Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn

PhD: Prof Brian Harvey - Endocrine modulation of colon cancer progression and tumorigenesis

The aim of this project is to determine the molecular mechanisms underlying sexual dimorphism in colorectal cancer tumorigenesis and patient survival.

A three-year funded PhD position is available in the Department of Molecular Medicine, RCSI, located in the Education and Research Building at Beaumont Hospital, Dublin.

The aim of this project is to determine the molecular mechanisms underlying sexual dimorphism in colorectal cancer tumorigenesis and patient survival.

Project title

Endocrine modulation of colorectal cancer progression and tumorigenesis

Project description

Colorectal cancer (CRC) is the third most common cancer in the world. Men are at higher risk than women of developing colorectal cancer with approximately 25% more men diagnosed than women. Pre-menopausal women have longer CRC patient survival than age-matched males. Despite the well documented gender discrepancy, a clear understanding of the mechanisms providing female protection from colorectal cancer is not yet available.

Recently published work from our research team has uncovered a new role for the potassium channel KCNQ1 as a tumour suppressor in colorectal cancer (Rapetti-Mauss et al., PNAS 2017, PMID: 28373572). KCNQ1 is a known target gene of Wnt/B-catenin. We have demonstrated that KCNQ1 can also bind to B-catenin, stabilising it at adherens junctions and maintaining a well differentiated epithelial phenotype. The B-catenin:T-cell factor 4 transcriptional pathway directly represses KCNQ1 expression and the loss of KCNQ1 was associated with an epithelial to mesenchymal transition.

The purpose of this PhD project is to uncover molecular mechanisms underlying sexual dimorphism in colorectal cancer. The project will build on existing data to examine estrogen regulation of known tumour regulatory pathways including KCNQ1, Wnt signalling and other potassium channels of interest (KCNN4, KCNE3).

The project will use a variety of molecular biology skills and techniques including cell culture, electrophysiology, confocal microscopy, Western blotting, polymerase chain reaction, cell growth assays, proximity ligation assays, bioinformatics,. It is anticipated that results from this project will provide important information on mechanisms of cancer progression with the potential to impact cancer diagnosis and treatment.

  • Research theme: Colorectal cancer
  • Keyword: Colorectal cancer molecular mechanisms, estrogen, ion channels.

Required qualifications

Applicants should have an upper class Honours Degree in a relevant biological science subject.

Application process

Candidates should email a copy of their CV and a letter of motivation to Prof. Brian Harvey and Dr Jean McBryan.

Please include contact details of three referees. Closing date for applications is 5pm on Friday, 25 August 2017. Interviews for shortlisted candidates will take place in September 2017.

Mentors Prof. Brian Harvey, Dr Jean McBryan, Dr Warren Thomas