Dr Verderio Edwards is:
- Module Leader of Cell Signalling and Cancer
- UoA A03 Coordinator (REF 2021)
Research interests include:
The molecular biology of Transglutaminase-2 in physiopathological conditions
Transglutaminase type 2 (TG2) (EC 18.104.22.168) belongs to an emergent class of proteins with distinct molecular activities that function both inside and outside the cell and transit the plasma membrane by unconventional secretion. TG2 has been implicated in the pathogenesis of many apparently unrelated diseases, such as tissue fibrosis, celiac disease, cancers, neurodegenerative disorders, and type II diabetes. Although capable of different biological activities, overall its expression and activation is believed to occur as a response to tissue injury and / or cell stress. Protein cross-linking is the enzymatic reaction for which TG2 is better known, involving an acyl transfer reaction between the gamma carboxamide group of a peptide-bound Gln residue and the epsilon-amino group of a peptide-bound Lys residue or a primary amino group of a polyamine. TG2 causes additional post-translational modifications among which protein deamidation of Gln residues contributes to the development of disorders caused by gluten sensitivity.
The Verderio Edwards' group-interests centre on the function of Transglutaminase-2 (TG2) in adhesion dynamics and the relationship of this with wound healing, tissue fibrosis and cell survival.
Main outcomes and projects:
- Role of TG2 in wound healing and fibrosis. TG2 mediates a novel cell survival pathway independent from the Arg-Gly-Asp (RGD)-main cell adhesion site of fibronectin, and plays a significant role in situations of matrix fragmentation / tissue injury. The cell signalling pathways elicited by TG2-mediated RGD-independent cell adhesion has been dissected and shown to be mediated by extracellular TG2 binding to cell surface receptor Syndecan-4. Work in collaboration with Prof M Griffin (Aston University) (Verderio E et al, 2003. J. Biol. Chem. 278, 42604-42614; Telci D et al. 2008, J. Biol. Chem. 283, 20937-20947) Diagram
- Role of Syndecan-4 in the biological activity of extracellular TG2 in vivo. A joint project with Dr T Johnson, Sheffield University, has identified a cooperative function of TG2 and Syndecan-4 in the development of experimental kidney fibrosis (unilateral ureteric obstruction (UUO) and aristolochic acid nephropathy (AAN)). (Huang L et al 2013, Nephron Extra, 3:12-29; Scarpellini et al. 2014, J Am Soc Nephrol. (Epub ahead of print)
- Characterisation of the heparin binding property of TG2. The affinity binding of TG2 for heparan sulphate (HS) has been demonstrated biochemically by solid binding assays and co-immunoprecipitation, and by double immunofluorescent staining of fixed and stained primary cells. The significance of the syndecan-4/HS - TG2 association in TG2 cell surface trafficking/localisation has been investigated in primary cell models (Scarpellini A et al 2009. J. Biol. Chem. 284: 18411-18423, Lortat-Jacob H & Burhan I et al 2012. J. Biol. Chem. 287:18005-18017) Diagram
- A differential proteomic approach to identify disease gene-associated proteins in kidney membranes. Discovery of TG2- associated proteins in normal and diseased kidney cell membranes has set the basis for mapping the TG2 interactome in renal pathophysiological conditions. The project is being carried out in collaboration with the proteomics group at Nottingham Trent University (Dr David Boocock- John van Geest Cancer Research Centre), jointly with Dr T Johnson, Sheffield University, with support from Kidney Research UK.
The team have extensively collaborated with CNRS- Grenoble Institut de Biologie Structurale, Grenoble (Prof H. Lortat-Jacob) for surface plasmon resonance studies and the Department of Biological Sciences of University of Bologna (Prof D. Serafini-Fracassini and Prof S. Del Duca), for work with pollen transglutaminase.
Current Reserch Associates
- Elisa Tonoli
- Adeola Atobatele (Grace)
Research Fellows (Present and past):
- Dr Alessandra Scarpellini (now Manager at Essen BioScience-Sartorious)
- Dr Nina Schroder (now at Sygnature Discovery)
Current PhD Students :
- Adeola Atobatele (Grace)
- Elisa Tonoli
- Maria Pia Savoca
Previous PhD Students:
- Shakthi Dookie
- Alessandra Scarpellini
- Izhar Burhan
- Giulia Furini
Opportunities to carry out postgraduate research towards an MPhil / PhD exist in all the areas identified above and further information may be obtained from the https://www.ntu.ac.uk/research/research-degrees-at-ntu.
Sponsors and collaborators
Research funding includes:
- VU Medical School Amsterdam (2019) €10,000
- UCB Pharmaceuticals (2017-2018) £105, 740
- Kidney Research UK (2013-2016), £66,440 -Transglutaminase-2 (TG2) interactome in experimental kidney fibrosis: accelerated identification of TG2 therapeutic targets.
- Wellcome Trust (2009 to 2013), £322,000 ( £146,994 to NTU) - Does Syndecan-4 play a crucial role in the development of kidney scarring by acting as a novel cell surface co receptor for Transglutaminase-2, E Verderio (joint PI) and T Johnson,
- iNET East Midlands (2009 to 2010), £24,634 -Tissue transglutaminase (TG2) - a candidate susceptibility gene for Type 2 Diabetes, E Verderio (PI), D Hughes and S Chan,
- British Council-CRUI (2006 to 2007), £12,000 - Influence of climatic changing factors on the allergenicity of pollen and allergic respiratory diseases: the involvement of pollen transglutaminase
- EPSRC (2003 to 2006), £160,000 - The use of tissue transglutaminase as a novel biocatalyst in the modification of collagen for development of new biomaterial, E Verderio (Co-I) and M Griffin (PI).
Proteomic Profiling Reveals the Transglutaminase-2 Externalization Pathway in Kidneys after Unilateral Ureteric Obstruction. Furini, G., Schroeder, N., Huang, L., Boocock, D., Scarpellini, A., Coveney, C., Tonoli, E., Ramaswamy, R., Ball, G., Verderio, C., Johnson, T.S., Verderio, E.A.M. Journal of the American Society of Nephrology. 2018, 29:880-905.
Interplay between transglutaminases and heparan sulphate in progressive renal scarring. Burhan, I., Furini, G., Lortat-Jacob, H., Atobatele, A.G., Scarpellini, A., Schroeder, N., Atkinson, J., Maamra, M., Nutter, F.H., Watson, P., Vinciguerra, M., Johnson, T.S, Verderio, E. Scientific Reports. 2016, 6:31343.
Syndecan-4 knockout leads to reduced extracellular transglutaminase-2 and protects against tubulointerstitial fibrosis. Scarpellini A, Huang L, Burhan I, Schroeder N, Funck M, Johnson TS, Verderio EA. Journal of the American Society of Nephrology. 2014, 25:1013-27.
Transglutaminase-2 interaction with heparin: identification of a heparin binding site that regulates cell adhesion to fibronectin-transglutaminase-2 matrix. Lortat-Jacob H, Burhan I, Scarpellini A, Thomas A, Imberty A, Vivès RR, Johnson T, Gutierrez A, Verderio E, Journal of Biological Chemistry, 2012, 287:18005-18017
A crucial sequence for transglutaminase type 2 extracellular trafficking in renal tubular epithelial cells lies in its N-terminal -sandwich domain. Chou CY, Streets AJ, Watson PF, Huang L, Verderio E, Johnson TS, Journal of Biological Chemistry, 2011, 286:27825-27835
Simulated environmental criticalities affect transglutaminase of Malus and Corylus pollens having different allergenic potential. Iorio RA, Di Sandro A, Paris R, Pagliarani G, Tartarini S, Ricci G, Serafini-Fracassini D, Verderio E, Del Duca S, Amino Acids, 2011, 42:1007
An extracellular transglutaminase is required in apple pollen tube growth. Di Sandro A, Del Duca, S, Verderio E, Hargreaves A, Bonner P, Griffin M, Iorio R, Scarpellini A, Serafini-Fracassini D, Biochemical Journal, 2010, 429: 261-271
Heparan sulphate proteoglycans are receptors for the cell-surface trafficking and biological activity of transglutaminase-2. Scarpellini A, Germack R, Lortat-Jacob H, Muramatsu T, Billett E, Johnson T, Verderio E, Journal of Biological Chemistry, 2009, 284:18411-1842
Fibronectin-tissue transglutaminase matrix rescues RGD-impaired cell adhesion through syndecan-4 and beta(1) integrin co-signaling. Telci D, Wang Z, Li X, Verderio EA, Humphries MJ, Baccarini M, Basaga H, Griffin M, Journal of Biological Chemistry, 2008, 283:20937-41See all of Elisabetta Verderio Edwards's publications...
- Chronic kidney disease
- Wound healing
- Transglutaminase type 2 (TG2)