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• genetics, genomics and molecular biology
• physiology and non-communicable disease
• cancer/oncology
• Other - please suggest keyword(s):

• Medicine

• Endocrinology
• Oncology
• Physiology
• Respiratory Medicine

The RCSI Department of Molecular Medicine (www.rcsi.ie/molmed) is based at Beaumont Hospital, Dublin. The modern laboratories are equipped with state-of-the-art facilities for molecular biology, genetic manipulation, bioinformatics and proteomics, molecular and cellular imaging, electrophysiology and cell culture. Translational Research in the Department involves clinicians and scientists in areas of oncology, endocrinology, respiratory medicine, renal physiology and inflammatory disease. The major research focus is in endocrine modulated disease such as estrogen-dependent cancers (breast, ovarian, colon, lung), estrogen modulated respiratory disease (Cystic Fibrosis Gender Gap), aldosterone modulated renal function (hypertension) and their genetic and molecular basis with the aim to identify novel diagnostic and therapeutic targets. The hospital location makes the department ideal for training clinician PhDs.
Recent Publications:
Reihill JA et al. Inhibition of Protease-ENaC Signaling Improves Mucociliary Function in Cystic Fibrosis Airways. Am J Respir Crit Care Med. 2016 Mar 25.
McBryan J. et al. Transcriptomic Profiling of Sequential Tumors from Breast Cancer Patients Provides a Global View of Metastatic Expression Changes Following Endocrine Therapy. Clin Cancer Res. 2015 Dec 1;21(23):5371-9.
Elster N et al. HER2-family signalling mechanisms, clinical implications and targeting in breast cancer. Breast Cancer Res Treat. 2015 Jan;149(1):5-15.
Jennings CJ et al. Differential p16/INK4A cyclin-dependent kinase inhibitor expression correlates with chemotherapy efficacy in a cohort of 88 malignant pleural mesothelioma patients. Br J Cancer. 2015 Jun 30;113(1):69-75.
Saint-Criq V, Harvey BJ. Estrogen and the cystic fibrosis gender gap. Steroids. 2014 Mar;81:4-8.
Al-Alawi M et al. Physiological levels of lipoxin A4 inhibit ENaC and restore airway surface liquid height in cystic fibrosis bronchial epithelium. Physiol Rep. 2014 Aug 7;2(8). pii: e12093.
Dooley R et al. Aldosterone-induced ENaC and basal Na+/K+-ATPase trafficking via protein kinase D1-phosphatidylinositol 4-kinaseIII? trans Golgi signalling in M1 cortical collecting duct cells. Mol
Cell Endocrinol. 2013 Jun 15;372(1-2):86-95.
Stordal B. et al. (2013). BRCA1/2 mutation analysis in 41 ovarian cell lines reveals only one functionally deleterious BRCA1 mutation Molecular Oncology, 7(3), 567?579.
O'Mahony F et al. . Estrogen Modulates Metabolic Pathway Adaptation to Available Glucose in Breast Cancer Cells. Mol Endo. 2012 December, Vol 26 (12).
Jennings CJ et al. Sustained expression of steroid receptor coactivator SRC-2/TIF-2 is associated with better prognosis in malignant pleural mesothelioma. J Thorac Oncol. 2012 Jan;7(1):243-8.
Chotirmall SH et al. Effect of estrogen on pseudomonas mucoidy and exacerbations in cystic fibrosis. N Engl J Med. 2012 May 24;366(21):1978-86.

MIGRATORY CELLS IN BREAST CANCER: This project builds on a recently established technique to culture breast tumour tissue ex vivo. By incorporating biomaterials into the tumour culture , we can alter the frequency with which cells migrate away from the tumour mass. The project will characterise the migrating cells and compare to those still associated with the tumour mass using immunohistochemistry, PCR and next generation sequencing.

A NOVEL ROLE FOR DRUGS THAT INHIBIT IAP PROTEINS IN THE TREATMENT OF INCURABLE OVARIAN CANCER: PARP (poly-ADP ribose polymerase) inhibitors are a new class of drugs used to treat women with ovarian cancer, but these drugs are only effective in a minority (<20%) of cases (BRCA1/2-mutated cases). IAP (anti-apoptosis protein) inhibitors are a new class of drugs which increase the anti-cancer activity of PARP inhibitors. This project will investigate the potential of IAP inhibitors to be translated into a clinical trial to improve the treatment of women with advanced ovarian cancer.

ESTROGEN-MODULATED TUMORIGENESIS IN COLORECTAL CANCER (CRC): This project builds on our recent discovery of a novel estrogen-modulated Wnt/B-catenin:ion channel pathway regulating epithelial mesenchymal transition in CRC cells. The project will investigate estrogen protection in CRC through the modulation of the novel Wnt/B-catenin:ion channel signalling pathway and its target genes regulating cell differentiation, proliferation, invasion and migration. PhD training will involve bioinformatics, molecular endocrinology, gene manipulation and confocal microscopy.

THE ROLE OF ESTROGEN IN MICROBIAL VIRULENCE IN CYSTIC FIBROSIS LUNG: Females with CF have lower life expectancy compared to males (CF Gender Gap). This project is based on our discovery of the exacerbating effects of estrogen on mucociliary clearance, ion transport and microbial virulence in female CF airways. The project will focus on the molecular mechanisms for the sexual dimorphism of estrogen effects in CF airway surface liquid dynamics and Pseudomonas aeruginosa virulence.