About
I possess over 20 years experience in the biopharmaceutical industry across the drug…
Articles by David
Activity
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Heading to the Bioprocessing Summit Europe 2025 in #Barcelona? Don't miss the chance to hear from 2 of our experts as they share insights on the…
Heading to the Bioprocessing Summit Europe 2025 in #Barcelona? Don't miss the chance to hear from 2 of our experts as they share insights on the…
Shared by David Murray
Experience
Education
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Dublin City University
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During my PhD studies I described and published on interactions between matrix metalloproteinase (MMPs) and CD44 in colorectal cancer (CRC) metastasis. The data obtained in this study supports the use of MMP bioactivity and CD44 expression as biomarkers and potential therapeutic targets thereby for the treatment of CRC patients. During the course of my doctoral training I spent 5 months at the Centre for Biomedical Genomics, George Mason University, VA, using microarray technology to identify…
During my PhD studies I described and published on interactions between matrix metalloproteinase (MMPs) and CD44 in colorectal cancer (CRC) metastasis. The data obtained in this study supports the use of MMP bioactivity and CD44 expression as biomarkers and potential therapeutic targets thereby for the treatment of CRC patients. During the course of my doctoral training I spent 5 months at the Centre for Biomedical Genomics, George Mason University, VA, using microarray technology to identify key genes and gene clusters that underpin metastasis. Various genes were chosen for further analysis. Through close interaction with gastroenterology specialists, expression of these genes in matched normal and tumour colon tissue was assessed, ensuring clinical relevance of analyses. This study significantly expanded the CRC knowledgebase. Data are likely to have a future impact on patient care as they further support the use of MMP and CD44 as biomarkers of disease or therapeutic targets.
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Subjects studied : Physical, organic, analytical and inorganic chemistry, microbiology, gene cloning & gene expression, advanced spectroscopy, cell culture & tissue biochemistry, mathamatics for scientists, physics for general science.
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Licenses & Certifications
Publications
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Prognostic significance of neuroepithelial transforming gene 1 in adenocarcinoma of the oesophagogastric junction.
Br J Surg. 2014 Jan;101(2):55-62
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Semapimod sensitizes glioblastoma tumors to ionizing radiation by targeting microglia
PLoS One
Glioblastoma is the most malignant and lethal form of astrocytoma, with patients having a median survival time of approximately 15 months with current therapeutic modalities. It is therefore important to identify novel therapeutics. There is mounting evidence that microglia (specialized brain-resident macrophages) play a significant role in the development and progression of glioblastoma tumors. In this paper we show that microglia, in addition to stimulating glioblastoma cell invasion, also…
Glioblastoma is the most malignant and lethal form of astrocytoma, with patients having a median survival time of approximately 15 months with current therapeutic modalities. It is therefore important to identify novel therapeutics. There is mounting evidence that microglia (specialized brain-resident macrophages) play a significant role in the development and progression of glioblastoma tumors. In this paper we show that microglia, in addition to stimulating glioblastoma cell invasion, also promote glioblastoma cell proliferation and resistance to ionizing radiation in vitro. We found that semapimod, a drug that selectively interferes with the function of macrophages and microglia, potently inhibits microglia-stimulated GL261 invasion, without affecting serum-stimulated glioblastoma cell invasion. Semapimod also inhibits microglia-stimulated resistance of glioblastoma cells to radiation, but has no significant effect on microglia-stimulated glioblastoma cell proliferation. We also found that intracranially administered semapimod strongly increases the survival of GL261 tumor-bearing animals in combination with radiation, but has no significant benefit in the absence of radiation. In conclusion, our observations indicate that semapimod sensitizes glioblastoma tumors to ionizing radiation by targeting microglia and/or infiltrating macrophages.
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Expression of neuroepithelial transforming gene 1 is enhanced in oesophageal cancer and mediates an invasive tumour cell phenotype.
J Exp Clin Cancer Res.
INTRODUCTION:
Neuroepithelial Transforming Gene 1 (NET1) is a well characterised oncoprotein and a proven marker of an aggressive phenotype in a number of cancers, including gastric adenocarcinoma. We aimed to investigate whether NET1 plays a functional role in oesophageal cancer (OAC) and its pre-malignant phenotype Barrett's oesophagus.
METHODS:
Baseline NET1 mRNA levels were determined by qPCR across a panel of six cell lines, including normal oesophageal, Barrett's and OAC derived…INTRODUCTION:
Neuroepithelial Transforming Gene 1 (NET1) is a well characterised oncoprotein and a proven marker of an aggressive phenotype in a number of cancers, including gastric adenocarcinoma. We aimed to investigate whether NET1 plays a functional role in oesophageal cancer (OAC) and its pre-malignant phenotype Barrett's oesophagus.
METHODS:
Baseline NET1 mRNA levels were determined by qPCR across a panel of six cell lines, including normal oesophageal, Barrett's and OAC derived cells. Quantification of NET1 protein in OAC cells was performed using Western blot and immunofluorescence. NET1 expression was modulated by treating with lysophosphatidic acid (LPA) and NET1-specific siRNA. The functional effects of NET1 knockdown were assessed in vitro using proliferation, migration and invasion assays.
RESULTS:
NET1 expression was increased in Barrett's and in OAC-derived cells in comparison to normal oesophageal cells. The highest expression was observed in OE33 a Barrett's-related OAC cell line. NET1 protein and mRNA expression was enhanced by LPA treatment in OAC and furthermore LPA treatment caused increased proliferation, migration and invasion in a NET1-dependent manner. NET1 knockdown resulted in reduced OAC cell proliferation and invasion.
CONCLUSIONS:
As found in other malignancies, NET1 expression is elevated in OAC and its pre-malignant phenotype, Barrett's oesophagus. NET1 promotes OAC cell invasion and proliferation and it mediates LPA-induced OAC cell migration.Other authors -
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HIV-1 protein induced modulation of primary human osteoblast differentiation and function via a Wnt/β-catenin-dependent mechanism.
J Orthop Res.
HIV infection is associated with metabolic bone disease resulting in bone demineralization and reduced bone mass. The molecular mechanisms driving this disease process have yet to be elucidated. Wnt/β-catenin signaling plays a key role in bone development and remodeling. We attempted to determine the effects of the HIV-1 protein, gp120, on Wnt/β-catenin signaling at an intracellular and transcriptional level in primary human osteoblasts (HOBs). This work, inclusive of experimental controls, was…
HIV infection is associated with metabolic bone disease resulting in bone demineralization and reduced bone mass. The molecular mechanisms driving this disease process have yet to be elucidated. Wnt/β-catenin signaling plays a key role in bone development and remodeling. We attempted to determine the effects of the HIV-1 protein, gp120, on Wnt/β-catenin signaling at an intracellular and transcriptional level in primary human osteoblasts (HOBs). This work, inclusive of experimental controls, was part of a greater project assessing the effects of a variety of different agents on Wnt/β-catenin signaling (BMC Musculoskelet Disord 2010;11:210).We examined the phenotypic effects of silencing and overexpressing the Wnt antagonist, Dickkopf-1 (Dkk1) in HOBs treated with gp120. HOBs exposed to gp120 displayed a significant reduction in alkaline phosphatase activity (ALP) activity and cell proliferation and increased cellular apoptosis over a 48 h time course. Immunocytochemistry demonstrated a significant reduction in intracytosolic and intranuclear β-catenin in response to HIV-1 protein exposure. These changes were associated with a reduction of TCF/LEF-mediated transcription, the transcriptional outcome of canonical Wnt β-catenin signaling. Silencing Dkk1 expression in HOBs exposed to gp120 resulted in increased ALP activity and cell proliferation, and decreased cellular apoptosis relative to scrambled control. Dkk1 overexpression exacerbated the inhibitory effect of gp120 on HOB function, with decreases in ALP activity and cell proliferation and increased cellular apoptosis relative to vector control. Wnt/β-catenin signaling plays a key regulatory role in HIV-associated bone loss, with Dkk1, aputative central mediator in this degenerative process.
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An Overview of microRNA Methods: Expression Profiling and Target Identification.
Methods Mol Biol. 2012;823:119-38.
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Direct effect of morphine on breast cancer cell function in vitro: role of the NET1 gene.
British Journal of Anaesthesia
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Cobalt ions induce chemokine secretion in a variety of systemic cell lines
Acta Orthop. 81(6):756-64
BACKGROUND AND PURPOSE: Metal ion toxicity both locally and systemically following MoM hip replacements remains a concern. Cobalt ions have been shown to induce secretion of proinflammatory chemokines locally; however, little is known about their effect systemically. We investigated the in vitro effect of cobalt ions on a variety of cell lines by measuring production of the proinflammatory chemokines IL-8 and MCP-1.
METHOD: Renal, gastrointestinal, and respiratory epithelium and also…BACKGROUND AND PURPOSE: Metal ion toxicity both locally and systemically following MoM hip replacements remains a concern. Cobalt ions have been shown to induce secretion of proinflammatory chemokines locally; however, little is known about their effect systemically. We investigated the in vitro effect of cobalt ions on a variety of cell lines by measuring production of the proinflammatory chemokines IL-8 and MCP-1.
METHOD: Renal, gastrointestinal, and respiratory epithelium and also neutrophils and monocytes were exposed to cobalt ions at 4, 12, 24, and 48 hours.
RESULTS: We found that cobalt ions enhanced the secretion of IL-8 and MCP-1 in renal epithelial cells, gastric and colon epithelium, monocytes and neutrophils, and small airway epithelial cells but not in alveolar cells. Secretion of IL-8 and MCP-1 was markedly elevated in renal epithelium, where a 16-fold and 7-fold increase occurred compared to controls. There was a 6-fold and 4-fold increase in IL-8 and MCP-1 secretion in colon epithelium and a 4-fold and 3-fold increase in gastric epithelium. Small airway epithelial cells showed a maximum increase in secretion of 8-fold (IL-8) and of 4-fold (MCP-1). The increase in chemokine secretion observed in alveolar cells was moderate and did not reach statistical significance. Monocytes and neutrophils showed a 2.5-fold and 2-fold increase in IL-8 secretion and a 6-fold and 4-fold increase in MCP-1 secretion at 48 and 24 hours, respectively.
INTERPRETATION: These data demonstrate the potent bioactivity of cobalt ions in a variety of cell types and the potential to induce a proinflammatory response.Other authors -
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Molecular Medicine Ireland Guidelines for Standardized Biobanking
Biopreservation and Biobanking. March 2010: 3-63.
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Effects of Sevoflurane on Breast Cancer Cell Function In Vitro.
Anticancer Res. 2013 Oct;33(10):4255-4260.
Some retrospective clinical studies have shown there to be an an association between the anaesthetic technique employed during breast cancer surgery and recurrence or metastases. Little is known about the direct effects of volatile anaesthetics on cancer cells. In the present study we investigated the effects of sevoflurane on estrogen receptor-positive (ER+) and estrogen receptor-negative (ER-) breast cancer cell functions that may contribute to metastatic potential.
MATERIALS AND…Some retrospective clinical studies have shown there to be an an association between the anaesthetic technique employed during breast cancer surgery and recurrence or metastases. Little is known about the direct effects of volatile anaesthetics on cancer cells. In the present study we investigated the effects of sevoflurane on estrogen receptor-positive (ER+) and estrogen receptor-negative (ER-) breast cancer cell functions that may contribute to metastatic potential.
MATERIALS AND METHODS:
MCF7 ER+ and MDA-MB-231 ER- breast cancer cells were incubated with or without sevoflurane, at concentrations of 1, 2, 3, and 4 mM for 6 h. Cell proliferation migration and invasion assays were then employed to measure for sevoflurane effects. An independent sample t-test analysis was used to compare for differences obtained between the groups.
RESULTS:
Sevoflurane increased proliferation in MCF7 cells by 50-63% and by 50-67% in MDA-MB-231 cells (p<0.05). Sevoflurane increased migration in both breast cancer cell lines, by 30-58% in MCF7 (p=0.04) and by 30-230% in MDA-MB-231; statistically significant at 2, 3 and 4 mM (p<0.03). Increase in invasion ranged from 100-170% in MCF7, (p=0.02) and 28-72% in the MDA-MB-231 cell line, statistically significant only at the 4-mM concentration.
CONCLUSION:
In this in vitro model of breast cancer cell function, sevoflurane increased proliferation, migration and invasion in ER-positive MCF7 cells and increased proliferation, and migration but not invasion in ER-negative cells. However, the observed effect size was small and not dose-dependent.Other authors -
Organizations
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Parenteral Drug Association
Member
- Presenthttps://www.pda.org/
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Regulatory Affairs Professionals Society
Member
- Presenthttps://www.raps.org/
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It was lovely to be nominated for the Women in Science Mentoring Awards with my UCD School of Biomolecular and Biomedical Science (SBBS) colleagues…
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I will be in Barcelona next week for the Bioprocessing Summit! Chairing the 'CMC for mRNA and RNA-based therapies' session and giving a talk on…
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Really inspired by the insightful discussions & highly innovative developments in immunotherapies presented at the AACR IO meeting in Los…
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Many thanks to Taylor & Francis Group for the opportunity to present this research article. My Parexel colleague Peter Kiely and I, undertook an…
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As Japan's role in global drug development grows, it's essential to understand its regulatory landscape and trial processes. Join my Parexel…
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A milestone has been reached: The Guideline for investigational ATMPs was published on the EMA Website! https://lnkd.in/dKX7ZBJt
A milestone has been reached: The Guideline for investigational ATMPs was published on the EMA Website! https://lnkd.in/dKX7ZBJt
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The public section of CTIS now enables a search for clinical trials taking place throughout Europe
The public section of CTIS now enables a search for clinical trials taking place throughout Europe
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Good news that the FDA thinking about the need for Phase III trials to support biosimilar filings is evolving. https://lnkd.in/eCQ5c5Vt
Good news that the FDA thinking about the need for Phase III trials to support biosimilar filings is evolving. https://lnkd.in/eCQ5c5Vt
Shared by David Murray
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Thank you New England Biolabs for organizing excellent wet lab training at EMBL in beautiful Heidelberg, Germany. Today we successfully made top…
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The EMA has published additional Q&As for biological products. Notably, the Q&A on Low Endotoxin Recovery (LER) has been updated to clarify the…
The EMA has published additional Q&As for biological products. Notably, the Q&A on Low Endotoxin Recovery (LER) has been updated to clarify the…
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S to P is a backward step according to the alphabet...but not in the case of SFHEA to PFHEA! Proud to share my recent Principal Fellow recognition by…
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The EMA has recommended granting a marketing authorization for Vyjuvek, the first gene therapy designed to treat wounds in patients with dystrophic…
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