Prof. Sharon Glynn is a 2022 Fulbright Scholar and Professorin Pathology at University of Galway. She was awarded a Science Foundation Ireland Career Development Award in 2018 for her research into the role of nitrosative stress and human endogenous retroviruses (HERV-K) in the development of high grade breast and prostate cancer. Her current work is focused on elucidating the role of inflammation pathways particularly in the progression of triple negative breast cancer and metastatic prostate cancer. She is the Coordinator of a MSCA Doctoral Network called NO-CANCER-NET.Prof. Glynn has authoredover 60 papers in peer reviewed journals and has also received numerousgrants fromBreast Cancer Now and the Irish Cancer Society. Shegraduated in 2003 with a BSc in Biotechnology from Dublin City University. After graduation she served as a research officer at the National Institute for Cellular Biotechnology in Dublin City University where she studied the efficacy of new therapeutics including cholesterol lowering statins on breast cancer and melanoma proliferation and invasion. From 2005 to 2009 Dr. Glynn worked as an NCI Cancer Prevention Fellow in Bethesda Maryland, USA in the Laboratory of Human Carcinogenesis under the mentorship of Dr. Stefan Ambs, studying the role of inflammation pathways in estrogen receptor negative breast cancer progression using an approach combining molecular epidemiology and basic laboratory science. She discovered a novel role for NOS2 in ER negative and basal-like breast cancer progression. Dr. Glynn also discovered a polymorphism in the SOD2 gene predicative of response to cyclophosphamide containing chemotherapeutic regimens in breast cancer cases, receiving an NIH Fellows Award for Research Excellence for this work. In September 2009 Dr. Glynn moved to the Radiation Biology Branch at the NCI, to continue working with Dr. David Wink. During this time she was awarded a Keystone Symposia Scholarship for her work.From September 2010 to December 2014 Dr. Glynn was the Director of Laboratory Researchat the Prostate Cancer Institute at NUI Galway (University of Galway).

Inflammation and Breast and Prostate CancerChronic 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. Genetic ablation of NOS2 increases mammary tumour latency and inhibits lung tumour development in mouse models of cancer. These genetic findings demonstrate that NOS2 can have tumour promoting activities. However, NOS2 expression or other forms of NO exposure are not always tumour promoting, and there are many examples where exposure to NO either delayed or inhibited tumour growth and metastasis. Because the effects of NO are strictly concentration-dependent with high concentrations causing cytostasis and apoptosis, at least some of the observed differences are likely explained by a difference in levels of NO exposure. The Prostate Cancer Bone Marrow Mesenchymal Stem Cells Para-endocrine Axis in the metastatic tumor microenvironmentMesenchymal stem cells (MSC) are multipotent stem cells that can differentiate into osteoblasts, chondrocytes, adipocytes, myocytes and neurons. They can be sourced from the bone marrow (BM) stroma, adipose tissue and dental pulp, and are also found in circulation and are known to home to inflammatory sites. Due to their capacity to home to injured tissue, research has suggested a reparative function for MSC in multiple tissues. In recent studies it has been shown that MSC can also home to tumour sites and contribute to tumour growth and progression. MSC have been shown to increase the metastatic potential of tumour cells by promoting their migration and invasion as well as having a role in the development of a metastatic niche at the secondary site. BM-MSC may also contribute to tumour growth by differentiating into cancer associated fibroblasts (CAFs), which form part of the tumour microenvironment. Additionally BM-MSCs are intrinsically radio- and chemo-resistant due to a heightened DNA damage response, and thus may contribute to treatment resistance. Our preliminary studies demonstrate that considerable baseline variations exist in the secretomes of primary BM-MSCs which impact the magnitude of their response to PrCa cell lines, and vice versa. This indicates that inter-patient BM-MSC variation, may impact on tumour microenvironment dynamics, influencing a patients risk of metastasis, and potentially therapeutic response. Our preliminary data has also identified members of the BM-MSC secretome that induce PrCa cell migration in a dose dependant manner, using recombinant growth factors at the concentrations produced by the BM-MSCs. Human Endogenous Retrovirus Activation in Breast and Prostate CancerIn recent years scientists have observed that several tumor types, including prostate cancer, show increased expression of human endogenous retrovirus (HERV) when compared to normal tissue. Why are these HERVs of interest? The HERVs originated from germ cell infections by exogenous retroviruses during the course of evolution and became incorporated into the human genome. These elements are widely dispersed throughout the genome and are estimated to comprise of greater than gt;8% of genomic material. Over 20 HERV families have been identified to date, the majority of which are defective due to mutations, deletions or termination signals within coding regions. 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. Several questions need to be asked about HERV-K in prostate cancer. Is HERV-K activation a bystander effect in prostate cancer or is it linked to active prostate progression; can it distinguish indolent from aggressive disease? What is the major activator of HERV-K expression in prostate cancer? Does chronic inflammation in prostate tissues lead to the activation of HERV-K expression or does activation of HERV-K lead to tissue inflammation and subsequent carcinogenesis? Pockets of inflammation are often observed in prostate tissues that are not actually cancerous tissue but are thought to be associated with increased risk of prostate cancer.If interested in pursuing applications for PhD funding, please contact me at [email protected]