-in-class tissue transglutaminase inhibitor undergoing clinical evaluation for the treatment of celiac disease. Cells 11(10), article number: 1667. (10.3390/cells11101667)

2021

Schulze-Krebs, A. et al. 2021. Transglutaminase 6 is colocalized and interacts with mutant Huntingtin in Huntington disease rodent animal models. International Journal of Molecular Sciences 22(16), article number: 8914. (10.3390/ijms22168914)

2020

Hadjivassiliou, M., Reunala, T., Hervonen, K., Aeschlimann, P. and Aeschlimann, D. 2020. TG6 auto-antibodies in dermatitis herpetiformis. Nutrients 12(9), article number: 2884. (10.3390/nu12092884)

2019

Hadjivassiliou, M. et al. 2019. Neurological deficits in patients with newly diagnosed coeliac disease are frequent and linked to TG6 autoimmunity. Clinical Gastroenterology and Hepatology 17(13), pp. 2678-2686.e2. (10.1016/j.cgh.2019.03.014)

2018

Shanmugarajah, P. D. et al. 2018. Phenytoin-related ataxia in patients with epilepsy: clinical and radiological characteristics. Seizure - European Journal of Epilepsy 56, pp. 26-30. (10.1016/j.seizure.2018.01.019)
De Leo, L. et al. 2018. Anti-transglutaminase 6 autoantibody development in children with celiac disease correlates with duration of gluten exposure. Journal of Pediatric Gastroenterology and Nutrition 66(1), pp. 64-68. (10.1097/MPG.0000000000001642)

2017

Zis, P. et al. 2017. Transglutaminase 6 antibodies in gluten neuropathy. Digestive and Liver Disease 49(11), pp. 1196-1200. (10.1016/j.dld.2017.08.019)
Tripathy, D. et al. 2017. Mutations in TGM6 induce the unfolded protein response in SCA35. Human Molecular Genetics 26(19), pp. 3749-3762. (10.1093/hmg/ddx259)
Aeschlimann, D. and Knauper, V. 2017. P2X7 receptor-mediated TG2 externalization: a link to inflammatory arthritis?. Amino Acids 49(3), pp. 453-460. (10.1007/s00726-016-2319-8)

2016

Shanmugarajah, P. D. et al. 2016. Alcohol-related cerebellar degeneration: not all down to toxicity?. Cerebellum & Ataxias 3, article number: 17. (10.1186/s40673-016-0055-1)
Hadjivassiliou, M. et al. 2016. Neurological dysfunction in coeliac disease and non-coeliac gluten sensitivity. American Journal of Gastroenterology 111(4), pp. 561-567. (10.1038/ajg.2015.434)
Mitoma, H. et al. 2016. Consensus Paper: Neuroimmune mechanisms of cerebellar ataxias. Cerebellum 15(2), pp. 213-232. (10.1007/s12311-015-0664-x)
Bloom, A. C. et al. 2016. Deletion of the membrane complement inhibitor CD59a drives age and gender-dependent alterations to bone phenotype in mice. Bone 84, pp. 253-261. (10.1016/j.bone.2015.12.014)
Hadjivassiliou, M., Sanders, D. S. and Aeschlimann, D. 2016. The neuroimmunology of gluten intolerance. In: Constantinescu, C., Arsenescu, R. and Arsenescu, V. eds. Neuro-Immuno-Gastroenterology. Springer International, pp. 1-23., (10.1007/978-3-319-28609-9)

2015

Adamczyk, M., Griffiths, R., Dewitt, S., Knauper, V. and Aeschlimann, D. 2015. P2X7 receptor activation regulates rapid unconventional export of transglutaminase-2. Journal of Cell Science 128(24), pp. 4615-4628. (10.1242/jcs.175968)
Hadjivassiliou, M., Sanders, D. D. and Aeschlimann, D. P. 2015. Gluten related disorders: Gluten atxia. Digestive Diseases 33(2), pp. 264-268., article number: 369509. (10.1159/000369509)
Aeschlimann, D. and Hadjivassiliou, M. 2015. Spotlight: Transglutaminase antibodies in ataxia. Zedira Transglutaminase Speciality Reagents Catalogue 2015, pp. 43-43.

2014

Sarrigiannis, P. G., Hoggard, N., Aeschlimann, D., Sanders, D. S., Grünewald, R. A., Unwin, Z. C. and Hadjivassiliou, M. 2014. Myoclonus ataxia and refractory coeliac disease. Cerebellum & Atxias 1(11) (10.1186/2053-8871-1-11)
Stenberg, R., Hadjivassiliou, M., Aeschlimann, P., Hoggard, N. and Aeschlimann, D. 2014. Anti-transglutaminase 6 antibodies in children and young adults with cerebral palsy. Autoimmune Diseases 2014, pp. 1-8., article number: 237107. (10.1155/2014/237107)

2013

Adamczyk, M., Heil, A. and Aeschlimann, D. 2013. Real-time fluorescence assay for monitoring transglutaminase activity. Application Notes from BMG Labtech, article number: 234.
Hadjivassiliou, M. et al. 2013. Transglutaminase 6 antibodies in the diagnosis of gluten ataxia. Neurology 80(19), pp. 1740- 1745. (10.1212/WNL.0b013e3182919070)
Thomas, H. et al. 2013. Transglutaminase 6: A protein associated with central nervous system development and motor function. Amino Acids 44(1), pp. 161-177. (10.1007/s00726-011-1091-z)
Johnson, A. M., Dale, R. C., Wienholt, L., Hadjivassiliou, M., Aeschlimann, D. and Lawson, J. A. 2013. Coeliac disease, epilepsy, and cerebral calcifications: Association with TG6 autoantibodies. Developmental Medicine & Child Neurology 55(1), pp. 90-93. (10.1111/j.1469-8749.2012.04369.x)

2011

Aeschlimann, D. and Hadjivassiliou, M. 2011. Transglutaminase 6 as a diagnostic indicator of autoimmune diseases. EP 1 978 364 B1 [Patent].
Bloom, A. C., Collins, F., Evans, B. A. J., Aeschlimann, D. P., Morgan, B. P. and Williams, A. S. 2011. CD59 an unexpected protective role in bone [Abstract]. Bone 48, pp. S161-S162.
Yan, J. Y. et al. 2011. Decorin GAG synthesis and TGF-beta signaling mediate Ox-LDL-induced mineralization of human vascular smooth muscle cells. Arteriosclerosis Thrombosis and Vascular Biology 31(3), pp. 608-615. (10.1161/atvbaha.110.220749)
Hadjivassiliou, M., Aeschlimann, D., Grunewald, R. A., Sanders, D. S., Sharrack, B. and Woodroofe, N. 2011. GAD antibody-associated neurological illness and its relationship to gluten sensitivity. Acta Neurologica Scandinavica 123(3), pp. 175-180. (10.1111/j.1600-0404.2010.01356.x)

2010

Stamnaes, J., Dorum, S., Fleckenstein, B., Aeschlimann, D. and Sollid, L. M. 2010. Gluten T cell epitope targeting by TG3 and TG6; implications for dermatitis herpetiformis and gluten ataxia. Amino Acids 39(5), pp. 1183-1191. (10.1007/s00726-010-0554-y)
Boscolo, S. et al. 2010. Anti transglutaminase antibodies cause ataxia in mice. PLoS ONE 5(3), article number: e9698. (10.1371/journal.pone.0009698)
Koutoulaki, A., Langley, M. S., Sloan, A. J., Aeschlimann, D. and Wei, X. 2010. TNF alpha and TGF-beta 1 influence IL-18-induced IFN gamma production through regulation of IL-18 receptor and T-bet expression. Cytokine 49(2), pp. 177-184. (10.1016/j.cyto.2009.09.015)
Hadjivassiliou, M. and Aeschlimann, D. P. 2010. Gluten sensitivity and the CNS: diagnosis and treatment - Authors' reply. The Lancet Neurology 9(7), pp. 654-655. (10.1016/S1474-4422(10)70150-2)
Sugai, E. et al. 2010. New Serology Assays Can Detect Gluten Sensitivity among Enteropathy Patients Seronegative for Anti-Tissue Transglutaminase. Clinical Chemistry 56(4), pp. 661-665. (10.1373/clinchem.2009.129668)
Hadjivassiliou, M., Sanders, D. S., Grunewald, R. A., Woodroofe, N., Boscolo, S. and Aeschlimann, D. P. 2010. Gluten sensitivity: from gut to brain. Lancet Neurology 9(3), pp. 318-330. (10.1016/S1474-4422(09)70290-X)

2009

Toth, B. et al. 2009. Transglutaminase 2 is needed for the formation of an efficient phagocyte portal in macrophages engulfing apoptotic cells. Journal of Immunology 182(4), pp. 2084-2092. (10.4049/jimmunol.0803444)
Yan, J. Y., Menys, V., Gotting, C., Muller, B., Aeschlimann, D. and Alexander, M. Y. 2009. Glycosaminoglycan chain synthesis on decorin contributes to oxidative stress-induced calcification of human vascular smooth muscle cells. Heart 95(22) (10.1136/hrt.2009.181669k)
Hadjivassiliou, M., Aeschlimann, P. C. and Aeschlimann, D. 2009. TG6 ATAXIA. Journal of Neurology Neurosurgery and Psychiatry 80(11) (10.1136/jnnp.2009.191759q)

2008

Chen, L., Wei, X., Evans, B. A. J., Jiang, W. G. and Aeschlimann, D. 2008. IL-23 promotes osteoclast formation by up-regulation of receptor activator of NF-kappa B (RANK) expression in myeloid precursor cells. European Journal of Immunology 38(10), pp. 2845-2854. (10.1002/eji.200838192)
Hadjivassiliou, M., Aeschlimann, P. C., Strigun, A., Sanders, D. S., Woodroofe, N. and Aeschlimann, D. 2008. Autoantibodies in gluten ataxia recognize a novel neuronal transglutaminase. Annals of Neurology 64(3), pp. 332-343. (10.1002/ana.21450)
Fiedler, L., Schonherr, E. H., Waddington, R. J., Niland, S., Seidler, D. G., Aeschlimann, D. and Eble, J. A. 2008. Decorin regulates endothelial cell motility on collagen I through activation of insulin-like growth factor I receptor and modulation of α2β1 integrin activity. Journal of Biological Chemistry 283(25), pp. 17406-17415. (10.1074/jbc.M710025200)

2007

Zhurov, A., Limbert, G. R. J., Aeschlimann, D. and Middleton, J. 2007. A constitutive model for the periodontal ligament as a compressible transversely isotropic viscohyperelastic tissue. Computer methods in biomechanics and biomedical engineering 10(3), pp. 223-235. (10.1080/13639080701314894)
Aeschlimann, D. and Bulpitt, P. 2007. Functionalized derivatives of hyaluronic acid, formation of hydrogels in situ using same, and methods for making and using same. US patent 7, 196,180 [Patent].
Kazenin, D. A., Karlov, S. P., Pokusaev, B. G., Zhurov, A. I. and Aeschlimann, D. 2007. The calculation of geometric and operating parameters of a flow microbioreactor for cultivation of stem cells. Vestnik of Samara State University, Mechanics 4, pp. 169-175.
Lammie, D., Osborne, J., Aeschlimann, D. and Wess, T. J. 2007. Rapid shape determination of tissue transglutaminase using high-throughput computing. Acta Crystallographica Section D: Biological Crystallography 63(9), pp. 1022-1024. (10.1107/S0907444907032933)

2006

Aeschlimann, D. and Grenard, P. M. 2006. Transglutaminase gene products. US patent 7,052,890 [Patent].

2004

Stephens, P. et al. 2004. Crosslinking and G-protein functions of transglutaminase 2 contribute differentially to fibroblast wound healing responses. Journal of cell science 117(15), pp. 3389-3403. (10.1242/jcs.01188)
Aeschlimann, D. and Evans, B. A. J. 2004. The vital osteoclast: how is it regulated? [Editorial]. Cell Death and Differentiation 11(S), pp. S5-S7. (10.1038/sj.cdd.4401470)
Paulsson, M., Sardy, M., Odenthal, U., Karpati, S., Smyth, N. and Aeschlimann, D. 2004. Diagnosis of gluten sensitive enteropathy and other autoimmunopathies. European Patent 1,200,827 [Patent].

2003

Szondy, Z. et al. 2003. Transglutaminase 2-/- mice reveal a phagocytosis-associated crosstalk between macrophages and apoptotic cells. Proceedings of the National Academy of Sciences 100(13), pp. 7812-7817. (10.1073/pnas.0832466100)
Aeschlimann, D. and Thomas, H. 2003. "Brain" transglutaminase: molecular diversity and function. Presented at: Protein Cross-Linking in Neuronal Inclusions, Debrecen, HungaryProceedings of the workshop on protein cross-linking in neuronal inclusions, Debrecen, Hungary. pp. 111-116.
Aeschlimann, D. and Bulpitt, P. 2003. Functionalized derivatives of hyaluronic acid, formation of hydrogels in situ using same, and methods for making and using same. US patent 6,630,457 [Patent].

2001

Aeschlimann, D. 2001. Transglutaminase: Protein cross-linking enzymes in tissues and body fluids. Presented at: Transglutaminases, Protein-Cross-Linking and Coeliac Disease workshop, Tampere, Finland, 14-15 September 2001Proceedings of the workshop on transglutaminases, protein-cross-linking and coeliac disease, Tampere, Finland. pp. 15-22.
Wagener, R., Kobbe, B., Aszodi, A., Aeschlimann, D. and Paulsson, M. 2001. Characterization of the mouse matrilin-4 gene: a 5' antiparallel overlap with the gene encoding the transcription factor RBP-L. Genomics 76(1-3), pp. 89-98. (10.1006/geno.2001.6589)
Grenard, P. M., Bates, M. K. and Aeschlimann, D. 2001. Evolution of transglutaminase genes: identification of a transglutaminase gene cluster on human chromosome 15q15. Structure of the genes encoding transglutaminase X and a novel gene family member, Transglutaminase Z. Journal of biological chemistry 276(35), pp. 33066-33078. (10.1074/jbc.M102553200)
Best, T. M., Shehadeh, S. E., Leverson, G., Michel, J. T., Corr, D. T. and Aeschlimann, D. 2001. Analysis of changes in mRNA levels of myoblast- and fibroblast-derived gene products in healing skeletal muscle using quantitative reverse transcription-polymerase chain reaction. Journal of Orthopaedic Research 19(4), pp. 565-572. (10.1016/S0736-0266(00)00067-X)

2000

Aeschlimann, D. and Thomazy, V. 2000. Protein crosslinking in assembly and remodelling of extracellular matrices: the role of transglutaminases. Connective Tissue Research 41(1), pp. 1-27. (10.3109/03008200009005638)

1999

Aeschlimann, D. P. and Mosher, D. F. 1999. Transglutaminase and gene encoding same. AU9037398A [Patent].
Raghunath, M., Cankay, R., Kubitscheck, U., Fauteck, J. D., Mayne, R., Aeschlimann, D. and Schlötzer-Schrehardt, U. 1999. Transglutaminase activity in the eye: cross-linking in epithelia and connective tissue structures. Investigative Ophthalmology & Visual Science 40(12), pp. 2780-2787.
Gaudry, C. A., Verderio, E., Aeschlimann, D., Cox, A., Smith, C. and Griffin, M. 1999. Cell surface localization of tissue transglutaminase is dependent on a fibronectin-binding site in its N-terminal beta-sandwich domain. The Journal of Biological Chemistry 274(43), pp. 30707-30714. (10.1074/jbc.274.43.30707)
Bulpitt, P. and Aeschlimann, D. 1999. New strategy for chemical modification of hyaluronic acid: preparation of functionalized derivatives and their use in the formation of novel biocompatible hydrogels. Journal of Biomedical Materials Research 47(2), pp. 152-169. (10.1002/(SICI)1097-4636(199911)47:2<152::AID-JBM5>3.0.CO;2-I)
Lindblom, A. et al. 1999. The Intrinsic Factor-Vitamin B12 Receptor, Cubilin, Is Assembled into Trimers via a Coiled-coil α-Helix. Journal of Biological Chemistry 274(10), pp. 6374-6380.

1998

Juergensen, K., Aeschlimann, D. and Hunziker, E. B. 1998. Method of promoting adhesion between tissue surfaces. US patent 5,736,132 [Patent].
Aeschlimann, D., Koeller, M. K., Allen-Hoffmann, B. L. and Mosher, D. F. 1998. Isolation of a cDNA encoding a novel member of the transglutaminase gene family from human keratinocytes. Detection and identification of transglutaminase gene products based on reverse transcription-polymerase chain reaction with degenerate primers. The Journal of Biological Chemistry 273(6), pp. 3452-3460. (10.1074/jbc.273.6.3452)
Hohl, D., Aeschlimann, D. and Huber, M. 1998. In vitro and rapid in situ transglutaminase assays for congenital ichthyoses - a comparative study. Journal of Investigative Dermatology 110(3), pp. 268-271. (10.1046/j.1523-1747.1998.00132.x)
Tooney, P. A., Sakai, T., Sakai, K., Aeschlimann, D. and Mosher, D. F. 1998. Restricted localization of thrombospondin-2 protein during mouse embryogenesis: a comparison to thrombospondin-1. Matrix Biology 17(2), pp. 131-143. (10.1016/S0945-053X(98)90026-9)

1997

Schittny, J. C., Paulsson, M., Vallan, C., Burri, P. H., Kedei, N. and Aeschlimann, D. 1997. Protein cross-linking mediated by tissue transglutaminase correlates with the maturation of extracellular matrices during lung development. American Journal of Respiratory Cell and Molecular Biology 17(3), pp. 334-343.
Bürgi-Saville, M. E. et al. 1997. Expression patterns of extracellular matrix components in native and cultured normal human thyroid tissue and in human toxic adenoma tissue. Thyroid: official journal of the American Thyroid Association 7(3), pp. 347-356. (10.1089/thy.1997.7.347)
Jürgensen, K., Aeschlimann, D., Cavin, V., Genge, M. and Hunziker, E. B. 1997. A new biological glue for cartilage-cartilage interfaces: tissue transglutaminase. The Journal of Bone and Joint Surgery (American Volume) 79(2), pp. 185-193.

1996

Nemes, Z., Friis, R. R., Aeschlimann, D., Saurer, S., Paulsson, M. and Fésüs, L. 1996. Expression and activation of tissue transglutaminase in apoptotic cells of involuting rodent mammary tissue. European Journal of Cell Biology 70(2), pp. 125-133.
Juergensen, K., Aeschlimann, D. and Hunziker, E. B. 1996. Biological adhesive composition and method of promoting adhesion between tissue surfaces. US patent 5,549,904 [Patent].
Aeschlimann, D., Mosher, D. and Paulsson, M. 1996. Tissue transglutaminase and factor XIII in cartilage and bone remodeling. Seminars in Thrombosis and Hemostasis 22(5), pp. 437-443. (10.1055/s-2007-999043)
Chen, H., Aeschlimann, D., Nowlen, J. and Mosher, D. F. 1996. Expression and initial characterization of recombinant mouse thrombospondin 1 and thrombospondin 3. FEBS Letters 387(1), pp. 36-41. (10.1016/0014-5793(96)00460-7)
Raghunath, M. et al. 1996. Cross-linking of the dermo-epidermal junction of skin regenerating from keratinocyte autografts. Anchoring fibrils are a target for tissue transglutaminase. The Journal of Clinical Investigation 98(5), pp. 1174-1184. (10.1172/JCI118901)

1995

Kleman, J. P., Aeschlimann, D., Paulsson, M. and van der Rest, M. 1995. Transglutaminase-catalyzed cross-linking of fibrils of collagen V/XI in A204 rhabdomyosarcoma cells.. Biochemistry 34(42), pp. 13768-13775.
Hohenadl, C., Mann, K., Mayer, U., Timpl, R., Paulsson, M. and Aeschlimann, D. 1995. Two adjacent N-terminal glutamines of BM-40 (osteonectin, SPARC) act as amine acceptor sites in transglutaminaseC-catalyzed modification.. The Journal of Biological Chemistry 270(40), pp. 23415-23420.
Aeschlimann, D., Kaupp, O. and Paulsson, M. 1995. Transglutaminase-catalyzed matrix cross-linking in differentiating cartilage: identification of osteonectin as a major glutaminyl substrate. Journal of Cell Biology 129(3), pp. 881-892. (10.1083/jcb.129.3.881)
Aeschlimann, D. 1995. Tissue transglutaminase. In: Haeberli, A. ed. Human Protein Data. Weinheim: VCH Verlagsgesellschaft mbH

1994

Aeschlimann, D. and Paulsson, M. 1994. Transglutaminases: protein cross-linking enzymes in tissues and body fluids.. Thrombosis and Haemostasis 71(4), pp. 402-415.

1993

Aeschlimann, D., Wetterwald, A., Fleisch, H. and Paulsson, M. 1993. Expression of tissue transglutaminase in skeletal tissues correlates with events of terminal differentiation of chondrocytes.. The Journal of Cell Biology 120(6), pp. 1461-1470.

1992

Huwyler, J., Aeschlimann, D., Christen, U. and Gut, J. 1992. The kidney as a novel target tissue for protein adduct formation associated with metabolism of halothane and the candidate chlorofluorocarbon replacement 2,2-dichloro-1,1,1-trifluoroethane.. European Journal of Biochemistry / FEBS 207(1), pp. 229-238. (10.1111/j.1432-1033.1992.tb17042.x)
Aeschlimann, D., Paulsson, M. and Mann, K. 1992. Identification of Gln726 in nidogen as the amine acceptor in transglutaminase-catalyzed cross-linking of laminin-nidogen complexes.. Journal of Biological Chemistry 267(16), pp. 11316-11321.
Hedbom, E. et al. 1992. Cartilage matrix proteins. An acidic oligomeric protein (COMP) detected only in cartilage.. Journal of Biological Chemistry 267(9), pp. 6132-6136.

1991

Aeschlimann, D. and Paulsson, M. 1991. Cross-linking of laminin-nidogen complexes by tissue transglutaminase. A novel mechanism for basement membrane stabilization.. Journal of Biological Chemistry 266(23), pp. 15308-15317.

Research Tools

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.

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Influential Research Articles

Original research

Hadjivassiliou, M., Aeschlimann, P., Strigun, A., Sanders, D., Woodroofe, N., and Aeschlimann, D. (2008). Autoantibodies in gluten ataxia recognize a novel neuronal transglutaminase. Ann. Neurol. 64, 332-343. Citations: >100

Szondy, Z., Sarang, Z., Molnar, P., Nemeth, T., Piacentini, M., Mastroberardino, P.G., Falasca, L., Aeschlimann, D., Kovacs, J., Kiss, I., Szegezdi, E., Lakos, G., Rajnavolgyi, E., Birckbichler, P.J., Melino, G.,and Fesus, L. (2003). Transglutaminase 2-/- mice reveal a phagocytosis-associated crosstalk between macrophages and apoptotic cells. Proc. Natl. Acad. Sci. USA 100, 7812-7817. Citations: >160

Grenard, P., Bates, M.K, and Aeschlimann, D. (2001). Evolution of transglutaminase genes: Identification of a gene cluster on human chromosome 15q15. Structure of the genes encoding transglutaminase X and a novel gene family member, transglutaminase Z. J. Biol. Chem. 276, 33066-33078. Citations: >140

Bulpitt, P., and Aeschlimann, D. (1999). New strategy for chemical modification of hyaluronic acid: Preparation of functionalized derivatives and their use in the formation of novel biocompatible hydrogels. J. Biomed. Mater. Res. 47, 152-169. Citations: >290

Gaudry, C.A., Verderio, E., Aeschlimann, D., Cox, A., Smith, C., and Griffin, M. (1999). Cell surface localization of tissue transglutaminase is dependent on a fibronectin binding site in its N-terminal b-sandwich domain. J. Biol. Chem. 274, 30707-30714. Citations: >100

Aeschlimann, D., Kaupp, O., and Paulsson, M. (1995). Transglutaminase-catalyzed matrix cross-linking in differentiating cartilage: Identification of osteonectin as a major glutaminyl substrate. J. Cell Biol.129, 881-892. Citations: >160

Aeschlimann, D., Wetterwald, A., Fleisch, H., and Paulsson, M. (1993). Expression of tissue transglutaminase in skeletal tissues correlates with events of terminal differentiation of chondrocytes. J. Cell Biol. 120, 1461-1470. Citations: >150

Hedbom, E., Antonsson, P., Hjerpe, A., Aeschlimann, D., Paulsson, M., Rosa-Pimentel, E., Sommarin, Y., Wendel, M., Oldberg, Å., and Heinegard, D. (1992). Cartilage matrix proteins: An acidic oligomeric protein (COMP) detected only in cartilage. J. Biol. Chem. 267, 6132-6136. Citations: >330

Aeschlimann, D., and Paulsson, M. (1991). Cross-linking of laminin-nidogen complexes by tissue transglutaminase: A novel mechanism for basement membrane stabilization. J. Biol. Chem. 266, 15308-15317. Citations: >150

Critical Analysis of Research Field

Hadjivassiliou, M, Sanders, D.S., Grünewald, R.A., Woodroofe, N. Boscolo, S., and Aeschlimann, D (2010). Gluten sensitivity: from gut to brain. Lancet Neurol. 9, 318-330. Citations: >120

Aeschlimann, D., and Thomazy, V. (2000). Protein crosslinking in assembly and remodelling of extracellular matrices: The role of transglutaminases. Connect. Tissue Res. 41, 1-27. Citations: >220

Aeschlimann, D., and Paulsson, M. (1994). Transglutaminases: Protein cross-linking enzymes in tissues and body fluids. Thromb. Haemostasis 71, 402-415. Citations: >430

Research Degree Students

PhD Students:

Helen Thomas (2000-04, PhD awarded 2004) 'Characterisation of a novel transglutaminase, TGase 6, and determination of its expression pattern' (prize for best short presentation at 7th International Conference on Transglutaminases and Protein Crosslinking Reactions, Ferrara, Italy, 2002)

Kate Silverthorne (2000-04, PhD awarded 2004) 'Development of 'smart' biomaterials for tissue repair' (prize for best presentation at Smith & Nephew research day, York, 2002)

Sally Rosser Davies (2001-05, PhD awarded 2005) 'Novel transglutaminases: a potential route to healthy skin'

Lorna Fiedler (2003-07, PhD awarded 2007) 'The role of decorin in control of endothelial cell behaviour' (prize for best presentation at the Cardiff Institute for Tissue Engineering and Repair (CITER) meeting 2004; prize for best poster at CITER meeting 2005; prize for short presentation at the British Matrix Biology Society meeting, Manchester, 2005; poster prize at the British Matrix Biology Society meeting, Newcastle, 2006)

Anna Koutoulaki (2004-08, PhD awarded 2008) 'Regulation of interleukin-18 signalling in dendritic cells' (poster prize at Cardiff University postgraduate day 2005; Unilever poster prize at BSODR meeting, Durham, 2007)

Jessica Edwards (2005-08 & 2009-10, PhD awarded 2010) 'Role of transglutaminases in signalling that regulates epithelial responses in wound healing'

Anja Bloom (2008-12, PhD awarded 2012) 'CD59a - a novel role in bone' (prize for presentation at Cardiff University postgraduate day 2011)

Magdalena Adamczyk (2009-13, PhD awarded 2013) 'Biomarkers for arthritis: Regulation of transglutaminase activity by non-conventional export' (2nd prize for poster at BSODR meeting, Bath, 2013; Prize for best presentation 5th UK Purine Club Symposium, Cambridge, 2013; awarded Arthritis Research UK Foundation fellowship, 2014-17)

Lea Bauer (2010-14, PhD awarded 2014) 'Characterisation of G protein-coupled receptor 56-signalling and its potential role in tumour progression'

Andreas Heil (2011-15, PhD awarded 2015) 'Development of a novel 3D human cartilage model system to investigate changes associated with osteoarthritis' (Unilever poster prize at BSODR meeting Bath, 2013; poster prize at Cardiff University postgraduate day 2013)

Ana Mafalda Jegundo dos Reis (2012-16, PhD awarded 2017) 'The role of transglutaminase 6 in gluten-related disorders'

Rhiannon Griffiths (2013-2017, PhD awarded 2017) 'Biomarkers for arthritis: The role of P2X7 receptor in transglutaminase 2 export and activation' (2nd prize for oral presentation at 2nd UK Extracellular Vesicle Forum, Cardiff, 2015; awarded Wellcome Trust ISSF Consolidator Fellowship 2017-18)

Shannon Tuberville (October 2015-) 'Unravelling the mechanism by which mutations in transglutaminase 6 cause ataxia'

Uzma Ghulam (October 2018-) 'Investigating a candidate biomarker of osteoarthritis: Role in pathogenesis and efficacy to diagnose disease.'

Ana Carregosa (October 2018-) 'Validation of a stem cell derived cartilage model for osteoarthritis research and drug screening.'

MSc students:

Dermot Kavanagh (MScD 2005 with distinction) 'An investigation of familial non-syndromic molar oligodontia'

Arash Naseri (MScD 2007 with distinction) 'Towards an understanding of non-syndromic oligodontia'

Nasreen A. Yaqoob (MScD 2010 with distinction) 'Abnormalities in teeth and tooth supporting structures in mice deficient for different matrix proteins'

MSc students (International exchange programs):

Markus Messing (2004-05, Technische Universität Darmstadt, Germany) 'Recombinant production of transglutaminase 6 in E.coli and HEK293 cells'

Carolin Kwas (2014, ERASMUS, Westfälische Wilhelms Universität Münster, Germany) 'Converting targets into diagnostic assays for investigation of osteoarthritis patient samples.'

Antonia Schmidt-Thomee (2018-19, ERASMUS, Universität Leipzig, Germany) 'Characterising mutant proteins causing SCA35.'

Selected Conference Presentations

‘Unconventional protein secretion in innate immunity, a new link between transglutaminase 2 and disease processes.’ Aeschlimann, D. Transglutaminases in Medicine Symposium, Debrecen, Hungary, 2017

‘Transglutaminases: New insights into enzyme regulation and pathophysiology of neurodegenerative disease.’ Aeschlimann, D. Gordon Research Conference on Transglutaminases in Human Disease Processes: Girona, Spain, 2016

'Osteoarthritis biomarker discovery using a 3D human articular cartilage model' Dewitt, S., Heil, A., Waddington R., Archer, C., and Aeschlimann, D. British Society for Oral and Dental Research Meeting, Cardiff, UK, 2015

'Unconventional protein secretion in innate immunity: The role of P2X7R in transglutaminase 2 export and activation' Griffiths, R., Adamczyk, R., Jones, A., and Aeschlimann, D. British Society for Oral and Dental Research Meeting, Cardiff, UK, 2015

'Transglutaminases: Enzyme externalization and extracellular functions' Aeschlimann, D. American Society for Matrix Biology Meeting, Cleveland, OH, USA, 2014

'Signalling regulating active TG2 release from cells' Adamczyk, M., Dewitt, S., Knäuper, V., and Aeschlimann D. Gordon Research Conference on Transglutaminases in Human Disease Processes, Lucca, Italy, 2014

'Mesenchymal TG2 activates epithelial ADAM17: mechanistic link to G-protein coupled receptor signaling' Bauer, L., Edwards, J., Heil, A., Dewitt, S., Biebermann, H., Knäuper, V., and Aeschlimann, D. Gordon Research Conference on Transglutaminases in Human Disease Processes, Lucca, Italy, 2014

'Signalling regulating extracellular transglutaminase levels' Adamczyk, M., Dewitt, S., Knäuper, V., and Aeschlimann D. Annual Meeting of Molecular Biology Society of Japan, Kobe, Japan, 2013

'Neurological dysfunction in patients with newly diagnosed Coeliac disease: A large prospective study' Hadjivassiliou, M., Hoggard, N., Aeschlimann, P., Sanders, D.S., Curry, S., and Aeschlimann, D. International Coeliac Disease Symposium, Chicago, IL, 2013

'A novel 3D in vitro model of human articular cartilage' Heil, A., Blain, E., Waddington, R., Archer, C., and Aeschlimann, D. British Society for Oral and Dental Research Meeting, Bath, UK, 2013

'TGM6 mutations affect protein structure and activity' Adamczyk, M., Heil, A., Weber, J., Hils, M., Beck, K., and Aeschlimann, D. Gordon Research Conference on Transglutaminases in Human Disease Processes, Davidson, NC, USA 2012

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

I am interested in supervising PhD students in the following areas:

Current supervision

Taqwa Abusalem

Research student

Contact Details

AeschlimannDP@cardiff.ac.uk
+44 29225 10651