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

• Medicine
• General Practice
• Pathology
• Sports and Exercise Medicine

• Adolescent medicine
• Cardiology
• Dermatology
• Gastroenterology
• Neurology
• Oncology

I am a biologist focused on the study of signal transduction pathways and in particular how the deregulation of members of these pathways leads to the development of diseases and in particular cancer. My group accelerates the study of signal transduction processes by (i) developing new proteomics-based methods for the identification and mapping of new signalling networks; and (ii) applying systems biology approaches to develop kinetics models of signal transduction networks. We have a track record of success with this strategy having utilised it to map the tumour suppressor Hippo pathway in mammalian systems. Since delineating this pathway we have made key contributions in characterising its molecular regulatory mechanisms and in explaining the role of the pathway in normal a pathological cell signalling. We also study the family of Ras oncogenes which are mutated in over 30% of cancers. Using bespoke molecular and bioinformatics tools we have mapped the signalling networks mediated by different Ras mutants by performing proteomics screening. This information is being used to understand how mutant Ras tumours develop resistance to anti-Raf and MEK inhibitors and identify possible new druggable targets that can potentially lead to the discovery of new and improved treatments for patients.

Study of the role of the tumour suppressor RASSF1A in cancer.
RASSF1A is the most deregulated gene in human tumours and is commonly silenced by DNA methylation. This tumour suppressor is regulated by the oncogene KRAS and is an upstream regulator of the pro-apoptotic Hippo pathway that are the main subjects of research in the hosting group [1,2]. Despite the clear role of RASSF1A in cancer development we have very limited understanding of how the loss of expression of this protein causes cancer and how we can target this protein for anti-cancer treatments. Evidence suggests that re-expression of RASSF1A in tumours such as breast cancer, melanoma and colorectal cancer result in better response to anti-cancer therapy [3, 4] and in the case of breast cancer seems to be a potential biomarker for hormone therapy response. Thus, there is an urgent need to gain a better understanding of the role of this protein in cancer. The PhD student will use proteomics and molecular biology to map the RASSF1A signalling network in cancer cells and tumour samples. Using this information we will begin to understand the effect that loss of RASSF1A has in the cell and in particular how its lost desensitise the cell to common anticancer therapies. This work will be completed using clinical data and patient samples that can come from the student?s practice, therefore leveraging his/her field of expertise. This data will be integrated using systems biology approaches in collaboration with computational biologists in SBI. As a results of this multidisciplinary project the PhD student will become proficient in molecular biology and proteomics. He/she will be exposed to the multinational and multidisciplinary team in Systems Biology Ireland. More importantly the PhD will learn about systems biology/medicine approaches and how they can be translated into the clinic as part of the development of systems/personalised medicine and will be well-placed for a postdoctoral position if he/she wish to follow a career in biomedical research.
1. The MST/Hippo Pathway and Cell Death: A Non-Canonical Affair. Fallahi E, O'Driscoll NA, Matallanas D. Genes (Basel). 2016 Jun 17;7(6)
2. The complexities and versatility of the RAS-to-ERK signalling system in normal and cancer cells. Fey D, Matallanas D, Rauch J, Rukhlenko OS, Kholodenko BN. Semin Cell Dev Biol. 2016 Oct;58:96-107
3. Clinical utility of RASSF1A methylation in human malignancies. Grawenda AM, O'Neill E. Br J Cancer. 2015 Jul 28;113(3):372-81
4. Colorectal cancer and RASSF family--a special emphasis on RASSF1A. Fernandes MS, Carneiro F, Oliveira C, Seruca R.Int J Cancer. 2013 Jan 15;132(2):251-8.
5. RASSF1A Promoter Methylation Levels Positively Correlate with Estrogen Receptor Expression in Breast Cancer Patients. Kajabova V, Smolkova B, Zmetakova I, Sebova K, Krivulcik T, Bella V, Kajo K, Machalekova K, Fridrichova I. Transl Oncol. 2013 Jun 1;6(3):297-304.