Supervisor View Full Details 2nd

• genetics, genomics and molecular biology
• cancer/oncology
• epidemiology/population health research

• Medicine
• Surgery
• Pathology
• Public Health

• Immunology
• Oncology
• Pharmacology

The Glynn lab focuses on understanding inflammation related mechanisms and how they contribute to the initiation and progression of breast and prostate cancer contributing to poor patient outcomes. The lab has three main focuses of interest.
1. Nitrosative stress due to inducible nitric oxide synthase overexpression and its consequences for poor outcome in triple negative breast cancer.
2. The role of human endogenous retrovirus K in breast and prostate tumour progression.
3. Role of tumour infiltrating lymphocytes in triple negative breast cancer progression

Recent Publications Include:
Walsh EM, Shalaby A, O'Loughlin M, Keane N, Webber MJ, Kerin MJ, Keane MM, Glynn SA, Callagy GM. Outcome for triple negative breast cancer in a
retrospective cohort with an emphasis on response to platinum-based neoadjuvant therapy. Breast Cancer Res Treat. 2019 Feb;174(1):1-13.

O'Loughlin M, Andreu X, Bianchi S, Chemielik E, Cordoba A, Cserni G, Figueiredo P, Floris G, Foschini MP, Heikkilä P, Kulka J, Liepniece-Karele I,
Regitnig P, Reiner A, Ryska A, Sapino A, Shalaby A, Stovgaard ES, Quinn C, Walsh EM, Zolota V, Glynn SA, Callagy G. Reproducibility and predictive value of
scoring stromal tumour infiltrating lymphocytes in triple-negative breast cancer: a multi-institutional study. Breast Cancer Res Treat. 2018 Aug;171(1):1-9.

Ridge SM, Bhattacharyya D, Dervan E, Naicker SD, Burke AJ, Murphy JM, O'leary K, Greene J, Ryan AE, Sullivan FJ, Glynn SA. Secreted factors from metastatic
prostate cancer cells stimulate mesenchymal stem cell transition to a pro-tumourigenic 'activated' state that enhances prostate cancer cell migration. Int J Cancer. 2018 May 15;142(10):2056-2067.

Basudhar D*, Glynn SA*, Greer M, Somasundaram V, No JH, Scheiblin DA, Garrido P, Heinz WF, Ryan AE, Weiss JM, Cheng RYS, Ridnour LA, Lockett SJ, McVicar DW, Ambs S, Wink DA. Coexpression of NOS2 and COX2 accelerates tumor growth and reduces survival in estrogen receptor-negative breast cancer. Proc Natl Acad Sci U S A. 2017 Dec 5;114(49):13030-13035. *Joint first

Garrido P, Shalaby A, Walsh EM, Keane N, Webber M, Keane MM, Sullivan FJ, Kerin MJ, Callagy G, Ryan AE, Glynn SA. Impact of inducible nitric oxide synthase
(iNOS) expression on triple negative breast cancer outcome and activation of EGFR and ERK signaling pathways. Oncotarget. 2017 Jul 26;8(46):80568-80588.

Prueitt RL*, Wallace TA*, Glynn SA*, Yi M, Tang W, Luo J, Dorsey TH, Stagliano KE, Gillespie JW, Hudson RS, Terunuma A, Shoe JL, Haines DC, Yfantis HG, Han M,
Martin DN, Jordan SV, Borin JF, Naslund MJ, Alexander RB, Stephens RM, Loffredo CA, Lee DH, Putluri N, Sreekumar A, Hurwitz AA, Ambs S. An Immune-Inflammation Gene Expression Signature in Prostate Tumors of Smokers. Cancer Res. 2016 Mar 1;76(5):1055-1065. *Joint first

Wallace TA, Downey RF, Seufert CJ, Schetter A, Dorsey TH, Johnson CA, Goldman R, Loffredo CA, Yan P, Sullivan FJ, Giles FJ, Wang-Johanning F, Ambs S, Glynn SA.
Elevated HERV-K mRNA expression in PBMC is associated with a prostate cancer diagnosis particularly in older men and smokers. Carcinogenesis. 2014
Sep;35(9):2074-83.

Toner AP, McLaughlin F, Giles FJ, Sullivan FJ, O'Connell E, Carleton LA, Breen L, Dunne G, Gorman AM, Lewis JD, Glynn SA. The novel toluidine sulphonamide EL102 shows pre-clinical in vitro and in vivo activity against prostate cancer and circumvents MDR1 resistance. Br J Cancer. 2013 Oct 15;109(8):2131-41.

Potential projects include:
(1) Assessment of utility of human endogenous retrovirus-K as a diagnostic tool for prostate cancer and investigation of its role in cellular transformation and the development of metastatic prostate cancer.
(2) Assessment of the role of inflammation in the induction of human endogenous retrovirus-K in triple negative breast cancer and its impact on the tumour-immune interactions in the context of tumour progression and therapeutic response.
Previously, through to be part of the junk DNA, Human endogenous retrovirus (HERVs) have been found to be activated in numerous disease states. HERV-K is the most recent virus to be integrated into the human genome, and is activated in cancer including but not limited to melanoma, prostate cancer, breast cancer and pancreatic cancer. Studies suggest that HERV-K is associated with poor patient outcome and increased metastatic potential, however little is known about their mechanism of action. We have developed tools to manipulate HERV-K levels in cancer cells and are currently investigating the signalling pathways related to the Hallmarks of Cancer that are regulated by HERV-K. Of particular interest to us is the role of HERV-K in the modulation of the tumour microenvironment. These projects will involve investigation of HERV-K effects in vitro, followed by assessment of its role in our patient molecular cohort studies. In collaboration with the US National Cancer Institute and Houston Methodist Hospital we are developing new improved methods to examine 3D tumour milieu interactions in patient specimens, which we can then interrogate to assess their impact on tumour progression and treatment responses.