Sharon Glynn 

Dr Sharon Glynn

 

Career History

Sept 2010-present: Director Laboratory Research, Prostate Cancer Institute, National Centre for Biomedical Engineering Science (NCBES), NUI Galway.
July 2009-Aug 2010: Visiting Fellow, Radiation Biology Branch, National Cancer Institute, Bethesda, Maryland, USA.
Sept 2005-June 2009: All-Ireland NCI Cancer Consortium Cancer Prevention Fellow, National Cancer Institute, Bethesda, Maryland, USA.
April 2003-Aug 2005: Postdoctoral Research Officer, National Institute for Cellular Biotechnology, Dublin City University

Research Interests

 

Inflammation and innate immune response pathways in prostate and breast cancer progression.


Nitric oxide signalling in cancer progression.


Human endogenous retrovirus K (HERV-K) activation in prostate cancer.
 

Research Overview

 

Chronic inflammation and infection are major mediators of cancer initiation and cancer progression. Key mediators of inflammation-induced cancer include NFkB, reactive oxygen and nitrogen species, inflammatory cytokines, prostaglandins and specific microRNAs, which in turn exert their effects though changes in cell proliferation, apoptosis, cellular senescence, DNA mutation rates, DNA methylation, cell invasiveness and angiogenesis. Together these species present the ideal targets for early detection, diagnosis, prediction of outcome and also therapeutic targets. Nitric oxide (NO) the product of nitric oxide synthase 2 (NOS2) can influence tumour biology in various and sometimes dichotomous ways. Research in the Glynn lab involves understanding the key mechanisms by which NO and prostaglandins interact to promote tumour progression.


A second strand of research revolves around the human endogenous retrovirus (HERV) K group. The HERVs originated from germ cell infections by exogenous retroviruses during the course of evolution and became incorporated into the human genome. The HERV-K family, evolutionarily the youngest HERV, is the only HERV family with complete open reading frames for all viral genes, and thus are the most likely to be biologically active and potentially pathogenic. We are examining the prevlanence of HERV-K activation in prostate cancer, and it impact on tumour progression. Is HERV-K activation a bystander effect in prostate cancer or is it linked to active prostate progression, distinguishing indolent from aggressive disease? Additionally we are exploring what are the major activators of HERV-K expression in prostate cancer.

 

Selection of key publications:

 

Ridnour LA, Cheng RY, Switzer CH, Heinecke JL, Ambs S, Glynn S, Young HA, Trinchieri G, Wink DA. Molecular Pathways: Toll-like Receptors in the Tumor Microenvironment: Poor Prognosis or New Therapeutic Opportunity. Clin Cancer Res. 2013 Mar 15;19(6): 1340-6.

Burke AJ, Giles FJ, Sullivan, FJ, Glynn SA. The Yin and Yang of nitric oxide in cancer progression. Carcinogenesis. 2013 Mar;34(3): 503-12.

Mee B, Gaffney E, Glynn SA, Donatello S, Carroll P, Connolly E, Garrigle SM, Boyle T, Flannery D, Sullivan FJ, McCormick P, Griffin G, Muldoon C, Fay J, O'Grady T, Kay E, Eustace J, Burke L, Sheikh AA, Finn S, Flavin R, Giles FJ. Development and Progress of Ireland's Biobank Network: Ethical, Legal, and Social Implications (ELSI), Standardized Documentation, Sample and Data Release, and International Perspective. Biopreservation and Biobanking 2013 Feb 1st;11 (1), 3-11.

Hudson RS, Yi M, Esposito D, Glynn SA, Starks AM, Yang Y, Schetter AJ, Watkins SK, Hurwitz AA, Dorsey TH, Stephens RM, Croce CM, Ambs S. MicroRNA-106b-25 cluster expression is associated with early disease recurrence and targets caspase-7 and focal adhesion in human prostate cancer. Oncogene. 2012 Sep 17. doi: 10.1038/onc.2012.424. IF = 6.3

Switzer CH, Cheng RY, Ridnour LA, Glynn SA, Ambs S, Wink DA. Ets-1 is a transcriptional mediator of oncogenic nitric oxide signaling in estrogen receptor-negative breast cancer. Breast Cancer Res. 2012 Sep 12;14(5):R125.

Ridnour LA, Barasch KM, Windhausen AN, Dorsey TH, Lizardo MM, Yfantis HG, Lee DH, Switzer CH, Cheng RY, Heinecke JL, Brueggemann E, Hines HB, Khanna C, Glynn SA, Ambs S, Wink DA. Nitric Oxide Synthase and Breast Cancer: Role of TIMP-1 in NO-mediated Akt Activation. PLoS One. 2012;7(9):e44081.

Switzer CH, Glynn SA, Cheng RY, Ridnour LA, Green JE, Ambs S, Wink DA. S-Nitrosylation of EGFR and Src Activates an Oncogenic Signaling Network in Human Basal-Like Breast Cancer. Mol Cancer Res. 2012 Sep;10(9):1203-15.

Zhao J, Rycaj K, Geng S, Li M, Plummer JB, Yin B, Liu H, Xu X, Zhang Y, Yan Y, Glynn SA, Dorsey TH, Ambs S, Johanning GL, Gu L, Wang-Johanning F. Expression of Human Endogenous Retrovirus Type K Envelope Protein is a Novel Candidate Prognostic Marker for Human Breast Cancer. Genes Cancer. 2011 Sep;2(9):914-22.

Switzer CH, Cheng RY, Ridnour LA, Murray MC, Tazzari V, Sparatore A, Del Soldato P, Hines HB, Glynn SA, Ambs S, Wink DA. Dithiolethiones inhibit NF-κB activity via covalent modification in human estrogen receptor-negative breast cancer. Cancer Res. 2012 May 1;72(9):2394-404.

Switzer CH, Ridnour LA, Cheng R, Heinecke J, Burke A, Glynn S, Ambs S, Wink DA. S-Nitrosation Mediates Multiple Pathways That Lead to Tumor Progression in Estrogen Receptor-Negative Breast Cancer. For Immunopathol Dis Therap. 2012;3(2):117-124.

Wang-Johanning F, Rycaj K, Plummer JB, Li M, Yin B, Frerich K, Garza JG, Shen J, Lin K, Yan P, Glynn SA, Dorsey TH, Hunt KK, Ambs S, Johanning GL. Immunotherapeutic potential of anti-human endogenous retrovirus-K envelope protein antibodies in targeting breast tumors. J Natl Cancer Inst. 2012 Feb 8;104(3):189-210.

Switzer CH, Glynn SA, Ridnour LA, Cheng RY, Vitek MP, Ambs S, Wink DA. Nitric oxide and protein phosphatase 2A provide novel therapeutic opportunities in ER-negative breast cancer. Trends Pharmacol Sci. 2011 Sep 3.

Ambs S, Glynn SA. Candidate pathways linking inducible nitric oxide synthase to a basal-like transcription pattern and tumor progression in human breast cancer. Cell Cycle, 2011 Feb 15;10(4):619-24.

Flores-Santana W, Salmon DJ, Donzelli S, Switzer CH, Basudhar D, Ridnour L, Cheng R, Glynn SA, Paolocci N, Fukuto JM, Miranda KM, Wink DA. The Specificity of Nitroxyl Chemistry Is Unique Among Nitrogen Oxides in Biological Systems. Antioxid Redox Signal. 2011 Mar 16.

Glynn SA, Prueitt RL, Ridnour LA, Boersma BJ, Dorsey TM, Wink DA, Goodman JE, Yfantis HG, Lee DH, Ambs S. COX-2 activation is associated with Akt phosphorylation and poor survival in ER-negative, HER2-positive breast cancer. BMC Cancer. 2010 Nov 15;10:626.

Glynn SA, Boersma BJ, Martin D, Howe TM, Ridnour LA, Wink DA, Yi M, Stephens RM, Yfantis HG and Ambs S. NOS2 predicts survival in estrogen receptor-negative breast cancer and is associated with a prognostic basal-like transcription pattern. J Clinical Investigation, 2010, 120, 3843-54.

Glynn SA, Boersma BJ, Howe TM, Edvardsen H, Geisler S, Goodman JE, Ridnour LA, Lonning PE, Børresen-Dale AL, Naume B, Kristensen VN, Chanock SJ, Wink DA, and Ambs S (2009) A mitochondrial targeting sequence polymorphism in the MnSOD gene predicts inferior survival in breast cancer patients treated with cyclophosphamide. Clinical Cancer Research, 2009, 15(12) 4165-73.

Glynn SA, O'Sullivan D, Eustace AJ, Clynes M, O'Donovan N. The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, simvastatin, lovastatin and mevastatin inhibit proliferation and invasion of melanoma cells. BMC Cancer. 2008 Jan 16;8(1):9

Dowling P, Maurya P, Meleady P, Glynn SA, Dowd AJ, Henry M, Clynes M. Purification and identification of a 7.6-kDa protein in media conditioned by superinvasive cancer cells. Anticancer Res. 2007 May-Jun;27(3A):1309-17.

Dowling P, Meleady P, Dowd A, Henry M, Glynn S, Clynes M. Proteomic analysis of isolated membrane fractions from superinvasive cancer cells. Biochim Biophys Acta. 2007 1774(1):93-101 IF = 3.6

Glynn SA, Adams A, Gibson B, Cronin D, Harmey JH, Clynes M. (2006) Low adhesiveness coupled with high superinvasiveness in vitro predicts the in vivo metastatic potential of a mouse mammary adenocarcinoma cell line. Anticancer Res, 26(2A), 1001-1010.

Glynn SA, Gammell P, Heenan M, O’Connor R, Liang Y, Keenan J and Clynes M. (2004) A new superinvasive in vitro phenotype induced by selection of human breast carcinoma cells with the chemotherapeutic drugs paclitaxel and doxorubicin. Br J Cancer, 91, 1800-1807.

O'Driscoll L, Cronin D, Kennedy SM, Purcell R, Linehan R, Glynn S, Larkin A, Scanlon K, McDermott EW, Hill AD, O'Higgins NJ, Parkinson M, Clynes M. (2004) Expression and prognostic relevance of Mcl-1 in breast cancer. Anticancer Res, 24, 473-482.

O'Driscoll L, Linehan R, Kennedy SM, Cronin D, Purcell R, Glynn S, McDermott EW, Hill AD, O'Higgins NJ, Parkinson M, Clynes M. (2003) Lack of prognostic significance of survivin, survivin-deltaEx3, survivin-2B, galectin-3, bag-1, bax-alpha and MRP-1 mRNAs in breast cancer. Cancer Lett, 201, 225-236.

Copyright ©2013 ARC - Apoptosis Research Group. All rights reserved.