Cancer is a disease of the genome. Genomic somatic mutations and alterations can change the function of genes, either promoting the expression of cancer causing genes or the loss of cancer suppressor genes. These genomic mutations/alterations drive cancer development, progression and ultimately drug resistance.
The major research interest of the translational cancer genomic research lab is to elucidate the tumour diversity caused by genomic alterations which contributes to cancer resistance to chemotherapy and molecular targeted therapies. We use genomic and functional genomic next generation sequencing (NGS) approaches to identify the mechanisms of genomic diversity to develop prognostic/predictive signatures and therapeutic strategies to overcome treatment resistance.
- Breast cancer: The CharactHER study (ICORG 10-09): Genomic and molecular characterisation of HER2-positive metastatic breast cancer patients treated with Trastuzumab (Herceptin®). Using IHC, FISH, flow cytometry, arrayCGH and next generation sequencing technologies, this study aims to identify the genomic profile signature of long-term durable complete responders (dCR) compared to non-responders.
- Solid tumours: The Outliers Study uses both positive (long-term dCRs of metastatic disease > 3 years) and negative (pCR < 6 mo) “outlier” patients to elucidate the genomic and molecular properties that predispose tumours to treatment sensitivity or resistance.
- Melanoma: 1. The MelGen Project uses NGS technology to investigate whether genomic profiling can predict response to immunotherapies. 2. Functional genomic applications to overcome Braf-inhibitor resistance in melanoma cancer cell models.
- Pancreatic cancer: The PanX study uses in vitro 3D spheroid models from established and primary cell lines and pancreatic cancer patient-derived xenografts (PDX) to define and validate the biological consequences of genomic variants from susceptibility loci regions identified through a NCI-collaborative PanScan GWAS pathway analysis multiplexed with the NGS profiles of pancreatic cancer.
Dr Naomi Walsh (email@example.com)
Mahgoub T, Eustace AJ, Collins DM, Walsh N, O'Donovan N, Crown J. (2015). Kinase inhibitor screening identifies CDK4 as a potential therapeutic target for melanoma. Int J Oncol 47:900-908
O'Sullivan D, Henry M, Joyce H, Walsh N, Auley EM, Dowling P, Swan N, Moriarty M, Barnham P, Clynes M, Larkin A. (2014). 7B7: a novel antibody directed against the Ku70/Ku80 heterodimer blocks invasion in pancreatic and lung cancer cells. Tumour Biol. 35(7):6983-97
Walsh N, Kennedy S, Larkin AM, Corkery B, O’Driscoll L, Clynes M, Crown J, O’Donovan N. (2013). EGFR and HER2 inhibition in pancreatic cancer. Investigational New Drugs. Jun 31(3):558-66
Walsh N, Larkin AM, Swan N, Conlon K, Dowling P, McDermott R, Clynes, M. (2011). RNAi knockdown of Hop (Hsp70/Hsp90 organising protein) decreases invasion via MMP-2 down regulation. Cancer Letters. Jul 306:2: 180-189
Walsh N, Kennedy S, Larkin AM, Tryfonopoulos D, Eustace AJ, Mahgoub T, Conway C, Oglesby I, Collins D, Ballot J, Ooi WS, Gullo G, Clynes M, Crown J, O’Driscoll L. (2010). Membrane transport proteins in human melanoma: associations with tumour aggressiveness and metastasis. British Journal of Cancer. Mar;102(7):1157-1162.
Walsh N, Clynes M, Crown J, O’Donovan N. (2009). Alterations in integrin expression modulates invasion of pancreatic cancer cells. Journal of Experimental & Clinical Cancer Research. Oct;28:140.
Walsh, N, O’Donovan N, Kennedy S, Henry M, Meleady P, Clynes M, Dowling P. (2009). Identification of pancreatic cancer invasion-related proteins by proteomic analysis. Proteome Science. Feb;7:3.
Walsh N, Dowling P, Henry M, Meleady P, O’Donovan N, Clynes M. (2008). Aldehyde dehydrogenase 1A1 and gelsolin identified as novel invasion-modulating factors in conditioned medium of pancreatic cancer cells. Journal of Proteomics. Dec;71(5):561-571.
*^O’Driscoll L, ^Walsh N, Larkin AM, Ballot J, Ooi WS, Gullo G, O’Connor R, Clynes M, Crown J, Kennedy S. (2007). MDR1/P-glycoprotein and MRP-1 Drug Efflux Pumps in Pancreatic Carcinoma. Anticancer Research. 27(4B):2115-2120. ^Joint authorship