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Research

Dr Amanda McCann BA, PhD.

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 : 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