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Researchers at UCD

Amanda McCann

Senior Lecturer

School Of Medicine
Conway Institute
Belfield
Dublin 4

Tel: +353 1 7166742
Email: amanda.mccann@ucd.ie

Biography


My research focuses on the mechanisms underlying Paclitaxel (Taxol®) chemoresistance for women presenting with epithelial ovarian cancer (EOC) and Triple Negative Breast Cancer (TNBC); specifically the spindle assembly checkpoint protein MAD2 through which Paclitaxel exerts its apoptotic affect. Epigenetically, the group are also interested in profiling DNA methylation and histone modification signatures in hypoxia and how this relates to ultimate chemoresistance and the retention of cellular viability (senescence/ autophagy) in the face of chemotherapeutic engagement.

 I am also Group coordinator of the UCD/Mater Hospital/St Vincent's University Hospital Triple Negative Breast Cancer (TNBC) Group. In addition, I am leading the submission of a proposal to the UCD authority for an Academic Centre in Translational Oncology. 


2004, 2002, 1997, 1993
Awarded a President's Research Award from UCD
1997-2005 College Lecturer, UCD
1993 Special Lecturer Department of Pathology UCD
1992 Awarded the Alton Gold Medal for Clinical Research Mater Hospital December
1992 PhD Biochemistry Department TCD and Mater Hospital Dublin

Professional

         

Conference Contributions

Greene, L. M., Twal, W. O., Donovan, N. O., McCann, A. H., Dervan, P. A., Duffy, M. J., Argraves, W. S., and Gallagher, W. M.; (2001) Proteolytic processing of fibulin-1 is linked with estrogen receptor status in human breast tumours and tumour-derived cell lines. [Oral Presentation], The Irish Association for Cancer Research/Irish Society of Medical Oncology Joint Cancer Research Meeting, Cork, Cork , 27-SEP-01 - 28-SEP-01.
 

Employment

Employer: UCD
Position: Senior Lecturer

Education

Year 1992 Institution: Trinity College Dublin
Qualification: PhD Subject:
         

Publications

     

Peer Reviewed Journals

Weiner-Gorzel K, Dempsey E, Milewska M, McGoldrick A, Toh V, Walsh A, Lindsay S, Gubbins L, Cannon A, Sharpe D, O'Sullivan J, Murphy M, Madden SF, Kell M, McCann A, Furlong F (2015) 'Overexpression of the microRNA miR-433 promotes resistance to paclitaxel through the induction of cellular senescence in ovarian cancer cells'. Cancer medicine, 4 (5):745-758. [DOI] Link to full text [Details]
Elma A. O¿Reilly, E. A.; Gubbins, L.; Sharmaa, S.; Tully, R.; Zhing Guang, M. H.; Weiner-Gorzel, K.; McCaffrey, J.; Harrison, M.; Furlong, F.; Malcolm Kell, M.; and McCann, A. (2015) 'The fate of chemoresistance in triple negative breast cancer (TNBC)'. BBA Clinical, 3 :257-275. [Details]
Joyce H, McCann A;Clynes M;Larkin A (2015) 'Influence of multidrug resistance and drug transport proteins on chemotherapy drug metabolism'. Expert Opinion on Drug Metabolism and Toxicology, 11 (5):795-809. [DOI] [Details]
McGrogan B, Phelan S, Fitzpatrick P, Maguire A, Prencipe M, Brennan D, Doyle E, O'Grady A, Kay E, Furlong F, McCann A. (2014) 'Spindle assembly checkpoint protein expression correlates with cellular proliferation and shorter time to recurrence in ovarian cancer'. Human Pathology, 45 (7):1509-1519. [DOI] [Details]
McElnea, E. M., Hughes, E., McGoldrick, A., McCann, A., Quill, B., Docherty, N., Irnaten, M., Farrell, M., Clark, A. F., O'Brien, C. J., Wallace, D. M. (2014) 'Lipofuscin accumulation and autophagy in glaucomatous human lamina cribrosa cells'. BMC Ophthalmology, 14 :153. Available Online [Details]
d'Adhemar CJ, Spillane CD, Gallagher MF, Bates M, Costello KM, Barry-O'Crowley J, Haley K, Kernan N, Murphy C, Smyth PC, O'Byrne K, Pennington S, Cooke AA, Ffrench B, Martin CM, O'Donnell D, Hennessy B, Stordal B, Finn S, McCann A, Gleeson N, D'Arcy T, Flood B, O'Neill LA, Sheils O, O'Toole S, O'Leary JJ (2014) 'The MyD88+ phenotype is an adverse prognostic factor in epithelial ovarian cancer'. PLoS ONE, 9 (6). [DOI] [Details]
Murphy TM, O'Donovan A, Mullins N, O'Farrelly C, McCann A, Malone K (2014) 'Anxiety is associated with higher levels of global DNA methylation and altered expression of epigenetic and interleukin-6 genes'. Psychiatric Genetics, . [DOI] [Details]
Watson, C.J. and Collier, P. and Tea, I. and Neary, R. and Watson, J.A. and Robinson, C. and Phelan, D. and Ledwidge, M.T. and Mcdonald, K.M. and Mccann, A. and Sharaf, O. and Baugh, J.A. (2014) 'Hypoxia-induced epigenetic modifications are associated with cardiac tissue fibrosis and the development of a myofibroblast-like phenotype'. Human Molecular Genetics, 23 (8):2176-2188. Available Online [DOI] [Details]
Zhou, ZM,McCann, A,Litrup, E,Murphy, R,Cormican, M,Fanning, S,Brown, D,Guttman, DS,Brisse, S,Achtman, M (2013) 'Neutral Genomic Microevolution of a Recently Emerged Pathogen, Salmonella enterica Serovar Agona'. PLoS Genetics, 9 . [DOI] [Details]
O Leary PC, Penny SA, Dolan RT, Kelly CM, Madden SF, Rexhepaj E, Brennan DJ, McCann AH, Pontén F, Uhlén M, Zagozdzon R, Duffy MJ, Kell MR, Jirström K, Gallagher WM (2013) 'Systematic antibody generation and validation via tissue microarray technology leading to identification of a novel protein prognostic panel in breast cancer'. BMC Cancer, 13 . [DOI] [Details]
Furlong F, Fitzpatrick P, Phelan S, Maguire A, McGrogan B, Prencipe M, McGoldrick A, McGettigan P, Brennan D, Gallagher M, Sharon O'Toole S, Sheils O, O'Grady A, Kay EW, O'Leary J, McCann A. (2012) 'Low MAD2 expression associates with reduced progression free survival in patients with serous papillary epithelial ovarian cancer'. Journal of Pathology, 226 (5):746-755. [Details]
Saldova R, McCann A;Rudd PM (2012) 'Commentary on paper: 5-Aza-2'-deoxycytidine increases sialyl Lewis X on MUC1 by stimulating ¿¿-galactoside:¿¿2,3-sialyltransferase 6 gene (Chachadi et al.)'. International Journal of Biochemistry and Cell Biology, 44 (5). [DOI] [Details]
Furlong, F,Fitzpatrick, P,O'Toole, S,Phelan, S,McGrogan, B,Maguire, A,O'Grady, A,Gallagher, M,Prencipe, M,McGoldrick, A,McGettigan, P,Brennan, D,Sheils, O,Martin, C,Kay, EW,O'Leary, J,McCann, A (2012) 'Low MAD2 expression levels associate with reduced progression-free survival in patients with high-grade serous epithelial ovarian cancer'. Pathology, 226 :746-755. [DOI] [Details]
Smith, JD,Meehan, MH,Crean, J,McCann, A; (2011) 'Alpha T-catenin (CTNNA3): a gene in the hand is worth two in the nest'. Cellular and Molecular Life Sciences, 68 :2493-2498. [DOI] [Details]
Radka Saldova, Eugene Dempsey, Marta Pérez-Garay, Karina Mariño, Jenny A Watson, Alfonso Blanco-Fernández, Weston B Struwe, David J Harvey, Stephen F Madden, Rosa Peracaula, Amanda McCann, Pauline M Rudd (2011) '5-AZA-2'-deoxycytidine induced demethylation influences N-glycosylation of secreted glycoproteins in ovarian cancer'. Epigenetics : official journal of the DNA Methylation Society, 6 (11):1362-1372. [DOI] [Details]
Doi T, Puri P, McCann A, Bannigan J, Thompson J; (2011) 'Epigenetic effect of cadmium on global de novo DNA hypomethylation in the cadmium-induced ventral body wall defect (VBWD) in the chick model'. Toxicological sciences : an official journal of the Society of Toxicology, 120 (2):475-480. [DOI] [Details]
Jin Y, Amaral A, McCann A, Brennan L; (2011) 'Homocysteine levels impact directly on epigenetic reprogramming in astrocytes'. Neurochemistry International, . [DOI] [Details]
Prencipe, M,McGoldrick, A,Perry, AS,O'Grady, A,Phelan, S,McGrogan, B,Fitzpatrick, P,Watson, JA,Furlong, F,Brennan, DJ,Lawler, M,Kay, E,McCann, A; (2010) 'MAD2 downregulation in hypoxia is independent of promoter hypermethylation'. Cell cycle (Georgetown, Tex.), 9 :2856-2865. [DOI] [Details]
Watson JA, Watson CJ, McCann A, Baugh J; (2010) 'Epigenetics, the epicenter of the hypoxic response'. Epigenetics : official journal of the DNA Methylation Society, 5 (4):293-296. [Details]
Watson, J. A.,Watson, C. J.,McCrohan, A. M.,Woodfine, K.,Tosetto, M.,McDaid, J.,Gallagher, E.,Betts, D.,Baugh, J.,O'Sullivan, J.,Murrell, A.,Watson, R. W.,McCann, A.; (2009) 'Generation of an epigenetic signature by chronic hypoxia in prostate cells'. Hum Mol Genet, 18 (1919):3594-6043594. Available Online [Details]
McCann A, Watson JA, Burling K, Fitzpatrick P, Kay E, Kelly J, Fitzpatrick JM, Dervan PA, ; (2009) 'Urinary insulin-like growth factor 2 identifies the presence of urothelial carcinoma of the bladder'. BJU International, 5 (NA):694-697. [DOI] [Details]
Prencipe M, Fitzpatrick P, Gorman S, Tosetto M, Klinger R, Furlong F, Harrison M, O'Connor D, Roninson IB, O'Sullivan J, McCann A; (2009) 'Cellular senescence induced by aberrant MAD2 levels impacts on paclitaxel responsiveness in vitro'. British Journal of Cancer, 101 (11):1900-1908. [DOI] [Details]
Gallagher, E. M.,O'Shea, D. M.,Fitzpatrick, P.,Harrison, M.,Gilmartin, B.,Watson, J. A.,Clarke, T.,Leonard, M. O.,McGoldrick, A.,Meehan, M.,Watson, C.,Furlong, F.,O'Kelly, P.,Fitzpatrick, J. M.,Dervan, P. A.,O'Grady, A.,Kay, E. W.,McCann, A.; (2008) 'Recurrence of urothelial carcinoma of the bladder: a role for insulin-like growth factor-II loss of imprinting and cytoplasmic E-cadherin immunolocalization'. Clin Cancer Res, 14 (21):6829-38. Available Online [Details]
McCann A, McGrogan BT, Gilmartin B, Carney DN, ; (2008) 'Taxanes, microtubules and chemoresistant breast cancer'. 1785 (2):96-132. [DOI] [Details]
Mc Cormack, O., Chung, W. Y., Fitzpatrick, P., Cooke, F., Flynn, B., Harrison, M., Fox, E., Gallagher, E., Mc Goldrick, A., Dervan, P. A., Mc Cann, A., Kerin, M. J., ; (2008) 'Growth arrest-specific gene 6 expression in human breast cancer'. British Journal of Cancer, 98 (6):1141-1146. [DOI] [Details]
Armstrong, ME,Gantier, M,Li, LL,Chung, WY,McCann, A,Baugh, JA,Donnelly, SC; (2008) 'Small interfering RNAs induce macrophage migration inhibitory factor production and proliferation in breast cancer cells via a double-stranded RNA-dependent protein kinase-dependent mechanism'. Journal of Immunology, 180 :7125-7133. [Details]
Mc Cormack O, Chung WY, Fitzpatrick P, Cooke F, Flynn B, Harrison M, Fox E,Gallagher E, McGoldrick A, Dervan PA, McCann A, Kerin MJ.; (2008) 'Progesterone receptor B (PRB) promoter hypermethylation in sporadic breast cancer: Progesterone receptor B hypermethylation in breast cancer'. Breast Cancer Research and Treatment, 111 :45-53. [Details]
Rexhepaj, E., Brennan, D. J., Holloway, P., Kay, E. W., McCann, A. H., Landberg, G., Duffy, M. J., Jirstrom, K., and Gallagher, W. M. ; (2008) 'Novel image analysis approach for quantifying expression of nuclear proteins assessed by immunohistochemistry: application to measurement of estrogen and progesterone receptor levels in breast cancer'. Breast cancer research : BCR, 10 (5):R89. [DOI] [Details]
Kerin MJ, Mc Cormack O, Chung WY, Fitzpatrick P, Cooke F, Flynn B, Harrison M, Fox E, Gallagher E, Goldrick AM, Dervan PA, Mc Cann A, ; (2008) 'Growth arrest-specific gene 6 expression in human breast cancer'. Journal of Cancer, 98 (6):1141-1146. [DOI] [Details]
Meehan, M.,Melvin, A.,Gallagher, E.,Smith, J.,McGoldrick, A.,Moss, C.,Goossens, S.,Harrison, M.,Kay, E.,Fitzpatrick, J.,Dervan, P.,Mc Cann, A.; (2007) 'Alpha-T-catenin (CTNNA3) displays tumour specific monoallelic expression in urothelial carcinoma of the bladder'. Genes Chromosomes Cancer, 46 (6):587-93. [Details]
Hosey, AM,Gorski, JJ,Murray, MM,Quinn, JE,Chung, WY,Stewart, GE,James, CR,Farragher, SM,Mulligan, JM,Scott, AN,Dervan, PA,Johnston, PG,Couch, FJ,Daly, PA,Kay, E,McCann, A,Mullan, PB,Harkin, DP; (2007) 'Molecular basis for estrogen receptor alpha deficiency in BRCA1-linked breast cancer'. Journal of the National Cancer Institute, 99 :1683-1694. [DOI] [Details]
O'Sullivan, FM,Murphy, SK,Simel, LR,McCann, A,Callanan, JJ,Nolan, CM; (2007) 'Imprinted expression of the canine IGF2R, in the absence of an anti-sense transcript or promoter methylation'. Evolution and Development, 9 :579-589. [Details]
Mc Cormack O, Chung WY, Fitzpatrick P, Cooke F , Flynn B , Harrison M, Fox E, Gallagher E, Mc Goldrick A, Dervan PA, McCann A, Kerin MJ; (2007) 'Progesterone Receptor B (PRB) promoter hypermethylation in sporadic breast cancer'. Breast Cancer Research and Treatment, . [Details]
O'Brien SL, Fagan A, Fox EJ, Millikan RC, Culhane AC, Brennan DJ, McCann AH,; (2007) 'CENP-F expression is associated with poor prognosis and chromosomal instability in patients with primary breast cancer'. International Journal of Cancer, 120 (7):1434-1443. [Details]
Gallagher, E,Goldrick, AM,Chung, WY,Cormack, OM,Harrison, M,Kerin, M,Dervan, PA,Cann, AM; (2006) 'Gain of imprinting of SLC22A18 sense and antisense transcripts in human breast cancer'. GENOMICS, 88 (1):12-17. [DOI] [Details]
Carder, PJ; Murphy, CE; Dervan, P; Kennedy, M; McCann, A; Saunders, PTK; Shaaban, AM; Foster, CS; Witton, CJ; Bartlett, JMS; Walker, RA; Speirs, V; ; (2005) 'A multi-centre investigation towards reaching a consensus on the immunohistochemical detection of ER beta in archival formalin-fixed paraffin embedded human breast tissue'. Breast Cancer Research and Treatment, 92 (3):287-293. [Details]
Balfe P, McCann A, McGoldrick A, McAllister K, Kennedy M, Dervan P, Kerin MJ.; (2004) 'Estrogen receptor alpha and beta profiling in human breast cancer'. European Journal of Surgical Oncology, 30 (5):469-474. [Details]
Mc Cormack, OM; Mc Cann, AH; Chung, WY; Cooke, F; Flynn, B; Gallagher, E; Mc Goldrick, A; Welch, HM; Dervan, PA; Kerin, MJ; ; (2004) 'Progesterone receptor B promoter hypermethylation in breast carcinoma; correlation with mRNA and protein levels'. Breast Cancer Research and Treatment, 88 (NA):176-176. [Details]
Shahbazi, RI; McCann, A; Frawley, A; Doran, P; Chung, WY; Dervan, P; Kerin, MJ; ; (2004) 'Validation of gamma-actin as a potential target in breast cancer'. British Journal of Surgery, 91 (9):1216-1216. [Details]
Balfe, P; McCann, A; McGoldrick, A; Kennedy, M; McAllister, K; Dervan, P; Kerin, MJ; ; (2003) 'Antiestrogen therapy could be harmful in patients with oestrogen receptor-beta dominant tumours'. British Journal of Surgery, 90 (NA):102-103. [Details]
Cooke, FJ; McCann, AH; Balfe, P; McAlister, K; Kennedy, M; Dervan, P; Kerin, MJ; ; (2003) 'Epigenetic control of the oestrogen receptor genes in breast cancer'. British Journal of Surgery, 90 (NA):42-43. [Details]
Greene, LM, Twal, WO, Duffy, MJ, McDermott, EW, Hill, AD, O'Higgins, NJ, McCann, A, Dervan, P, Argraves, W, Gallagher, WM, ; (2003) 'Elevated expression and altered processing of fibulin-1 protein in human breast cancer'. British Journal of Cancer, 88 (6):871-878. [Details]
Cooke, FJ; Balfe, P; McCann, AH; Dervan, P; Kennedy, M; Kerin, M; ; (2002) 'An investigation into the methylation status of oestrogen receptor beta and its subsequent expression in human breast cancer'. European Journal of Human Genetics, 10 (NA):83-84. [Details]
McGoldrick, A; McCann, A; Fitzpatrick, J; Smith, J; Dervan, PA; ; (2002) 'Has bladder cancer MET its maker?'. Pathology, 198 (NA):41-41. [Details]
McGoldrick, A; McCann, A; Fitzpatrick, J; Smith, J; Dervan, PA; ; (2002) 'Microarray generated oncogene copy number profiling in human bladder cancer'. British Journal of Cancer, 86 (NA):23-23. [Details]
Pedersen, IS; Dervan, P; McGoldrick, A; Harrison, M; Ponchel, F; Speirs, V; Isaacs, JD; Gorey, T; McCann, A; ; (2002) 'Promoter switch: a novel mechanism causing biallelic PEG1/MEST expression in invasive breast cancer'. Human Molecular Genetics, 11 (12):1449-1453. [Details]
Fabre, A,McCann, AH,O'Shea, D,Broderick, D,Keating, G,Tobin, B,Gorey, T,Dervan, PA; (1999) 'Loss of heterozygosity of the Wilms' tumor suppressor gene (WT1) in in situ and invasive breast carcinoma'. Human Pathology, 30 :661-665. [Details]
Pedersen, I.S., Dervan, P.A., Broderick, D., Harrison, M., Miller, N., Delany, E., O'Shea, D., Costello, P., McGoldrick, A., Keating, G., Tobin, B., Gorey, T., and McCann, A.; (1999) 'Frequent loss of imprinting of PEG1/MEST in invasive breast cancer'. Cancer Research, 59 (21):5449-5451. [Details]
Costello, PJ; McCann, AH; Gorey, T; Dervan, PA; ; (1999) 'Some non high grade ductal carcinomas in situ are polyclonal'. Laboratory Investigation, 79 (1):17-17. [Details]
Miller, N; McCann, A; O'Connell, D; Pedersen, IS; Spiers, V; Gorey, T; Dervan, PA; ; (1998) 'Mono-allelic expression of the Mas proto-oncogene in human breast tissue'. European Journal of Human Genetics, 6 (NA):147-147. [Details]
McGarry, Y; Lewis, S; McCann, A; Moran, E; Sinha, SK; Kelehan, P; Dervan, P; ; (1998) 'Distribution of the antigen recognised by the monoclonal antibody P1H10 in ovarian and breast tissue'. British Journal of Cancer, 78 (NA):68-68. [Details]
Costello, P; McCann, AH; Moore, E; Gorey, T; Dervan, PA; ; (1998) 'Clonal analysis of breast DCIS on microdissected tumour cells using differential methylation of HUMARA (Xq12)'. LABORATORY INVESTIGATION, 78 (1):18-18. [Details]
Miller, N,McCann, AH,O'Connell, D,Pedersen, IS,Spiers, V,Gorey, T,Dervan, PA; (1997) 'The MAS proto-oncogene is imprinted in human breast tissue'. Genomics, 46 :509-512. [Details]
McCann AH, Miller N, O'Meara A, Pedersen I, Keogh K, Gorey T, Dervan PA; (1996) 'Biallelic expression of the IGF2 gene in human breast disease'. Human Molecular Genetics, 5 (8):1123-1127. [Details]
MCCANN, AH; KIRLEY, A; CARNEY, DN; CORBALLY, N; MAGEE, HM; KEATING, G; DERVAN, PA; ; (1995) 'AMPLIFICATION OF THE MDM2 GENE IN HUMAN BREAST-CANCER AND ITS ASSOCIATION WITH MDM2 AND P53 PROTEIN STATUS'. British Journal of Cancer, 71 (5):981-985. [Details]
Costello P, McCann A, Carney DN, Dervan PA.; (1995) 'Prognostic Significance of Microvessel density in lymph node negative breast carcinoma'. Human Pathology, 26 (11):1181-1184. [Details]
McCann, A.H., Dervan, P.A., O'Regan, M., Codd, M.B., Gullick, W.J., Tobin, B.M., and Carney, D.N.; (1991) 'Prognostic significance of c-erbB-2 and estrogen receptor status in human breast cancer'. Cancer Research, 51 (12):3296-3303. [Details]
 

Conference Publications

Ivers, L; Cummings, BK; McCann, A; Itasaki, N (2013) The effect of microenvironment on breast cancer cells cultured in 3D matrix Irish Association for Cancer Research Annual Meeting [Details]
Brennan, D.J., Hewitt, S.M., Fox, E.J.P., O'Brien, S., Jirstrom, K., Duffy, M.J., Landberg, G., McCann, A. & Gallagher, W.M.; (2006) Automated quantitative analysis of immunohistochemistry linked to clinical outcome Automated quantitative analysis of immunohistochemistry linked to clinical outcome Dublin, Ireland, [Details]
   

Editorial

Saldova, R,McCann, A,Rudd, PM (2012) Commentary on paper: 5-Aza-2 '-deoxycytidine increases sialyl Lewis X on MUC1 by stimulating beta-galactoside:alpha 2,3-sialyltransferase 6 gene (Chachadi et al.). Editorial [DOI] [Details]
Chai, K,Kitamura, K,McCann, A,Wu, XR (2010) The Epithelium-Molecular Landscaping for an Interactive Barrier. Editorial [DOI] [Details]
                 

Abstract

McEvoy, L,O'Toole, S,Spillane, C,Stordal, B,Gallagher, M,Martin, C,Norris, L,Gleeson, N,McGoldrick, A,Furlong, F,McCann, A,Sheils, O,O'Leary, J (2013) Novel Hypoxia-Associated Markers of Chemoresistance in Ovarian Cancer. Abstract [Details]
McEvoy, L,O'Toole, S,Spillane, C,Stordal, B,Gallagher, M,Martin, C,Norris, L,Gleeson, N,McGoldrick, A,Furlong, F,McCann, A,Sheils, O,O'Leary, J (2013) Novel Hypoxia-Associated Markers of Chemoresistance in Ovarian Cancer. Abstract [Details]
O'Reilly, EA,Furlong, F,Salman, R,Bambury, R,Harrison, M,Drew, G,Kelly, C,O'Grady, A,Kay, E,McCann, A,Kell, M (2012) Senescent and Autophagic cellular fates predict chemoresponse in TNBC. Abstract [Details]
Weiner-Gorzel, K,O'Reilly, E,McGoldrick, A,Fitzpatrick, P,O'Toole, S,Maguire, A,Kay, E,O'Leary, J,McCann, A,Furlong, F (2012) Mitotic Arrest Deficiency Protein 2 (MAD2) and Histone Deacetylase 6 (HDAC6) Present a Complex Relationship in Their Regulation and Expression and Subsequent Impact on Chemoresponsiveness. Abstract [Details]
Hazel, K,Toh, V,McGoldrick, A,McCann, A,Furlong, F (2011) COMPARATIVE MAD2 EXPRESSION AND CHEMOSENSITIVITY ANALYSES IN EPITHELIAL OVARIAN CANCER (EOC) IN VITRO. Abstract [Details]
Toh, V,Hazel, K,McCann, A,Furlong, F (2011) THE FATE OF CHEMORESISTANCE IN EPITHELIAL OVARIAN CARCINOMA (EOC). Abstract [Details]
Furlong, F,Prencipe, M,McGoldrick, A,McGettigan, P,Carney, D,Doyle, E,Kay, F,McCann, A (2010) miR-433 overexpression attenuates the spindle assembly checkpoint response to paclitaxel. Abstract [DOI] [Details]
Woods, G,McCann, A,Phelan, S (2010) MEMBRANOUS STAINING OF THE KEY ADHERENS JUNCTIONAL (AJ) PROTEIN ALPHAT-CATENIN (CTNNA3) IS COMPROMISED IN HUMAN BREAST CANCER. Abstract [Details]
Smith, JD,Meehan, M,McGoldrick, A,Harrison, M,McCormack, O,Dervan, P,Fitzpatrick, J,Kerin, M,McCann, A (2007) Alpha-T-catenin, a novel gene involved in cell adhesion, is structurally and epigenetically altered in breast cancer and not in lymph node deposits. Abstract [Details]
Mccann, A,O'Shea, DM,Fitzpatrick, P,O'Grady, A,Harrison, M,O'Kelly, P,Gilmartin, B,Watson, C,Beasley, A,Fitzpatrick, JM,Dervan, PA,Kay, EW (2007) Cytoplasmic E-cadherin (cdh1) staining is an independent predictor of time to recurrence in bladder cancer. Abstract [Details]
Clarke, T,Jenny, O,Fitzpatrick, JM,McCann, A (2007) Transcriptional regulation of E-cadherin (CDH1) in urothelial carcinoma of the bladder - the key players. Abstract [Details]
Shahbazi, RI,McCann, A,Frawley, A,Doran, P,Chung, WY,Dervan, P,Kerin, MJ (2004) Validation of gamma-actin as a potential target in breast cancer. Abstract [Details]
Balfe, P,McCann, A,McGoldrick, A,Kennedy, M,McAllister, K,Dervan, P,Kerin, MJ (2003) Antiestrogen therapy could be harmful in patients with oestrogen receptor-beta dominant tumours. Abstract [Details]
McGoldrick, A,McCann, A,Fitzpatrick, J,Smith, J,Dervan, PA (2002) Has bladder cancer MET its maker?. Abstract [Details]
McGoldrick, A,McCann, A,Fitzpatrick, J,Smith, J,Dervan, PA (2002) Microarray generated oncogene copy number profiling in human bladder cancer. Abstract [Details]
Greene, L. M., Twal, W. O., Maguire, T., McCann, A., Dervan, P., Duffy, M. J., Argraves, W. S., and Gallagher, W. M.; (2001) Proteolytic processing of fibulin-1 in human breast tumors is linked with estrogen receptor status. Abstract [Details]
Miller, N,McCann, A,O'Connell, D,Pedersen, IS,Spiers, V,Gorey, T,Dervan, PA (1998) Mono-allelic expression of the Mas proto-oncogene in human breast tissue. Abstract [Details]
McGarry, Y,Lewis, S,McCann, A,Moran, E,Sinha, SK,Kelehan, P,Dervan, P (1998) Distribution of the antigen recognised by the monoclonal antibody P1H10 in ovarian and breast tissue. Abstract [Details]
       

Reviews

McGrogan, BT,Gilmartin, B,Camey, DN,McCann, A (2008) Taxanes, microtubules and chemoresistant breast cancer. Reviews [DOI] [Details]
                                                   

Letters

Hosey, AM,Gorski, JJ,Quinn, JE,Chung, WY,Mccann, A,Harkin, DP (2008) Re: Molecular basis for estrogen receptor alpha deficiency in BRCA1-linked breast cancer - Response. Letters [DOI] [Details]

Research

Research Interests

My group's specific area of interest is to decipher how cancer cells can maintain viability via cellular senescence in the face of chemotherapy,  particularly in the space of triple negative breast cancer and high grade serous ovarian cancer. Cellular senescence is a viable cellular fate mechanism which although non-replicative, is highly metabolically active producing a wealth of cytokines and an increased release of exosomes that  impact directly on the tumour microenvironment.  Tumour hypoxia integral to chemoresistance and indeed chemotherapeutic agents such as the taxanes and platinums used in the portfolio of drugs in the TNBC and ovarian cancer setting can also induce senescence.  We and others believe that the eradication of senescent cells will ensure a more efficacious patient response to chemotherapy.   

  • Breast Cancer
  • Bladder Cancer
  • Genomic Imprinting
  • DNA Methylation/Histone Acetylation
  • Microarray CGH

Identification Of EMT Related Markers As Indicators Of TCC Bladder Cancer

Recurrence Transitional cell carcinoma of the bladder (TCCB) inherently has a high risk of tumour recurrence associated with its biology.  Importantly, no reliable molecular marker is currently available to identify which TCCB patients are likely to develop metastatic disease.  In the scientific literature, there is much interest in the phenomenon of epithelial mesenchymal transition (EMT).  This describes the conversion from an epithelial to a mesenchymal phenotype, and is increasingly being considered as an important event in carcinoma progression and metastasis.  The increased invasive potential associated with EMT, coincides with loss of epithelial characteristics, and the acquisition of cells with an increased migratory and motile phenotype, allowing them to detach away from the parent tumour and move to distant sites.  As part of this EMT process, a number of proteins have been found to play a key role, identifying them therefore as candidate predictors of metastasis.  Little is known however about these proteins in TCC of the bladder.  Our overall hypothesis is that detection of EMT, either in the bladder tissue at the time of diagnosis, or in the patients¿ urine in subsequent follow up, will accurately predict the likelihood of bladder tumour recurrence, and thereby indicate the need for closer patient monitoring.  The development of an EMT urine test could result in an accurate non-invasive procedure to monitor TCC disease progression. 


Resistance To Microtubule Inhibitor (MI) Chemotherapy In Human Breast Cancer


In the advanced /metastatic breast cancer setting, there has been increased clinical use of microtubule inhibitors (MIs) such as Taxol® (paclitaxel), Taxotere® (docetaxel) and newer MIs such as Panzem® (2-ME2( 2-methoxyestradiol) in combinational chemotherapeutic regimes. 
However, breast cancer patients often have de novo resistance, or incomplete response to these MIs, even considering the fact that these agents constitute some of the most active agents for patients with this malignancy.  The mechanisms underlying this MI chemoresistance are currently unknown. 

In an effort to try and understand why certain breast tumours are refractory to these agents, we have undertaken a comprehensive analysis of two key effector molecules of the mitotic spindle assembly checkpoint MSC system, namely hsMAD1 and hsMAD2.  Our reasoning for investigating these molecules is as follows.  Microtubule inhibitors exert their affects on cellular mitosis through this spindle checkpoint MSC system.  This system is one of the main surveillance mechanisms censoring microtubule damage, the functionality of which hinges on the competency of hsMAD1 and hsMAD2.  When functioning properly, the MSC system ensures that the damage exerted on the microtubules by MIs is monitored, and therefore inhibits cells in proceeding to mitosis.  However, when the surveillance system is compromised, microtubule damage goes unchecked, and cells inappropriately complete the cell cycle.  It is therefore our hypothesis, that MAD1/MAD2 functionality is a prime candidate to help in identifying the sensitivity of breast cancer tumours to MI based chemotherapeutic regimes.  These are novel concepts and investigations for this tumour. 

Research Projects

Sponsor : Health Research Board (HRB)
Title : Putting the positivity back into triple negative breast cancer chemo-responsiveness
Start Date / End Date : 01-OCT-11 / 30-SEP-15
Sponsor : The Mater Foundation
Title : The anti-IL6 antibody siltuximab, enhances the efficacy of Paclitaxel (Taxol®) in Triple Negative Breast Cancer Cells (TNBCs) by inhibiting the induction of viable chemoresistant senescent cells.
Start Date / End Date : 30-OCT-12 / 30-OCT-13
Sponsor : The Mater Foundation
Title : Exosome-mediated transfer of senescence signals in the tumour microenvironment (TME): A mechanism for propagating survival in the face of chemotherapy.
Start Date / End Date : 01-JUL-13 / 11-APR-16
Sponsor : Health Research Board (HRB)
Title : Preventing chemotherapy resistance in triple negative breast cancer
Start Date / End Date : 01-OCT-14 / 30-SEP-17
Sponsor : The Mater Foundation
Title : EXOSOME-MEDIATED TRANSFER OF SENESCENCE SIGNALS IN THE TUMOUR MICROENVIRONMENT (TME): A MECHANISM FOR PROPAGAING SURVIVAL IN THE FACE OF CHEMOTHERAPY
Start Date / End Date : 01-JUL-14 / 01-JUL-15
Sponsor : The Mater Foundation
Title : Inhibition of the exosomal marker TSG101 (Tumour Susceptibility Gene 101) enhances the cellular response of Triple Negative Breast Cancer (TNBC) cells to Paclitaxel (Taxol)
Start Date / End Date : 01-JUL-14 / 01-JUL-15
Sponsor : Irish Research Council (IRC)
Title : Breast Surgery Recovery: The Clinical and Social Impact of the IsisRose Post Surgery Bra
Start Date / End Date : 01-MAR-15 / 28-FEB-17
Sponsor : University College Dublin (UCD)
Title : School funded research accounts - Amanda McCann
Start Date / End Date : 01-JUN-15 / 30-SEP-18
Sponsor : Health Research Board (HRB)
Title : Is the presence of neonatal cytomegalovirus specific IgM a useful diagnostic predictor of childhood sensorineural hearing loss?
Start Date / End Date : 04-JUN-12 / 27-JUL-12
Sponsor : University College Dublin Foundation Ltd.
Title : The Fate of Chemoresistance in Triple Negative Breast Cancer (TNBC)
Start Date / End Date : 11-JUL-11 / 11-JUL-13
Sponsor : Pathological Society of Great Britain and Ireland
Title : Identifying a Spindle Assembly Checkpoint Signature Predictive of Paclitaxel Resistance in Ovarian Cancer
Start Date / End Date : 01-JAN-09 / 31-DEC-09
Sponsor : Mater College for Postgraduate Education & Research
Title : Investigation into the epigenetic regulation of E-cadherin in breast cancer
Start Date / End Date : 01-JAN-09 / 31-DEC-09
Sponsor : Cancer Research Ireland (CRI)
Title : MicroRNA Regulation of the Spindle Assembly Checkpoint (SAC): Implications for Cell Cycle Dysregulation in Ovarian Cancer and Taxol Responsiveness
Start Date / End Date : 01-NOV-08 / 31-OCT-11
Sponsor : Irish Research Council for Science Engineering and Technology (IRCSET)
Title : Epigenetic downregulation of BRCA1 and MAD2:- a role in the underlying mechanisms of Taxol resistance in sporadic breast cancer
Start Date / End Date : 01-OCT-06 / 01-OCT-09
Sponsor : University College Dublin (UCD)
Title : Genomic and Expression Analysis of the c-MET/Hepatocyte Growth Factor (HGF) Complex in Human Bladder Cancer
Start Date / End Date : 01-JUL-02 / 30-JUN-03
Sponsor : Mater College for Postgraduate Education & Research
Title : Investigation of PRB, Gas6, Beta-catenin, and the EMT patheay as indicators of recurrence in breast cancer
Start Date / End Date : 01-JAN-05 / 31-DEC-05
Sponsor : Health Research Board (HRB)
Title : Automated Slide Scanning and Image Analysis System: Application to High Throughput Biomaker Validation Studies
Start Date / End Date : 01-JAN-05 / 30-JUN-05
Sponsor : Cancer Research Ireland (CRI)
Title : Epithelial Mesenchymal Transition (EMT) markers as predictors of recurrence in transitional cell carcinoma (TCC) of the bladder
Start Date / End Date : 01-NOV-04 / 31-OCT-07
Sponsor : Health Research Board (HRB)
Title : The significance of S100A4 and other novel candidate EMT markers as key modulators of the metastatic phenotype of TCCB
Start Date / End Date : 01-OCT-04 / 30-SEP-07
Sponsor : Mater Misericordiae University Hospital
Title : Characterisation of the Mitotic Assembly Deficient Proteins MAD and MAD2 in predicting breast tumour sensitivity to microtubule inhibitor (Taxol/Taxotere) Chemotherapy
Start Date / End Date : 01-JAN-04 / 31-DEC-04
Sponsor : Mater Misericordiae University Hospital
Title : Molecular profiling of PRA,PRB and ER alpha as an indicator for Endocrine therapy in breast cancer
Start Date / End Date : 01-JAN-04 / 31-DEC-04
Sponsor : Cancer Research Ireland (CRI)
Title : E-cadherin promoter methylation status and C-MET/HGF expression levels in transitional cell carcinoma of the bladder
Start Date / End Date : 01-NOV-03 / 30-OCT-06
Sponsor : Health Research Board (HRB)
Title : Light Cycler Real-Time PCR System
Start Date / End Date : 28-SEP-00 / 05-OCT-00
Sponsor : The Mater Foundation
Title : Imprinting and loss of heterozygosity (,OH) phenotypes of tumour suppressor gene TSSC5 (11 p15.5) in adult and childhood cancers
Start Date / End Date : 01-SEP-00 / 31-AUG-01
Sponsor : Danish Research Academy
Title : An investigation of chromosome 7 candidate imprinted genes in human breast cancer
Start Date / End Date : 01-APR-98 / 01-APR-01
Sponsor : Cancer Research Advancement Board
Title : Loss of heterozygosity (LOH) of the imprinted p57k1p2 and H19 tumour suppressor genes in human breast cancer
Start Date / End Date : 01-OCT-97 / 01-OCT-99
Sponsor : Health Research Board (HRB)
Title : De novo taxol resistance attributable to alterations in 2 key mitotic checkpoint proteins BRCA1 and MAD2
Start Date / End Date : 01-OCT-06 / 31-DEC-09
Sponsor : Mater College for Postgraduate Education & Research
Title : Alpha-T-catenin (CTNNA3) profiling in breast cancer and its relationship to tumour metastatis prognosis and the EMT process
Start Date / End Date : 01-JAN-06 / 31-DEC-06