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Amanda McCann

Senior Lecturer

School Of Medicine & Medical Science
Conway Institute
Belfield
Dublin 4

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

Biography

2004, 2002, 1997, 1993 Awarded a President's Research Award from UCD
1997-Present 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

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]
Jin Y, Amaral A, McCann A, Brennan L; (2011) 'Homocysteine levels impact directly on epigenetic reprogramming in astrocytes'. Neurochemistry International, . [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]
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]
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]
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]
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]
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]
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, McGrogan BT, Gilmartin B, Carney DN, ; (2008) 'Taxanes, microtubules and chemoresistant breast cancer'. 1785 (2):96-132. [DOI] [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). [DOI] [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]
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'. Cancer, 98 (6):1141-1146. [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'. J IMMUNOL, 180 :7125-7133. [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]
Nolan CM, O'Sullivan FM, Murphy SK, Simel LR, McCann A, Callanan JJ, ; (2007) 'Imprinted expression of the canine IGF2R, in the absence of an anti-sense transcript or promoter methylation'. Evolution and Development, 6 (NA):579-589. [DOI] [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]
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]
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]
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]
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]
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'. Rea, 92 :287-293. [DOI] [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'. Ejso, 30 (5):469-474. [Details]
Balfe, PJ; McCann, AH; Welch, HM; Kerin, MJ; ; (2004) 'Estrogen receptor beta and breast cancer'. Ejso, 30 (10):1043-1050. [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]
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]
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, 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]
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]
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]
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]
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]
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; 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'. Cancer, 88 :871-878. [DOI] [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; 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]
Pedersen, I.S., Dervan, P.A., McGoldrick, A., Harrison, M., Ponchel, F., Speirs, V., Isaacs, J.D., Gorey, T., and McCann, A.; (2002) 'Promoter switch: a novel mechanism causing biallelic PEG1/MEST expression in invasive breast cancer'. Human Molecular Genetics, 11 (12). [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]
McGoldrick, A; McCann, A; Fitzpatrick, J; Smith, J; Dervan, PA; ; (2002) 'Has bladder cancer MET its maker?'. Journal of 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'. Gene, 11 :1449-1453. [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]
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]
McGoldrick, A; McCann, A; Fitzpatrick, J; Smith, J; Dervan, PA; ; (2002) 'Has bladder cancer MET its maker?'. Journal of Pathology, 198 (NA):41-41. [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) 'Microarray generated oncogene copy number profiling in human bladder cancer'. British Journal of Cancer, 86 (NA):23-23. [Details]
McGoldrick, A; McCann, A; Fitzpatrick, J; Smith, J; Dervan, PA; ; (2002) 'Has bladder cancer MET its maker?'. Journal of Pathology, 198 (NA):41-41. [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]
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]
Pedersen, IS,Dervan, PA,Broderick, D,Harrison, M,Miller, N,Delany, E,O'Shea, D,Costello, P,McGoldrick, A,Keating, G,Tobin, B,Gorey, T,McCann, A; (1999) 'Frequent loss of imprinting of PEG1/MEST in invasive breast cancer'. Cancer, 59 (NA):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]
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 (6):661-665. [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]
Costello, P; McCann, AH; Moore, E; Gorey, T; Dervan, PA; ; (1998) 'Clonal analysis of breast DCIS using differential methylation of HUMARA'. British Journal of Cancer, 78 (NA):11-11. [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]
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]
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]
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)'. MODERN PATHOLOGY, 11 (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]
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, 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]
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

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]
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 * Dublin, Ireland, [Details]
                       

Abstract

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]
                                                               

Research

Research Interests

  • 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 : 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
 

Current Postgraduate Students

Elma O Reilly, Medicine (MD)   -   Thesis Supervisor
Luke Gubbins, Master of Science (MSc)   -   Thesis Supervisor
Karolina Weiner-Gorzel, Doctor of Philosophy (PhD)   -   Thesis Supervisor

Teaching

 

Modules Coordinated

201200   PATH30090     Pathology: SMMS Research Elective II
201200   MDSA30180     Medicine Systems One: SMMS Research Elective
201200   PATH30190     Pathology: Oncology & Immunopathology