Dr Russell Collighan

Member of research strand 'Development of novel drugs, formulations and tissues to support healthy ageing' - Aston Research Centre for Healthy Ageing

Career history 2009-date

Current Research Interests

Our research is focussed on a group of enzymes called transglutaminases. Transglutaminases are found in many different organisms including microbes, plants and mammals. These enzymes are responsible for a variety of post-translational modifications of proteins, in particular cross-linking of proteins into large molecular weight polymers that are more resistant to degradation. This process is important for the stability of skin, hair, blood clots and the extracellular matrix surrounding cells. Of particular interest is the tissue transglutaminase (TG2), which is important in inflammation, matrix deposition, cell adhesion and cell migration. Consequently, these functions have relevance to a broad range of physiological and pathological processes such as wound healing, tissue fibrosis and scarring, tumour progression, cystic fibrosis, and neurodegeneration.

We have an established programme of research into the molecular mechanisms by which TG2 exerts its physiological and pathological effects. To do this, we use a variety of cell systems which can be engineered to express different site-directed mutant TG2 enzymes that we have produced. We are also developing a range of targeted irreversible inhibitors of TG2 as potential novel therapeutic agents for TG2-associated pathologies. We are also interested in exploiting the matrix cross-linking properties of transglutaminases for the development of stable, biocompatible biomaterials that can be tailored for a variety of biological and physical environments, for example soft tissue or bone repair.

Recent Publications

• Rauhavirta, T., Qiao, S-W., Jiang, Z., Myrsky, E., Loponen, J., Korponay-Szabó, I.R., Salovaara, H., Garcia-Horsman, J.A., Venäläinen, J., Männistö, P.T., Collighan, R., Mongeot, A., Griffin, M., Mäki, M., Kaukinen, K. & Lindfors, K. (2010). Epithelial transport and deamidation of gliadin peptides – a role for coeliac disease patient IgA. Clinical & Experimental Immunology (in press)

• Kotsakis, P., Wang, Z., Collighan, R. & Griffin, M. (2010). The role of tissue transglutaminase (TG2) in regulating the tumour progression of the mouse colon carcinoma CT26. Amino Acids (in press)

• Bergamini, C.M., Collighan, R.J. & Griffin, M. (2010). Structure and Regulation of Type 2 Transglutaminase in Relation to its Physiological Functions and Pathological Roles. Advances in Enzymology: and Related Areas in Molecular Biology Volume 78 (in press)

• Wang, Z., Collighan, R.J., Gross, S.R., Danen, E.H.J., Orend, G.,Telci, D. & Griffin, M. (2010). RGD-independent cell adhesion via a tissue transglutaminase-fibronectin matrix promotes fibronectin fibril deposition and requires syndecan-4/2 and α5β1 integrin co-signalling. Journal of Biological Chemistry (in press)

• Daneshpour, N., Collighan, R., Griffin, M., Perrie, Y.P. (2010). Targeted delivery of a novel group of site directed transglutaminase inhibitors to the liver using liposomes: a new approach for the potential treatment of liver fibrosis. Journal of Drug Targeting (in press)

• Bergamini, C.M., Dondi, A., Lanzara, V., Squerzanti, M., Cervellati, C., Montin, K., Mischiati , C., Tasco, G., Collighan, R., Griffin, M. & Casadio, R. (2010). Thermodynamics of binding of regulatory ligands to tissue transglutaminase. Amino Acids 39 (1): 297-304

• Chau, D.Y.S., Tint, N.L., Collighan, R.J., Griffin, M., Dua, H.S., Shakesheff, K.M. & Rose, F.R.A.J. (2010). The Visualisation of Vitreous Using Surface Modified Poly(DL-lactic-co-glycolic acid) Microparticles. British Journal of Ophthalmology 94: 648-653

• Caja, S., Myrsky, E., Korponay-Szabo, I.R., Nadalutti, C., Sulic, A-M., Lavric, M., Sblattero, D., Marzari, R., Collighan, R., Mongeot, A., Griffin, M., Mäki, M., Kaukinen, K. & Lindfors, K. (2010). Inhibition of transglutaminase 2 enzymatic activity ameliorates the anti-angiogenic effects of coeliac disease autoantibodies. Scandinavian Journal of Gastroenterology 45 (4): 421-427.

• Telci, D., Collighan, R.J., Basaga, H. & Griffin, M. (2009). Increased TG2 expression can result in induction of TGFβ1 causing increased synthesis and deposition of matrix proteins which can be regulated by nitric oxide. Journal of Biological Chemistry 284 (43): 29547-29558

• Myrsky, E., Caja, S., Simon-Vecsei, Z., Korponay-Szabo, I.R., Nadalutti, C., Collighan, R., Mongeot, A., Griffin, M., Mäki, M., Kaukinen, K. & Lindfors, K. (2009). Celiac disease IgA modulates vascular permeability in vitro through the activity of transglutaminase 2 and RhoA. Cellular and Molecular Life Sciences 66 (20): 3375-3385.

• Damodaran, G, Collighan, R, Griffin, M, Navsaria, H & Pandit, A. (2009) Tailored laminin-332 alpha3 sequence is tethered through an enzymatic linker to a collagen scaffold to promote cellular adhesion. Acta Biomaterialia 5 (7): 2441-2450

• Collighan, R. & Griffin, M. (2009). Transglutaminase 2 cross-linking of matrix proteins – biological significance and medical applications. Amino Acids 36 (4): 659-670.

• Garcia, Y., Hemantkumar, N., Collighan, R., Griffin, M. & Pandit, A. (2009). In-vitro Characterization of a Collagen Scaffold Enzymatically Crosslinked with a Tailored Elastin-Like Polymer. Tissue Engineering 15 (4): 887-899

• Damodaran, G., Collighan, R., Griffin, M. & Pandit, A. (2009). Tethering a laminin peptide to a crosslinked collagen scaffold for biofunctionality. Journal of Biomedical Materials Research Part A 89 (4):1001-1010.

• Griffin, M., Mongeot, A., Collighan, R., Saint, R.E., Jones. R.A., Coutts, I.G.C. & Rathbone, D.L. (2008). Synthesis of Potent Water-soluble Tissue Transglutaminase Inhibitors. Bioorganic & Medicinal Chemistry Letters 18 (20):5559-5562

• Garcia, Y., Wilkins, B., Collighan, R.J., Griffin, M. & Pandit, A. (2008). Towards development of a dermal rudiment for enhanced wound healing response. Biomaterials 29 (7):857-868.

• Damodaran, G., Collighan, R., Griffin, M. & Pandit, A. (2007). Tethering of designer peptide sequence on a cross-linked collagen scaffold. Tissue Engineering. 13 (7): 1761-1761.

• Chau, D.Y.S., Collighan, R.J. & Griffin, M. (2007). Collagen: Structure and Modification for Biomedical Applications. In “Trends in Biomaterials Research”. Ed. Patrick J. Pannone (Nova Publishers).

• Garcia, Y., Collighan, R., Griffin, M. & Pandit, A.S. (2007). Assessment of Cell Viability in a Three-Dimensional Enzymatically Cross-linked Collagen Scaffold. Journal of Materials Science: Materials in Medicine 18 (10): 1991-2001.

• O’Halloran, D., Collighan, R.J., Griffin, M. & Pandit, A.S. (2006). Characterisation of a microbial transglutaminase cross-linked type II collagen scaffold. Tissue Engineering 12 (6):1467-1474

• O’Halloran, D., White, M., Collighan, R.J., Griffin, M. & Pandit, A.S. (2005). Scaffold characterisation for nucleus pulposus regeneration. European Cells and Materials 10 (Suppl. 3):9.

• Chau, D.Y.S., Collighan, R.J., Verderio-Edwards, E., Addy, V.L. & Griffin, M. (2005). The Cellular response to transglutaminase-cross-linked collagen. Biomaterials 26 (33): 6518-6529.

• Broderick, E.P., O’Halloran, D.M., Rotchev, Y., Collighan, R.J., Griffin, M. & Pandit, A. (2005). Enzymatic stabilization of gelatin-based scaffolds. Journal of Biomedical Materials Research Part B: Applied Biomaterials 72B (1): 37-42.

• O'Halloran, D., Garcia, Y., Broderick, E., Rotchev, Y., Griffin, M., Collighan, R. & Pandit, A. (2004). Novel Method for Stabilising Gelatin Based Scaffolds. Proceedings of the 10th Annual Conference of the Section of Bioengineering, Royal Academy of Medicine in Ireland (D.P. FitzPatrick, B.A.O. McCormack, T.M. McGloughlin, Editors).

• Skill, N.J., Johnson, T.S., Coutts, I., Saint, R., Fisher, M., Huang, L., El Nahas, A.M., Collighan R.J. & Griffin, M. (2004). Inhibition of transglutaminase (Tg) activity reduces extracellular matrix (ECM) accumulation induced by high glucose levels in proximal tubular epithelial cells. Journal of Biological Chemistry 279 (46): 47754-47762.

• Collighan, R., Clara, S., Li, X., Parry, J. & Griffin, M. (2004). Transglutaminases as tanning agents for the leather industry. Journal of the American Leather Chemists Association 99 (7): 289-298.

• Senior, K., Griffin, M. & Collighan, R. (2003). Novel approach to improving enzyme penetration.  BLC Journal Volume 46 November.

• Collighan, R. & Griffin, M. (2003). Transglutaminases in the Leather industry. BLC Journal Volume 46 January.

• Collighan, R., Cortez, J. & Griffin, M. (2002). The Biotechnological Application of Transglutaminases. Minerva Biotechnologica 14 (2): 143-148.

• Balklava, Z., Verderio, E., Collighan, R., Gross, S., Adams, J. & Griffin, M. (2002). Analysis of Tissue Transglutaminase Function in the Migration of Swiss 3T3 Fibroblasts. The Active-state Conformation of the Enzyme does not Affect Cell Motility but is Important for its Secretion. The Journal of Biological Chemistry 277 (19):16567-16575.

• Jones, R. C. F., Collighan, R. J., Crane, J., Hodges, N. J., Ling, M. S. & Stroud, J. (2002). New 6-Ethoxyquinolines as Simple Optoquine Analogues. Synthetic Communications 32 (20): 3185-3191.

• Collighan, R. J. & Woodward, M. J. (2001). The SEF14 fimbrial antigen of Salmonella enterica serovar Enteritidis is encoded within a pathogenicity islet. Veterinary Microbiology 80 (3):235-245.

• Collighan, R. J., Walker, S. L. & Woodward, M.J. (2000). Sequence analysis and distribution in Salmonella enterica serovars of IS3-like elements. International Journal of Medical Microbiology 290 (7), 619-626.

• Collighan, R. J., Naylor, R. D., Martin, P. K., Cooley, B. A., Buller, N. & Woodward, M. J. (2000). A spirochete isolated from a case of severe virulent ovine foot disease is closely related to a Treponeme isolated from human periodontitis and bovine digital dermatitis. Veterinary Microbiology 74, 249-257.

• La Ragione, R. M., Collighan, R. J. & Woodward, M. J. (1999). Non-curliation of Escherichia coli O78 : K80 isolates associated with IS1 insertion in csgB and reduced persistence in poultry infection. Fems Microbiology Letters 175, 247-253.

• Collighan, R. J., Bennett, A. J. & Coleman, G. (1998). Cloning, mapping and identification of the Aeromonas salmonicida fstA, fepA and irpA genes, encoding the 86, 82 and 74 kDa iron-regulated outer membrane proteins, respectively. Fish Pathology 33, 239-246.

• Allen-Vercoe, E., Collighan, R. & Woodward, M. J. (1998). The variant rpoS allele of S. enteritidis strain 27655R does not affect virulence in a chick model nor constitutive curliation but does generate a cold-sensitive phenotype. Fems Microbiology Letters 167, 245-253.

• Collighan, R. J. & Woodward, M. J. (1997). Sequence analysis and distribution of an IS3-like insertion element isolated from Salmonella enteritidis. Fems Microbiology Letters 154, 207-213.

• Collighan, R. J. & Woodward, M. J. (1997). Spirochaetes and other bacterial species associated with bovine digital dermatitis. Fems Microbiology Letters 156, 37-41

• Coleman, G., Collighan, R. J. & Dodsworth, S. J. (1995). Glycogen, the Preferred Energy-Source For Extracellular Protein-Formation and Growth of Aeromonas salmonicida. Journal of Fish Diseases 18(3), 221-228.

Conference Proceedings

• Daneshpour, N., Collighan, R., Perrie, Y., Mongeot, A., Griffin, M. (2009). A new approach to the treatment of liver cirrhosis: transglutaminase inhibitors and potential delivery systems. Journal of Pharmacy and Pharmacology 61: A19.

• Garcia, Y., Naik, H., Collighan, R., Griffin, M., Rodriguez-Cabello, J.C., Pandit, A. (2009). Preferential cellular behaviour is seen with a collagen-elastin-like polypeptide scaffold. Tissue Engineering Part A 14(5):769

• Daneshpour, N., Collighan, R., Perrie, Y., Telci, D., Mongeot, A., Rathbone, D., Griffin, M. (2008). Investigation of fluorescent derivatives as potential probes for novel transglutaminase inhibitors. Journal of Pharmacy and Pharmacology 60:A56-A57

• Chau, D.Y.S., Tint, N.L., Joy, S., Collighan R.J., Griffin, M., Rose, F.R.A.J., Dua, H.S. & Shakesheff, K.M. The Development of Bioadhesive Microparticles for Clinical and Regenerative Medical Applications. TERMIS North America 2008 Annual Conference & Exposition.San Diego, US, December 7 - 10, 2008

• Tint, N.L., Chau, D.Y.S., Collighan, R., Griffin, M., Shakesheff, K.M., Dua, H.S. & Rose, F.R.A.J. Surface Modified Microparticles For Visualisation of Vitreous. European Association for Vision and Eye Research (EVER) 2008 congress, October 1-4 2008, Portoroz, Slovenia

• Daneshpour, N., Collighan, R., Perrie, Y., Mongeot, A., Rathbone, D., Lambert, P. & Griffin, M. Synthesis of a novel fluorescent transglutaminase inhibitor for controlled release from catheters and other implant devices. 35^th Controlled Release Society Annual Meeting and Exposition, New York, 12-16 July 2008.

• Telci, D., Collighan, R. Basaga, H. & Griffin, M. Nitric oxide is an important regulator of TG2 activity in the extracellular environment by mediating its dual role as matrix crosslinker and cell surface adhesion protein. XXIst Federation of European Connective Tissue Societies (FECTS) Meeting, Marseille, 9-13 July 2008.

• Chau, D., Collighan, R., Fortunati, D., Garcia, Y., Pandit, A. & Griffin, M. Enzymatically cross-linked collagen as a tissue scaffold. XXIst Federation of European Connective Tissue Societies (FECTS) Meeting, Marseille, 9-13 July 2008.

• Mongeot, A., Rathbone, D., Collighan, R. & Griffin, M. Novel compounds for reducing matrix accumulation and fibrosis by the inhibition of tissue transglutaminase (TG2). XXIst Federation of European Connective Tissue Societies (FECTS) Meeting, Marseille, 9-13 July 2008.

• Garcia, Y., Naik, H., Collighan, R., Griffin, M., Rodriguez Cabello, J.C. & Pandit, A. In-vitro Characterization of an Enzymatically Cross-linked Collagen-Elastin Like Polymer Scaffold. 8th World Biomaterials Congress, Amsterdam, The Netherlands, May 28 -  June 1, 2008.

• Garcia, Y., Collighan, R., Griffin, M. & Pandit, A. Stimulation of Angiogenesis in an Enzymatically Cross-linked Collagen Scaffold. TERMIS EU Meeting, London, Sept. 4-7, 2007.

• Telci, D., Collighan, R., Li, X., Basaga, H. & Griffin, M. Nitric Oxide may be an Important Regulator of TG2 Activity and Function in the Extracellular Environment. 9th International Conference on Protein Crosslinking and Transglutaminases (PCL9), Marrakech, Morocco, Sept. 1-5, 2007.

• Garcia, Y., Collighan, R., Griffin, M. & Pandit, A. Stimulation of Angiogensis in a Transglutaminase Cross-linked Collagen Scaffold Used in Dermal Repair. 9th International Conference on Protein Crosslinking and Transglutaminases (PCL9), Marrakech, Morocco, Sept. 1-5, 2007.

• Mongeot, A., Coutts, I., Saint, R., Rathbone, D., Collighan, R. & Griffin, M. Development of Enzyme-Specific Transglutaminase Inhibitors. 9th International Conference on Protein Crosslinking and Transglutaminases (PCL9), Marrakech, Morocco, Sept. 1-5, 2007.

• Garcia, Y. Damodaran, G., Collighan, R., Griffin, M. & Pandit, A. Structural and Physicochemical Characterisation of an Enzymatically Cross-linked Collagen Scaffold. Society for Biomaterials 2006 Annual Meeting and Exposition, Pittsburgh, Pennsylvania, USA, April 26-29, 2006.

• Damodaran, G., Collighan, R., Griffin, M. & Pandit, A. A Collagen scaffold with motif of laminin 5 a 3 chain. Bioengineering In Ireland Conference, Galway, January 27-28, 2006.

• Halloran, D., Collighan, R., Griffin, M. & Pandit, A. Development Of A Collagen Type II Scaffold For Intervertebral Disc Repair. 8^th Annual Meeting of Tissue Engineering Society International. Shanghai, China, 22-25^th October, 2005.

• Parsons, R., Collighan, R., Griffin, M. & Szakacs, G. Biochemical analyses of transglutaminase from Streptomyces. Biocatalysis: Enzymes, Mechanisms and Bioprocesses - a Biochemical Society Focused Meeting in association with Pro-Bio Faraday Annual Conference, 21-22^nd November, 2005.

• Chau, D., Collighan, R., Ye, L., Prince, M., Verderio, E., Addy, V., Ma, X. & Griffin, M. The use of transglutaminase as a biocatalyst in the modification of collagen for the development of biomaterials. 8th International Conference on Protein Crosslinking and Transglutaminases (PCL8), Sept. 1-4, 2005.

• Parsons, R., Collighan, R., Griffin, M. & Szakacs, G. Biochemical analyses of transglutaminase from strains of Streptomyces. 8th International Conference on Protein Crosslinking and Transglutaminases (PCL8), Sept. 1-4, 2005.

• Halloran, D., Collighan, R., Griffin, M. & Pandit, A. Development Of A Collagen Type II Scaffold For Intervertebral Disc Repair. 8th International Conference on Protein Crosslinking and Transglutaminases (PCL8), Sept. 1-4, 2005.

• O’Halloran, D., White, M., Collighan, R.J., Griffin, M. & Pandit, A.S. Scaffold characterisation for nucleus pulposus regeneration. ECM VI/SRNI: Spinal Motion Segment: From Basic Science to Clinical Application, July 4-7, 2005.

• Garcia, Y., Collighan, R., Griffin, M. & Pandit, A. Cell Viability in an Enzymatically Stabilised Collagen Scaffold. Society for Biomaterials 30^th Annual Meeting and Exposition. New applications and Technologies, April 27-30, 2005.

• Halloran, D., Collighan, R., Griffin, M. & Pandit, A. Development Of A Collagen Type II Scaffold For Intervertebral Disc Repair. Society for Biomaterials 30^th Annual Meeting and Exposition. New applications and Technologies, April 27-30, 2005.

• Halloran, D., Garcia, Y., Broderick, E., Rotchev, Y., Griffin, M., Collighan, R. & Pandit, A. Novel method for stabilising gelatin based scaffolds. Bioengineering In Ireland Conference, January 30-31, 2004.

• Collighan, R. and Griffin, M. Leather Protein Modification by Transglutaminase.  Pro-Bio Faraday Partnership Annual Conference: “Biocatalysis for Manufacture:  Current Practice and Future Opinions”.  Heriot-Watt University, 5-6 November 2003.

• Parsons, R. L., Collighan, R. J. & Griffin, M. Isolation, Characterisation and Application of Novel Microbial Protein Cross-Linking Enzymes. Pro-Bio Faraday Partnership Annual Conference: “Biocatalysis for Manufacture:  Current Practice and Future Opinions”.  Heriot-Watt University, 5-6 November 2003.

• Collighan, R. J. & Woodward, M. J. The SEF14 fimbrial operon of Salmonella enteritidis lies in a pathogenicity island which includes virulence plasmid encoded gene homologues. Society for General Microbiology 142 Ordinary SGM meeting. JAN 5-7, 1999.

• Collighan, R. J., Bennett, A.J. & Coleman, G. Cloning, mapping and identification of the Aeromonas salmonicida fstA, fepA and irpA genes, encoding the 86, 82 and 74 kDa iron-regulated outer membrane proteins, respectively. 4th International Symposium of the Japanese-Society-of-Fish-Pathology. OCT 03-06, 1997.

• Collighan, R. J. & Coleman, G. Molecular Biological Studies on the Iron Transport Systems of Aeromonas salmonicida. Seventh International Conference of the European Association of Fish Pathologists: "Diseases of Fish and Shellfish". SEPT 10-15, 1995.

• Dodsworth, S. J., Collighan, R.J. & Coleman, G. The ability of maltose inducible porin, LamB, antibody to agglutinate Aermonas salmonicida following growth in different carbon sources. Sixth International Conference of the European Association of Fish Pathologists: "Diseases of Fish and Shellfish". SEPT 5-10, 1993.

Patents

• Addy, V., Griffin, M., Collighan, R. & Clara, S. (2005). Enzymatic Treatment of Hides and Leather. WO2005007897

• Griffin, M., Collighan, R., Chau, D. & Verderio-Edwards, E. (2006). Medical Implant Materials. WO2006027622

•  Lambert, P.A., Griffin. M., Collighan, R. & Rathbone D.L. (2007). Medical devices and coatings therefor. WO2007010201