Our laboratory research group has two broad areas of research activity.  Our group has an extensive cancer biobank of tissue, serum and plasma used to develop novel biomarkers for ovarian and other gynaecological cancers.  The group also investigates mechanisms of chemoresistance and recurrence in ovarian cancers. The second area of research activity involves the pathogenesis of thrombotic complications in obstetrics and gynaecology.   These include the development of risk models for prediction of venous thrombosis in gynaecological cancers, and determining the role of tumour expression of coagulation proteases in the aetiology of gynaecological cancers.  Our research is funded by Health Research Board, Emer Casey Foundation, St James Hospital Foundation Gynae Cancer appeal, Royal City of Dublin Hospital Trust Fund. 

Our group has an extensive biobank [DISCOVARY bioresource] of serum, blood and plasma and tissue from malignant and benign tumours. This biobank underpins all of our translational research and provides important material for investigating tumour markers which can help in early diagnosis and in more targeted treatments.  The bioresource is a collaborative effort between St James’s and Trinity College Dublin. This biobank is linked to a dedicated database which provides full clinical information and follow-up data on each patient.  This allows us to do studies looking at determinants of survival and treatment response.  To date it has recruited over 2000 patients and recruitment is ongoing.  A recent epidemiological review of 583 cases from our bioresource reveals our figures are in line with the national averages so we are confident our sample population is representative of the gynaecological cancer cases that present in Ireland. 

Our group participates in a nationwide network internationally recognised ovarian cancer clinical and scientific experts.  Established in 2014, the aim of INNOVATION is to integrate patient clinical pathways with cutting edge research to improve diagnosis and treatment of ovarian cancer.  Further information can be found here.  

All cancers are associated with an increased risk of clots to the legs and lungs however gynaecological cancers have a particularly high risk. A recent survey of patients who suffered a clot during their cancer journey showed that, generally, patients are not warned about the risk of clots during cancer and are not told what to look out for. Our group have produced a patient information leaflet explaining the risk of thrombosis in gynaecological cancer patients. The leaflet was launched at the OvaCare patient information day held in Cork. Ovacare is a patient support group for women with ovarian cancer (www.OvaCare.ie). The leaflet has been distributed to all centres treating gynaecological cancer patients in Ireland and is available in all Irish Cancer Society Daffodil Centres. This initiative was funded by the Health Research Board under its knowledge exchange program (KEDS). You can download the leaflet here (PDF 599 kB).

Gynaecological cancers have been associated with high rates of VTE which is exacerbated by pelvic surgery and chemotherapy. A recent study in our centre showed that one third of VTE in ovarian cancer patients occurs within 5 days of surgery despite heparin prophylaxis. Recently, clinical risk models have been developed to predict VTE in patients undergoing chemotherapy, these models have been shown to be more powerful when combined with haemostatic biomarkers. Global tests of hypercoagulability which capture these effects are therefore attractive as determinants of thrombotic risk. Calibrated automated thrombograpy (CAT) is a global test which measures thrombin generation in plasma. Increased thrombin generation is predictive of VTE in a variety of clinical settings. The overarching aim of this project is to develop and validate a specific risk scoring model for VTE risk in gynaecological cancer patients using a combination of easily available clinical and laboratory parameters and haemostatic biomarkers in n a large population of 1000 gynaecological cancer patients.

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We previously reported a venous thromboembolism (VTE) incidence of 9.7% in a large cohort of women with ovarian cancer from 2006 to 2010. Of these, 33% occurred in the first 28 days following surgery. In keeping with current international guidelines we introduced a policy of extended VTE prophylaxis with low molecular weight heparin (LMWH) for four post-operative weeks in January 2012.  The aim of this project is to determine the effect of the introduction of extended prophylaxis on the rate of post operative venous thrombosis in ovarian cancer since the introduction of these guidelines.

Ovarian cancers carry a high risk of thrombosis but coagulation activation and thrombin formation are also thought to play a role in tumorigenesis and metastasis. Preliminary data from our group has shown that the activated protein C pathway (aPC), is dysregulated in ovarian tumours. Type 1 ovarian cancers are predominantly chemoresistant and associated with a poor prognosis; a novel therapeutic approach is urgently required.  Reduced expression of key proteins in the aPC pathway (Thrombomodulin(TM), EPCR, protein S) combined with enhanced expression factor V were observed in tumour extracts; these changes were associated with reduced survival.  Using our biobank, we aim (1) to determine the role of EPCR, Factor V and TM as prognostic markers and to determine their role in survival.(2) using cell models, to determine the potential role of recombinant EPCR and TM as novel therapeutics in ovarian cancer.

Large scale studies have shown a strong link between a history of endometriosis and an increased risk of invasive clear cell and endometrioid cancers.  Our previous studies showed that Tissue Factor (TF), the major trigger for the coagulation cascade, is overexpressed in clear cell cancers but not in papillary serous or mucinous carcinoma. ).    Ectopic synthesis of factor VII is known to activate ovarian cancer cell migration and invasion.  Increased expression of both PAR-2 and TF in the eutopic and ectopic endometrium  from women with endometriosis compared with normal women has been reported however it is unknown whether a further increase in expression is implicated in malignant transformation of endometrioma into clear cell cancer.   Our hypothesis is that expression and activation of the TF-VIIa-PAR-2 signalling pathway is further increased in clear cell cancers particularly those formed on a background of endometriosis and that this may provide a potential target for treatment of clear cell cancers. The aim of the study is to compare the expression of TF, VIIa and PAR-2  in clear cell cancers with endometrial tissue from patients with endometriosis.

Patients with cancer have a higher risk of developing venous thromboembolism (VTE) and VTE is a major contributor to morbidity and mortality risk in these patients. Ovarian cancer, pancreatic cancer and glioblastoma are the cancers associated with the highest risk of VTE. The treatment and prevention of VTE is particularly challenging in gynaecological cancer. A recent study reported a VTE incidence of 11% of patients with ovarian cancer undergoing chemotherapy. The presence of a gynaecological malignancy increases the rate of post operative VTE fourfold compared with patients with benign disease. Genital tract cancers are a diverse group of diseases. The incidence of VTE in clear cell type of ovarian cancer has been found to be as high as 27%.  Cancer patients with VTE have a higher risk of recurrent VTE than those without malignancy. Nine percent of cancer patients who presented with VTE had a recurrence despite LMWH prophylaxis and 17% with a vitamin K antagonist in a mixed population of cancers (17).  The risk of recurrence is highest within the first 12 months and is most pronounced with concurrent cancer related events (e.g. disease progression or relapse).  Although gynaecological cancers are associated with one of the highest rates of cancer associated VTE, few studies have investigated VTE recurrence in gynaecological cancers.  This study aims to investigate the rate of recurrence of VTE in the gynaecological cancer population and the factors which influence VTE recurrence.