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John Crean

Associate Professor

School Of Biomolecular & Biomed Science
Conway Institute
Belfield
Dublin 4

Tel: +353 1 7166747
Email: john.crean@ucd.ie

Biography

John is a UCD graduate (Biochemistry, B.Sc.). After completing his Masters in Clinical Biochemistry in Boston University and UCD, John joined the PhD programme at the University of Bristol under the direction of Professor Vic Duance in the Muscle and Collagen Research Centre. There began his love/hate relationship with matrix biology and fibrotic disease. Graduating in 1998, he joined the Matrix Group at R+D Systems in Oxford. He returned to academia in 2000, firstly at the University of Liverpool, and latterly in UCD under the guidance of Hugh Brady and Catherine Godson in the Mater Misericordiae Hospital. In 2002 he was awarded a HRB Career Development Fellowship and relocated to the laboratory of Finian Martin in the Biotechnology Centre in Belfield. In 2005, John joined the staff of Pharmacology, where he remains to this day. John is one of Principal Investigators in the SFI-funded Diabetes Research Centre, his group working mainly on aspects of cell-matrix interactions and matricellular signaling. His contributions to this field have included several important papers identifying receptors and downstream effector molecules belong to the CCN family. Their most recent studies have characterised interplay between receptor activated networks that regulate cell fate and differentiation in nephropathy, identifying an autocrine regulatory loop in TGFbeta signaling that plays a critical role in the regulation of fibrotic responses.

Research Links:  SBBS Research  |  Mechanisms of Disease Research in SBBS 

Professional

Honours and Awards

Year: 1996.
Title: Sofamor-Danek Award for Basic Science
Year: 1997.
Title: Young Scientist of the Year

Associations

Association: International CCN Society, Function/Role: Member
Association: American Association for the Academy of Sciences, Function/Role: Member
Association: American Society for Experimental Biology, Function/Role: Member
       

Committees

Committee : UCD Human Research Ethics
Committee : UCD Conway Institute Imaging Steering Committee
Committee : Bachelor of Health and Life Sciences Programme Board
Committee : School of Biomolecular and Biomedical Sciences Teaching and Learning Committee

Employment

Employer: U.C.D.
Position: Honorary Lecturer Medicine & Career track Investigator, Conway Institue
Employer: U.C.D.
Position: Lecturer, HRB Career Development Fellow, Dept Medicine & Therapeutics
Employer: Mater Hospital, Dublin
Position: Postdoctoral Fellow Dept. Medicine & Therapeutics
Employer: University of Liverpool
Position: Postdoctoral Fellow Dept Veterinary Pathology
Employer: R+D Systems Europe Ltd
Position: Postdoctoral Research Scientist
Employer: Uni. Bristol
Position: Research Assistant, Muscle & Collagen Research Grp
Employer: Boston University
Position: Research Associate Section of Gastroenterology
Employer: St.Vincents University Hospital
Position: Lecturer (School of Nursing) Education & Research Cnt

Education

Year 1993 Institution: University College Dublin
Qualification: MSc Subject:
Year 1998 Institution: University of Bristol
Qualification: PhD Subject:
Year 1990 Institution: University College Dublin
Qualification: BSc Subject:
 

Consultancy

Client: European Medicines Agency

Outreach Activities

SBBS representative Access Science 2008-09
   

Publications

 

Book Chapters

Crean, JK., Brady, HR and Rabb, H.; (2004) 'Cell-cell and cell matrix interactions' In: Barry Brenner (eds). The Kidney. Philadelphia: Saunders, Elsevier. , pp.199-229 [Details]
 

Peer Reviewed Journals

Beaton H, Andrews D;Parsons M;Murphy M;Gaffney A;Kavanagh D;McKay GJ;Maxwell AP;Taylor CT;Cummins EP;Godson C;Higgins DF;Murphy P;Crean J (2016) 'Wnt6 regulates epithelial cell differentiation and is dysregulated in renal fibrosis'. American journal of physiology. Renal physiology, . [DOI] [Details]
Oliviero, G; Brien, GL; Watson, A; Streube, G; Jerman, E; Andrews, D; Doyle, B; Munawar, N; Wynne, K; Crean, J; Bracken, AP; Cagney, G. (2016) 'Dynamic protein interactions of the Polycomb Repressive Complex 2 during differentiation of pluripotent cells'. Molecular and Cellular Proteomics, . [DOI] [Details]
De Chiara L, Crean J (2016) 'Emerging Transcriptional Mechanisms in the Regulation of Epithelial to Mesenchymal Transition and Cellular Plasticity in the Kidney'. Journal of clinical medicine, 5 (1). [DOI] [Details]
McKay, GJ; Kavanagh, D;, Crean, JK; Maxwell AP (2015) 'Bioinformatic Evaluation of Transcriptional Regulation of WNT Pathway Genes with reference to Diabetic Nephropathy'. Journal of Diabetes Research, . [DOI] [Details]
Dodd TK, Crean J, de Chiara L, Higgins DF, Belton O. (2015) 'The role of miR302 and Let7 in macrophage polarisation'. Journal of the American Society of Nephrology : JASN, 26 ((NA)):695A. [Details]
Beaton H, Gaffney A, Godson C, Higgins DF, Crean J. (2014) 'Wnt6 regulates epithelial cell fate specification during kidney development and in adult renal cells'. Journal of the American Society of Nephrology : JASN, 25 ((NA)):169A. [Details]
Faherty, N., O'Donovan, H., Kavanagh, D., madden, S., McKay, GJ, Maxwell, AP., Martin, F., Godson, C and Crean, J. (2013) 'TGFβ and CCN2/CTGF mediate actin related gene 3 expression by differential E2F1/CREB activation'. BMC Genomics, . [Details]
Hookham MB, O'Donovan HC, Church RH, Mercier-Zuber A, Luzi L, Curran SP, Carew RM, Droguett A, Mezzano S, Schubert M, White MF, Crean JK, Brazil DP (2013) 'Insulin receptor substrate-2 is expressed in kidney epithelium and up-regulated in diabetic nephropathy'. FEBS Journal, . [DOI] [Details]
David H Kavanagh, David A Savage, Christopher C Patterson, Amy Jayne McKnight John Crean, Alexander P Maxwell, Gareth J McKay. (2013) 'Haplotype association analysis of genes within the WNT signalling pathways indiabetic nephropathy BMC Nephrology 2013, 14:126'. JOURNAL OF NEPHROLOGY, . [Details]
O'Donovan, HC,Hickey, F,Brazil, DP,Kavanagh, DH,Oliver, N,Martin, F,Godson, C,Crean, J (2012) 'Connective tissue growth factor antagonizes transforming growth factor-beta 1/Smad signalling in renal mesangial cells'. Biochemical Journal, 441 :499-510. [DOI] [Details]
Kavanagh D, Gaffney A, Murphy M, Faherty N, Andrews D, Higgins DF, McKay G, Maxwell P, Godson C and Crean J. (2012) 'Wnt6 is increased in diabetic nephropathy and modulates de novo tubulogenesis and opposes TGF-beta mediated epithelial cell differentiation in vitro'. Journal of the American Society of Nephrology : JASN, 23 ((NA)):146A. [Details]
O'Donovan HC, Hickey F, Brazil DP, Kavanagh DH, Oliver N, Martin F, Godson C, Crean J (2012) 'Connective tissue growth factor antagonizes transforming growth factor-β1/Smad signalling in renal mesangial cells'. Biochem J, 441 :499-510. [Details]
Faherty N, Curran SP, O'Donovan H, Martin F, Godson C, Brazil DP, and Crean J (2012) 'CCN2/CTGF increases expression of miR-302 microRNAs, which target the TGFβ type II receptor with implications for nephropathic cell phenotypes'. Journal of Cell Science, . [Details]
Rooney, B,O'Donovan, H,Gaffney, A,Browne, M,Faherty, N,Curran, SP,Sadlier, D,Godson, C,Brazil, DP,Crean, J; (2011) 'CTGF/CCN2 activates canonical Wnt signalling in mesangial cells through LRP6: Implications for the pathogenesis of diabetic nephropathy'. FEBS Letters, 585 :531-538. [DOI] [Details]
Smith, J. Meehan, M., Crean J. and McCann A; (2011) 'Alpha T-catenin (CTNNA3); A gene in the hand is worth two in the nest'. Cellular and Molecular Life Sciences, 68 (15):2493-2498. [Details]
Kavanagh DH, Savage DA, Patterson CC, McKnight AJ, Crean JK ; (2011) 'Association Analysis of Canonical Wnt Signalling Genes in Diabetic Nephropathy'. PLoS ONE, 6 (8). [Details]
Browne, JG., Ho, SL., Kadare, SJ., Kane, R., Oliver, N., Clark, AF., O'Brien, CJ., Crean, JK. ; (2010) 'The Effect Of CTGF On Trabecular Meshwork Cells And The Implications For Pseudoexfoliative Syndrome'. IOVS, . [Details]
Brennan EP, Ehrich M, Brazil DP, Crean JK, Murphy M, Sadlier DM, Martin F, Godson C, van den Boom D, Maxwell AP, Savage DA.; (2010) 'DNA methylation profiling in cell models of diabetic nephropathy'. Epigenetics : official journal of the DNA Methylation Society, 16 (5). [Details]
Nyhan KC, Faherty N, Murray G, Cooey LB, Godson C, Crean JK, Brazil DP.; (2010) 'Jagged/Notch signalling is required for a subset of TGFBeta1 responses in human kidney epithelial cells'. Biochima Et Biophysica Acta - Molecular Cell Research, 1803 :1386-1395. [Details]
Rooney B, O'Donovan, H., Browne, M., Gaffney, A., Curran, SP., Brazil, DP. Godson, C., Sadlier, D and Crean, JK. ; (2010) 'CTGF/CCN2 activates canonical Wnt signaling in mesangial cells through LRP6; implications for the pathogenesis of diabetic nephropathy'. European journal of biochemistry / FEBS, . [Details]
Brennan EP, Ehrich M, Brazil DP, Crean JK, Murphy M, Sadlier DM, Martin F,Godson C, McKnight AJ, van den Boom D, Maxwell AP, Savage DA. ; (2009) 'Comparative analysis of DNA methylation profiles in peripheral blood leukocytes versus lymphoblastoid cell lines'. Epigenetics : official journal of the DNA Methylation Society, 1 (4). [Details]
Godson C, Murphy M, Crean J, Brazil DP, Sadlier D, Martin F, ; (2008) 'Regulation and consequences of differential gene expression in diabetic kidney disease'. Biochemical Society Transactions, Pt 5 (NA):941-945. [DOI] [Details]
Furlong, F,Crean, J,Thornton, L,O'Leary, R,Murphy, M,Martin, F; (2007) 'Dysregulated intracellular signaling impairs CTGF-stimulated responses in human mesangial cells exposed to high extracellular glucose'. American Journal of Physiology - Renal Physiology, 292 :1691-1700. [DOI] [Details]
Mitchell, DM., Gaffney, A., Crean, JK., Kinsella, BT. and Godson C; (2007) 'The lipoxin A4 receptor is coupled to SHP-2 activation; implications for regulating growth factor receptor signalling'. Journal of Biological Chemistry, . [Details]
Reville, K; Crean, JK; Vivers, S; Dransfield, I; Godson, C; ; (2006) 'Lipoxin A(4) redistributes myosin IIA and Cdc42 in macrophages: Implications for phagocytosis of apoptotic leukocytes'. Immunology, 176 (3):1878-1888. [Details]
Crean, J.K., Furlong, F., Mitchell, D., McArdle E., Godson, C. and Martin, F.; (2006) 'Connective Tissue Growth Factor [CTGF]/CCN2 stimulates actin disassembly through Akt/protein kinase B (PKB) mediated phosphorylation and cytoplasmic translocation of p27Kip-1'. FASEB JOURNAL, 20 :1712-1714. [Details]
Kirwan, RP,Fenerty, CH,Crean, J,Wordinger, RJ,Clark, AF,O'Brien, CJ; (2005) 'Influence of cyclical mechanical strain on extracellular matrix gene expression in human lamina cribrosa cells in vitro'. Molecular Vision, 11 :798-810. [Details]
Ho, SL; Dogar, GF; Wang, J; Crean, J; Wu, QD; Oliver, N; Weitz, S; Murray, A; Cleary, PE; O'Brien, C; ; (2005) 'Elevated aqueous humour tissue inhibitor of matrix metalloproteinase-1 and connective tissue growth factor in pseudoexfoliation syndrome'. British Journal of Ophthalmology, 89 (2):169-173. [Details]
Crean, J. K.,Furlong, F.,Finlay, D.,Mitchell, D.,Murphy, M.,Conway, B.,Brady, H. R.,Godson, C.,Martin, F.; (2004) 'Connective tissue growth factor [CTGF]/CCN2 stimulates mesangial cell migration through integrated dissolution of focal adhesion complexes and activation of cell polarization'. Faseb J, 18 (13):1541-3. [Details]
Crean JK, Furlong F, Finlay D, Mitchell D, Conway B, Brady HR, Godson C, Martin F.; (2004) 'Connective tissue growth factor [CTGF]/CCN2 stimulates mesangial cell migration through integrated dissolution of focal adhesion complexes and activation of cell polarization'. FASEB JOURNAL, 18 . [Details]
Kirwan, RP; Crean, JK; Fenerty, CH; Clark, AF; O'Brien, CJ; ; (2004) 'Effect of cyclical mechanical stretch and exogenous transforming growth factor-beta 1 on matrix metalloproteinase-2 activity in lamina cribrosa cells from the human optic nerve head'. Journal of Glaucoma, 13 (4):327-334. [Details]
Kirwan, RP; Crean, JK; Clark, A; O'Brien, CJ; ; (2004) 'The effect of transforming growth factor beta-1 (TGF-beta 1) on gene expression profiles in lamina cribrosa cells from the human optic nerve head'. Investigative Ophthalmology Visual Science, 45 (NA):408-408. [Details]
Crean, J; Finlay, B; Conway, B; Murphy, M; Godson, G; Brady, HR; Finian, M; ; (2003) 'CCN-2 (CTGF) induces actin rearrangement and mesangial cell motility: Involvement of RhoA and protein kinase C zeta'. Journal of the American Society of Nephrology : JASN, 14 (NA):129-129. [Details]
Kirwan, RP; Crean, JK; Fenerty, C; Clark, AF; O'Brien, CJ; ; (2003) 'Differential gene expression in normal primary human lamina cribrosa cells exposed to cyclical mechanical stretch: A model for glaucomatous optic neuropathy'. Investigative Ophthalmology Visual Science, 44 (NA):295-295. [Details]
Ho, S; Crean, J; Oliver, N; Klaus, S; O'Brien, C; ; (2003) 'Elevated aqueous humour tissue inhibitor of matrix metalloproteinase-1 and connective tissue growth factor in pseudoexfoliation syndrome'. Investigative Ophthalmology Visual Science, 44 (NA):519-519. [Details]
Crean, J. K.,Finlay, D.,Murphy, M.,Moss, C.,Godson, C.,Martin, F.,Brady, H. R.; (2002) 'The role of p42/44 MAPK and protein kinase B in connective tissue growth factor induced extracellular matrix protein production, cell migration, and actin cytoskeletal rearrangement in human mesangial cells'. J Biol Chem, 277 (46):44187-94. [Details]
Crean JK, Finlay D, Murphy M, Moss C, Godson C, Martin F, Brady HR; (2002) 'The role of p42/44 MAPK and protein kinase B in connective tissue growth factor induced extracellular matrix protein production, cell migration, and actin cytoskeletal rearrangement in human mesangial cells'. Journal of Biological Chemistry, 27 (46):44187-44194. [Details]
O'Brien, CJ; Fenerty, CH; Crean, JKG; Clark, AF; ; (2001) 'Production of matrix metalloprotease-2 by glauomatous and non-glaucomatous optic nerve astrocytes'. Investigative Ophthalmology Visual Science, 42 (4):511-511. [Details]
Crean JK, Lappin D, Godson C, Brady HR; (2001) 'Connective tissue growth factor: an attractive therapeutic target in fibrotic renal disease'. Expert Opinion on Therapeutic Targets, 5 (4):519-530. [Details]
Devlin, HC; Crean, J; Fenerty, C; Clark, AF; O'Brien, C; ; (2001) 'Effects of mechanical stretch on the expression of MMPs and TIMPs by trabecular meshwork cells'. Investigative Ophthalmology Visual Science, 42 (4):140-140. [Details]
Crean JK, Duance VC, Sims TJ, Avery N, Smith S, Menage J, Eisenstein SM, Roberts S.; (1998) 'Changes in collagen cross-linking in degenerative disc disease and scoliosis'. Spine, 23 (23):2545-2551. [Details]
Crean JK, Roberts S, Eisenstein S and Duance V C; (1997) 'Matrix metalloproteinases in the human intervertebral disc: role in disc degeneration and scoliosis'. Spine, 22 (24):2877-2884. [Details]
Crean JK, Roberts S, Eisenstein S and Duance V C; (1995) 'Matrix metalloproteinase levels in diseased human intervertebral disc'. Journal of Bone Joint Surgery, 3 :260-263. [Details]

Other Journals

Crean JK, Roberts S, Eisenstein SM and Duance VC; (1995) 'Matrix metalloproteinase levels in diseased human intervertebral disc' Arthritis and Rheumatism Research Communications(Lumbar Spine Disorders) 10 :38-40. [Details]

Conference Publications

Andrews D, Browne J, O'Donovan H, Faherty N, Oliver N, Wallace D, O'Brien C and Crean J. (2012) Integrated signalling between CTGF and TGFβ2 leads to divergent activation of canonical and non-canonical pathways controlling EMT in ARPE-19 cells: Implications for the pathogenesis of proliferative vitreoretinopathy ARVO [Details]
Kavanagh, D., Gaffney A., Murphy, M., Faherty, N., Andrews, D., Higgins, D., McKay, G., Maxwell, P., Godson, C. and Crean, J. (2012) Wnt 6 is increased in diabetic nephropathy and modulates de novo tubulogenesis and opposes TGFbeta mediated epithelial cell differentiation in vitro American Society of Nephrology [Details]
Faherty N, Curran SP, O'Donovan H, Martin F, Godson C, Brazil DP, and Crean J. (2011) CCN2/CTGF increases expression of miR-302 microRNAs, which target the TGFβ type II receptor with implications for nephropathic cell phenotypes American Society of Nephrology [Details]
Rooney B, Gaffney, A., Godson, C., Sadlier, D and Crean, JK.; (2010) CTGF/CCN2 activates canonical Wnt signaling in mesangial cells through LRP6; implications for the pathogenesis of diabetic nephropathy American Society of Nephrology [Details]
Browne, M., Faherty, N.1, Xu, L., Oliver, N., Brazil, D. , Godson, C. and Crean, J. ; (2010) Connective Tissue Growth Factor (CTGF) causes Cdc42 activation and altered actin binding protein expression in the glomerular podocyte American Society of Nephrology [Details]
O'Donovan, H. 1, Xu, L.3, Oliver, N.3, Godson, C.2, and Crean, JK; (2010) CTGF/CCN2 and TGFBeta Superfamily signalling: Implications for therapeutic intervention American Society of Nephrology [Details]
Murphy, M,Crean, J,Brazil, DP,Saidlier, D,Martin, F,Godson, C (2008) BIOCHEMICAL SOCIETY TRANSACTIONS Regulation and consequences of differential gene expression in diabetic kidney disease , pp.941-945 [DOI] [Details]
Godson C, Murphy M, Crean J, Brazil DP, Sadlier D, Martin F, ; (2008) Biochemical Society transactions Regulation and consequences of differential gene expression in diabetic kidney disease , pp.941-945 [DOI] [Details]
Gaffney, A.*, Oliver, N.#, Godson, C.* and Crean, JK. (2007) FG3019 modulates CTGF-mediated mesangial cell adhesion and cytoskeletal signaling: implications for anti-CTGF directed therapeutic intervention American Society of Nephrology [Details]
Browne, M, Gaffney, A.*, O¿Leary, R., Furlong, F. *, Browne, J. *, Godson, C*., Martin, F. and Crean, JK (2007) A targeted cDNA microarray identifies cytoskeletal regulatory proteins as transcriptional targets of Connective Tissue Growth Factor (CTGF)/CCN2: Implications for diabetic nephropathy American Society of Nephrology [Details]
Crean, JK., Gaffney, A*., O¿Leary, R., Brown, P., Browne J., Devine, C., Martin, F. (2006) A targeted cDNA microarray identifies cytoskeletal regulatory proteins as transcriptional targets of Connective Tissue Growth Factor (CTGF)/CCN2: Implications for diabetic nephropathy American Society of Cell Biology [Details]
Fiona Furlong, John Crean, Laura Thornton, Ronan O¿Leary, Madeline Murphy, and Finian Martin (2005) Constitutive Phosphorylation of GSK3 by High Extracellular Glucose Impairs CTGF Stimulated Cell Migration in Human Mesangial Cells American Society of Cell Biology [Details]
Crean J, Finlay B, Conway B, Murphy M, Godson G, Brady HR, Martin, F (2003) CCN-2 (CTGF) induces actin rearrangement and mesangial cell motility: Involvement of RhoA and protein kinase C zeta American Society of Nephrology [Details]
Kirwan RP, Crean JK, Fenerty C, Clark AF, O'Brien.C (2003) Differential gene expression in normal primary human lamina cribrosa cells exposed to cyclical mechanical stretch: A model for glaucomatous optic neuropathy ARVO - The Association for Research in Vision and Ophthalmology [Details]
Ho S, Crean J, Oliver N, Klaus S, O'Brien C. (2003) Elevated aqueous humour tissue inhibitor of matrix metalloproteinase-1 and connective tissue growth factor in pseudoexfoliation syndrome ARVO [Details]
Crean JK, Finlay D, Martin F, Godson C, Brady HR (2002) The role of p42/44 MAPK and protein kinase B in connective tissue growth factor induced extracellular matrix protein production, cell migration and actin cytoskeletal rearrangement in human mesangial cells American Society of Nephrology [Details]
Crean JK, Finlay D, Godson C, Martin F, Brady HR (2002) Connective Tissue Growth Factor induces adhesion, contraction and cytoskeletal rearrangement in human mesangial cells: the role of Erk and Rho Kinases FASEB [Details]
Devlin HC, Crean J, Fenerty C, Clark AF, O'Brien C. (2001) Effects of mechanical stretch on the expression of MMPs and TIMPs by trabecular meshwork cells ARVO [Details]
O'Brien CJ, Fenerty CH, Crean J, Clark AF (2001) Production of matrix metalloprotease-2 by glauomatous and non-glaucomatous optic nerve astrocytes ARVO [Details]
         

Dissertations/Theses

Crean, J.K.,; (1998) The Collagenous Matrix of the Intervertebral Disc in Idiopathic Scoliosis and Other Degenerate Pathologies. Dissertations/Theses [Details]
Crean, J.K.,; (1993) Clot Lysis in the Upper Gastrointestinal Tract. Dissertations/Theses [Details]
           

Abstract

Crean, J,Finlay, B,Conway, B,Murphy, M,Godson, G,Brady, HR,Finian, M (2003) CCN-2 (CTGF) induces actin rearrangement and mesangial cell motility: Involvement of RhoA and protein kinase C zeta. Abstract [Details]
Ho, S,Crean, J,Oliver, N,Klaus, S,O'Brien, C (2003) Elevated aqueous humour tissue inhibitor of matrix metalloproteinase-1 and connective tissue growth factor in pseudoexfoliation syndrome. Abstract [Details]
Devlin, HC,Crean, J,Fenerty, C,Clark, AF,O'Brien, C (2001) Effects of mechanical stretch on the expression of MMPs and TIMPs by trabecular meshwork cells. Abstract [Details]
             

Presentation

Crean JK, Finlay B, Conway B, Murphy M, Godson G, Brady HR, Martin, F ; (2003) CCN-2 (CTGF) induces actin rearrangement and mesangial cell motility: Involvement of RhoA and protein kinase C zeta. Presentation [Details]
Kirwan RP, Crean JK, Fenerty C, Clark AF, O'Brien.C; (2003) Differential gene expression in normal primary human lamina cribrosa cells exposed to cyclical mechanical stretch: A model for glaucomatous optic neuropathy. Presentation [Details]
Ho S, Crean J, Oliver N, Klaus S, O'Brien C.; (2003) Elevated aqueous humour tissue inhibitor of matrix metalloproteinase-1 and connective tissue growth factor in pseudoexfoliation syndrome. Presentation [Details]
Crean JK, Finlay D, Martin F, Godson C, Brady HR; (2002) The role of p42/44 MAPK and protein kinase B in connective tissue growth factor induced extracellular matrix protein production, cell migration and actin cytoskeletal rearrangement in human mesangial cells. Presentation [Details]
Crean JK, Finlay D, Godson C, Martin F, Brady HR; (2002) Connective Tissue Growth Factor induces adhesion, contraction and cytoskeletal rearrangement in human mesangial cells: the role of Erk and Rho Kinases. Presentation [Details]
Devlin HC, Crean J, Fenerty C, Clark AF, O'Brien C.; (2001) Effects of mechanical stretch on the expression of MMPs and TIMPs by trabecular meshwork cells. Presentation [Details]
O'Brien CJ, Fenerty CH, Crean JKG, Clark AF; (2001) Production of matrix metalloprotease-2 by glauomatous and non-glaucomatous optic nerve astrocytes. Presentation [Details]
Crean JK, Roberts S, Avery N, Sims T, Bailey AJ and Duance, VC; (1997) Structural and Functional implications of changes in collagen crosslinking in the human intervertebral disc. Presentation [Details]
Crean JK, Roberts S, Eisenstein SM and Duance VC.; (1996) Turnover of the connective tissue matrix in diseased intervertebral disc. Presentation [Details]
                                               

Research

Research Interests

Statement of Research Interests

Dr. Crean has been engaged in research in the general area of cell-matrix interactions since completing his PhD in 1998, firstly in the biotechnology industry and latterly in an academic setting. Dr. Crean was a recipient of a Dublin Molecular Medicine Fellowship in 2001, enabling a return to academia in the Department of Medicine, University College Dublin. In 2005 he was awarded a prestigious Career Development Award and in 2007 was appointed to the Faculty of Science in University College Dublin as a tenure-track Lecturer in Pharmacology. He was subsequently awarded tenure in 2009. During this time he has been in receipt of >2,500,000  in funding from agencies including the Irish Health Research Board, Irish Research Council and  Science Foundation Ireland among others. He has established himself as a world-leading expert on CCN proteins and has published extensively in this area. He first identified CTGF as a profibrotic mediator  upregulated in both in vivo and in vitro models of DN  and characterised the mechanism through which CTGF expression leads to matrix accumulation and cell migration. He also identified CTGF as a profibrotic mediator in other diseases. Among the notable outcomes from the SSH were a large number of actin binding and regulatory proteins. Follow-up studies used a focused cDNA array consisting of probe sets derived from the differentially regulated genes emerging from the SSH. CTGF stimulated the differential expression of a number of genes, of which the actin binding and regulatory protein cluster were prominent. Subsequent studies found that CTGF induced cell migration and dysregulation of the actin cytoskeleton, mediated by dephosphorylation of focal adhesion kinase and paxillin, loss of RhoA activity, activation of Cdc42, and phosphorylation of PKC-ζ and GSK-3β. He has also found that the myosin light chain kinase plays a key regulatory role in cell polarization. These observations suggest a mechanism wherein activity of members of the RhoGTPase family can be regulated by CTGF through PI 3-kinase mediated phosphorylation and translocation of p27, suggesting a genetic programme culminating in differential expression and activity of actin binding and regulatory proteins. Most recently, he has characterized the complex interaction between CTGF and TGFb identifying a mir302 regulatory loop. These studies have been published in leading journals including Journal of Biological Chemistry, The FASEB Journal, The Journal of Immunology, The Biochemical Journal and The Journal of Cell Science. Throughout this time, there has been a close collaborative link with Fibrogen Inc., culminating in the progression of the anti CTGF monoclonal antibody, FG-3019 into Stage II clinical trials for Diabetic Nephropathy. The rationale for anti CTGF directed therapeutics in fibrosis is well established; continuing efforts supported by this application and associated programmes are focused on more targeted strategies which can be better facilitated by a complete understanding of the relationship between the CTGF enriched fibrotic microenvironment and TGFb superfamily members.




Research Projects

Sponsor : Irish Research Council for Science Engineering and Technology (IRCSET)
Fibrogen Inc USA
Title : Modular signalling activities of the CTGF/CCN2 domain structure: Implications for therapeutic intervention
Start Date / End Date : 15-DEC-08 / 14-DEC-11
Sponsor : Science Foundation Ireland (SFI)
Title : Mechanism of action of connective tissue growth factor: towards therapeutics in diabetic nephropathy
Start Date / End Date : 01-SEP-07 / 29-FEB-12
Sponsor : Fibrogen Inc USA
Title : Studies on mechanism of action of CTGF
Start Date / End Date : 01-JAN-07 / 31-DEC-11
   

Collaborators

Internal Collaborators

Catherine Godson

Finian Martin

Breandan Kennedy

Colm O'Brien


External Collaborators

David Liu

Noelynn Oliver

Roel Goldschmeding

Volker Haase
 
David Flint

Jeff Wrana

Derek Brazil

Darren Finlay