Researcher Details |

Keith Rochfort

Dr.

Contact Details

H231
T:Ext. 6919

E:Keith.Rochfort@dcu.ie

Asst. Professor in Biosciences
School of Nursing, Psychotherapy, and Community Health
Dublin City University
Glasnevin
Dublin 9
T:+1 700 6919

E:Keith.Rochfort@dcu.ie

Dr. Keith Rochfort is an Assistant Professor of Biosciences based in the School of Nursing, Psychotherapy and Community Health/National Institute for Cellular Biotechnology (NICB). He received his BSc. in Analytical Science (2004) and PhD in Vascular Science (2013) from Dublin City University. Part of PRTLI Targeted Therapeutics and Theranostics (T3) Program, his PhD focused on endothelial cell signalling and blood vessel remodeling in response to health and disease. Upon graduating, he undertook a Science Foundation Ireland-funded Postdoctoral position with the Conway Institute at University College Dublin (2013-2016), before returning to DCU as a Senior Research Scientist as part of a Science Foundation Ireland US-Ireland Research Program developing genomic therapeutics towards vascular disease (2016-2018). He was hired as Assistant Professor by the School of Biotechnology in 2018, before moving to the School of Nursing, Psychotherapy, and Community Health (2021-Present), delivering and coordinating modules for Schools within the Faculty of Science and Health, and Faculty of Engineering and Computing, whilst also advancing his research as part of the Endothelial Biology Group at DCU. His research interests include healthy ageing and sustainability, with an focus on environmental factors which drive the pathological mechanisms and associated signalling events of vascular disease states, and developing diagnostic and therapeutic interventions towards such.

Peer Reviewed Journal

	Year	Publication
	2023	Kostyunina, DS;Rowan, SC;Pakhomov, NV;Dillon, E;Rochfort, KD;Cummins, PM;O'Rourke, MJ;McLoughlin, P (2023) 'Shear Stress Markedly Alters the Proteomic Response to Hypoxia in Human Pulmonary Endothelial Cells'. American Journal of Respiratory Cell and Molecular Biology, . [DOI]
	2023	Geoghegan, N;O'Loughlin, M;Delaney, C;Rochfort, KD;Kennedy, M;Kolagatla, S;Podhorska, L;Rodriguez, BJ;Florea, L;Kelleher, SM (2023) 'Controlled degradation of polycaprolactone-based micropillar arrays'. Biomaterials Science, . [DOI]
	2021	Leahy, R;Rochfort, KD;Whyte, E;Kontos, AP;Collins, MW;O'Connor, S (2021) 'Concussion in Ladies Gaelic Football: Self-reported History, Clinical Profiles, and Management Behavior'. Clinical journal of sport medicine : official journal of the Canadian Academy of Sport Medicine, . [DOI]
	2021	Wallace, RG;Rochfort, KD;Barabas, P;Curtis, TM;Uehara, H;Ambati, BK;Cummins, PM (2021) 'COMP-Ang1: Therapeutic potential of an engineered Angiopoietin-1 variant'. Vascular Pharmacology, . [DOI]
	2020	Harper E, Rochfort KD, Smith D, Cummins PM (2020) 'RANKL treatment of vascular endothelial cells leading to paracrine pro-calcific signaling involves ROS production'. Molecular and Cellular Biochemistry, 464 :111-117. [Link]
	2020	Forde, H;Harper, E;Rochfort, KD;Wallace, RG;Davenport, C;Smith, D;Cummins, PM (2020) 'TRAIL inhibits oxidative stress in human aortic endothelial cells exposed to pro-inflammatory stimuli'. Physiological Reports, 8 . [DOI]
	2019	Harper, E;Rochfort, KD;Smith, D;Cummins, PM (2019) 'RANKL treatment of vascular endothelial cells leading to paracrine pro-calcific signaling involves ROS production'. Molecular and Cellular Biochemistry, . [DOI]
	2019	Harper E, Rochfort KD, Smith D, Cummins PM (2019) 'RANKL treatment of vascular endothelial cells leading to paracrine pro-calcific signaling involves ROS production'. Molecular and Cellular Biochemistry, . [Link] [DOI]
	2019	Rochfort KD, Carroll LS, Barabas P, Curtis TM, Ambati BK, Barron N, Cummins PM (2019) 'COMP-Ang1 Stabilizes Hyperglycemic Disruption of Blood-Retinal Barrier Phenotype in Human Retinal Microvascular Endothelial Cells'. Investigative Ophtalmology and Visual Science, 60 :3547-3555. [Link]
	2019	Rochfort, K.D.;Carroll, L.S.;Barabas, P.;Curtis, T.M.;Ambati, B.K.;Barron, N.;Cummins, P.M. (2019) 'COMP-ang1 stabilizes hyperglycemic disruption of blood-retinal barrier phenotype in human retinal microvascular endothelial cells'. Investigative Ophthalmology and Visual Science, 60 . [Link] [DOI]
	2018	Harper E, Rochfort KD, Forde H, Davenport C, Smith D, Cummins PM (2018) 'Activation of the non-canonical NF-kB/p52 pathway in vascular endothelial cells by RANKL elicits pro-calcific signalling in co-cultured smooth muscle cells'. Cellular Signalling, 47 :142-150. [Link]
	2018	Harper, E;Rochfort, KD;Forde, H;Davenport, C;Smith, D;Cummins, PM (2018) 'Activation of the non-canonical NF-kappa B/p52 pathway in vascular endothelial cells by RANKL elicits pro-calcific signalling in co-cultured smooth muscle cells'. Cellular Signalling, 47 :142-150. [DOI]
	2018	Rowan SC, Rochfort KD, Piouceau L, Cummins PM, O'Rourke M, McLoughlin P (2018) 'Pulmonary endothelial permeability and tissue fluid balance depend on the viscosity of the perfusion solution'. American Journal of Physiology - Lung Cellular and Molecular Physiology, 315 :L476-L484. [Link]
	2018	Rowan, SC;Rochfort, KD;Piouceau, L;Cummins, PM;O'Rourke, M;McLoughlin, P (2018) 'Pulmonary endothelial permeability and tissue fluid balance depend on the viscosity of the perfusion solution'. American Journal of Physiology - Lung Cellular and Molecular Physiology, 315 :476-484. [DOI]
	2018	Davenport C, Harper E, Rochfort KD, Forde H, Smith D, Cummins PM. (2018) 'RANKL inhibits the production of OPG from smooth muscle cells under basal conditions and following exposure to cyclic strain'. Journal of Vascular Research, 55 :111-123. [DOI]
	2017	Harper E, Rochfort KD, Forde H, Davenport C, Smith D, Cummins PM. (2017) 'TRAIL attenuates RANKL-mediated osteoblastic signalling in vascular cell mono-culture and co-culture models'. PLoS ONE, 12 . [Link]
	2017	Harper, E;Rochfort, KD;Forde, H;Davenport, C;Smith, D;Cummins, PM (2017) 'TRAIL attenuates RANKL-mediated osteoblastic signalling in vascular cell mono-culture and co-culture models'. PLoS ONE, 12 . [DOI]
	2017	Degryse, B;Britto, M;Shan, CX;Wallace, RG;Rochfort, KD;Cummins, PM;Meade, G;Murphy, RP (2017) 'Moesin and merlin regulate urokinase receptor-dependent endothelial cell migration, adhesion and angiogenesis'. International Journal of Biochemistry and Cell Biology, 88 :14-22. [DOI]
	2017	McLoughlin, A;Rochfort, KD;McDonnell, CJ;Kerrigan, SW;Cummins, PM (2017) 'Staphylococcus aureus-mediated blood-brain barrier injury: an in vitro human brain microvascular endothelial cell model'. Cellular Microbiology, 19 . [DOI]
	2017	Degryse B.;Britto M.;Shan C.;Wallace R.;Rochfort K.;Cummins P.;Meade G.;Murphy R. (2017) 'Data on the regulation of moesin and merlin by the urokinase receptor (uPAR): Model explaining distal activation of integrins by uPAR'. Data In Brief, 15 :600-605. [DOI]
	2016	Forde H, Harper E, Davenport C, Rochfort KD, Murphy RP, Smith D, Cummins PM (2016) 'The beneficial pleiotropic effects of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) within the vasculature: A review of the evidence'. Atherosclerosis, 247 :87-96. [Link]
	2016	Rochfort, KD;Collins, LE;McLoughlin, A;Cummins, PM (2016) 'Tumour necrosis factor-alpha-mediated disruption of cerebrovascular endothelial barrier integrity in vitro involves the production of proinflammatory interleukin-6'. Journal of Neurochemistry, 136 :564-572. [DOI]
	2016	Rochfort KD, Collins L, McLoughlin A, Cummins PM. (2016) 'Tumour necrosis factor-α-mediated disruption of cerebrovascular endothelial barrier integrity in vitro involves the production of proinflammatory interleukin-6'. Journal of Neurochemistry, 136 (3):564-572. [Link] [DOI]
	2016	Davenport C.;Harper E.;Forde H.;Rochfort K.;Murphy R.;Smith D.;Cummins P. (2016) 'RANKL promotes osteoblastic activity in vascular smooth muscle cells by upregulating endothelial BMP-2 release'. International Journal of Biochemistry and Cell Biology, 77 :171-180. [DOI]
	2015	Rochfort KD, Collins LE, McLoughlin A, Cummins PM. (2015) 'Shear-dependent attenuation of cellular ROS levels can suppress proinflammatory cytokine injury to human brain microvascular endothelial barrier properties'. Journal of Cerebral Blood Flow and Metabolism, 35 (10):1648-1656. [Link] [DOI]
	2015	Collins LE;DeCourcey J;Soledad di Luca M;Rochfort KD;Loscher CE; (2015) 'An Emerging Role for SNARE Proteins in Dendritic Cell Function'. Frontiers in Immunology, 6 . [DOI]
	2015	Rochfort KD, Cummins PM. (2015) 'Cytokine-mediated dysregulation of zonula occludens-1 properties in human brain microvascular endothelium'. Microvascular Research, 100 :48-53. [Link] [DOI]
	2015	Rochfort KD, Cummins PM. (2015) 'Thrombomodulin regulation in human brain microvascular endothelial cells in vitro: Role of cytokines and shear stress'. Microvascular Research, 97 :1-5. [Link] [DOI]
	2015	Rochfort K.;Cummins P. (2015) 'The blood-brain barrier endothelium: A target for pro-inflammatory cytokines'. Biochemical Society Transactions, 43 :702-706. [DOI]
	2014	Rochfort K.;Collins L.;Murphy R.;Cummins P. (2014) 'Downregulation of blood-brain barrier phenotype by proinflammatory cytokines involves NADPH oxidase-dependent ROS generation: Consequences for interendothelial adherens and tight junctions'. PLoS ONE, 9 (7). [DOI]
	2014	Martin F.;McLoughlin A.;Rochfort K.;Davenport C.;Murphy R.;Cummins P. (2014) 'Regulation of thrombomodulin expression and release in man aortic endothelial cells by cyclic strain'. PLoS ONE, 9 (9). [DOI]
	2013	Guinan, AF;Rochfort, KD;Fitzpatrick, PA;Walsh, TG;Pierotti, AR;Phelan, S;Murphy, RP;Cummins, PM (2013) 'Shear stress is a positive regulator of thimet oligopeptidase (EC3.4.24.15) in vascular endothelial cells: consequences for MHC1 levels'. Cardiovascular Research, 99 :545-554. [DOI]
	2011	Walsh T.;Murphy R.;Fitzpatrick P.;Rochfort K.;Guinan A.;Murphy A.;Cummins P. (2011) 'Stabilization of brain microvascular endothelial barrier function by shear stress involves VE-cadherin signaling leading to modulation of pTyr-occludin levels'. Journal of Cellular Physiology, 226 (11):3053-3063. [DOI]

Book Chapter

	Year	Publication
	2019	Rochfort KD, Cummins PM (2019) 'In vitro cell models of the human blood-brain barrier: demonstrating the beneficial influence of shear stress on brain microvascular endothelial cell phenotype' In: Blood-Brain Barrier, NeuroMethods. New York, NY : Humana Press. [Link]
	2017	Cummins PM, Rochfort KD, O'Connor BF. (2017) 'Ion-Exchange Chromatography: Basic Principles and Application' In: Methods in Molecular Biology Vol.1485. United States : Humana Press. [Link]
	2017	Cummins, PM;Rochfort, KD;O'Connor, BF (2017) 'Ion-Exchange Chromatography: Basic Principles and Application' In: PROTEIN CHROMATOGRAPHY: METHODS AND PROTOCOLS, 2ND EDITION. TOTOWA : HUMANA PRESS INC. [DOI]
	2016	Philip M. Cummins, K.D. Rochfort and Brendan O’Connor (2016) 'Ion Exchange Chromatography Principles and applications' In: Methods in Molecular Biology. New York, USA : Springer. [DOI]

Conference Contribution

	Year	Publication
	2021	Kostyunina D, Dillon E, Rochfort KD, Cummins PM, McLoughlin P (2021) New Trends in Sex and Gender Medicine Sex different responses to hypoxia in male and female human pulmonary microvascular endothelial cells according to proteomics analysis American Physiological Society Virtual, .
	2019	Rochfort KD, Carroll LS, Barabas P, Curtis TM, Ambati BK, Barron N, Cummins PM. (2019) 43rd Annual Meeting of the Irish Endocrine Society Hyperglycemic disruption of blood-retinal barrier phenotype in human retinal microvascular endothelial cells is mitigated with COMP-Ang1 treatment. [WINNER: O’Donovan Medal - Best Speaker Category] Galway, Ireland, .
	2018	Rochfort KD, Barabas P, Carroll LS, Curtis TM, Ambati BK, Barron N, Cummins PM (2018) 42nd Meeting of the Irish Endocrine Society COMP-Ang1 stabilizes hyperglycemic disruption of blood-retinal barrier phenotype in human retinal microvascular endothelial cells Cork, Ireland, .
	2018	Rochfort KD, Barabas P, Carroll LS, Curtis TM, Ambati BK, Barron N, Cummins PM (2018) New Frontiers in Ocular Therapeutics COMP-Ang1 stabilizes hyperglycemic disruption of blood-retinal barrier phenotype in human retinal microvascular endothelial cells University College Dublin, Ireland, .
	2018	Harper E, Rochfort KD, Smith D, Cummins PM (2018) 42nd Annual Meeting of the Irish Endocrine Society TRAIL protects from RANKL-induced calcification in the aortic endothelium via an anti-oxidant mechanism Cork, Ireland, .
	2018	Rochfort KD, Barabas P, Carroll LS, Curtis TM, Ambati BK, Barron N, Cummins PM (2018) 50th Meeting of the International Society for Eye Research COMP-Ang1 stabilizes hyperglycemic disruption of blood-retinal barrier phenotype in human retinal microvascular endothelial cells Belfast, Northern Ireland, .
	2017	Harper E, Forde H, Davenport C, Rochfort KD, Smith D, Cummins PM. (2017) 41st Annual Meeting of the Irish Endocrine Society TRAIL protects from RANKL-induced calcification in an in vitro vascular co-culture model, in part via attenuation of NF-κB pro-calcific signalling Dublin, Ireland, .
	2017	Piouceau L, Rowan SC, Rochfort KD, Cornwell J, Cummins PM, McLoughlin P. (2017) 38th IUPS Congress Preserving lung function ex vivo prior to transplantation by perfusing with an optimized viscosity solution Rio de Janeiro, Brazil, .
	2016	Harper E, Forde H, Davenport C, Rochfort KD, Smith D, Cummins PM. (2016) 40th Annual Meeting of the Irish Endocrine Society Investigating the protective effect of TRAIL on RANKL-induced calcification using a vascular cell co-culture model [WINNER: Montgomery Medal - Best Poster Category] Belfast, Ireland, .
	2016	Forde H, Davenport C, Wallace RW, Rochfort KD, Murphy RP, Cummins PM, Smith D. (2016) Beaumont Hospital/RCSI Sheppard Prize Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) reduces endothelial oxidative stress in pro-atherogenic conditions [WINNER: Sheppard Prize - Best Poster Category] Dublin, Ireland, .
	2016	Forde H, Harper E, Davenport C, Rochfort KD, Cummins PM, Smith D (2016) 40th Annual Meeting of the Irish Endocrine Society Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) reduces oxidative stress in human aortic endothelial cells exposed to inflammatory stimuli Belfast, Ireland, .
	2012	Davenport C, Martin FA, Rochfort KD, Murphy RP, Cummins PM, Smith D (2012) 37th Annual Meeting of the Irish Endocrine Society The effects of inflammation, hyperglycemia and cyclic strain on OPG production in human aortic smooth muscle cells [WINNER: O'Donovan Medal - Best Speaker Category] Dublin, Ireland, .

Abstract

	Year	Publication
	2020	Kostyunina, D;Rochfort, KD;Cummins, PM;McLoughlin, P (2020) The Hypoxic Response of Shear Aligned Endothelial Cells: Approaching In Vivo Conditions. NEW YORK: ABST
	2019	Rochfort, KD;Carroll, LS;Barabas, P;Curtis, TM;Ambati, BK;Barron, N;Cummins, PM (2019) Hyperglycemic disruption of blood-retinal barrier phenotype in human retinal microvascular endothelial cells is mitigated with COMP-ANG1 treatment. LONDON: ABST
	2018	Harper, E;Rochfort, KD;Smith, D;Cummins, PM (2018) TRAIL protects from RANKL-induced calcification in the aortic endothelium via an anti-oxidant mechanism. LONDON: ABST
	2018	Rochfort, KD;Barabas, P;Carroll, LS;Curtis, TM;Ambati, BK;Barron, N;Cummins, PM (2018) COMP-ANG1 Stabilizes Hyperglycaemic Disruption of Blood-Retinal Barrier Phenotype in Human Retinal Microvascular Endothelial Cells. LONDON: ABST
	2017	Harper, E;Forde, H;Davenport, C;Rochfort, KD;Smith, D;Cummins, PM (2017) TRAIL protects from RANKL-induced calcification in an in vitro vascular co-culture model, in part via attenuation of NF-kappa B pro-calcific signalling. LONDON: ABST
	2016	Harper, E;Forde, H;Davenport, C;Rochfort, KD;Smith, D;Cummins, PM (2016) Investigating the protective effect of TRAIL on RANKL-induced calcification using a vascular cell co-culture model. LONDON: ABST

Review Articles

	Year	Publication
	2016	Forde H.;Harper E.;Davenport C.;Rochfort K.;Wallace R.;Murphy R.;Smith D.;Cummins P. (2016) The beneficial pleiotropic effects of tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) within the vasculature: A review of the evidence. REV [DOI]
	2016	Harper, E;Forde, H;Davenport, C;Rochfort, KD;Smith, D;Cummins, PM (2016) Vascular calcification in type-2 diabetes and cardiovascular disease: Integrative roles for OPG, RANKL and TRAIL. NEW YORK: REV [DOI]
	2015	Collins, LE;DeCourcey, J;di Luca, MS;Rochfort, KD;Loscher, CE (2015) An emerging role for SNARE protiens in dendritic cell function. LAUSANNE: REV [DOI]

Other Publication

	Year	Publication
	2021	Gopcevic, K.R.;Gkaliagkousi, E.;Nemcsik, J.;Acet, Ö.;Bernal-Lopez, M.R.;Bruno, R.M.;Climie, R.E.;Fountoulakis, N.;Fraenkel, E.;Lazaridis, A.;Navickas, P.;Rochfort, K.D.;Šatrauskienė, A.;Zupkauskienė, J.;Terentes-Printzios, D. (2021) Pathophysiology of Circulating Biomarkers and Relationship With Vascular Aging: A Review of the Literature From VascAgeNet Group on Circulating Biomarkers, European Cooperation in Science and Technology Action 18216. [Link] [DOI]

Honors and Awards

Date	Title	Awarding Body
01/12/2019	Emerging Talent Award	Faculty of Science and Health
01/10/2019	O'Donovan Medal	Irish Endocrine Society
01/10/2022	Basic Science Research Award	Irish Endocrine Society
01/12/2022	Enhancing the Student Experience	Faculty of Science and Health, DCU

Committees

	Committee	Function	From / To
	Frontiers in Cellular Neuroscience Editorial Committee		-
	Faculty of Science and Health Research Infrastructure Executive Committee		-
	Pharmaceutics Review Committee		-
	Biological Safety Committee		-

Employment

	Employer	Position	From / To
	University College Dublin	Post-Doctoral Researcher	01/01/2014 - 31/03/2016
	Dublin City University	Post-Doctoral Researcher	01/04/2016 - 30/06/2019

Reviews

	Journal	Role
	Scientific Reports	Reviewer
	Microvascular Research	Reviewer
	International Journal of Molecular Sciences	Reviewer
	ALTEX : Alternativen zu Tierexperimenten	Reviewer
	BRAIN RESEARCH	Reviewer
	Antioxidants	Reviewer
	Journal of Cerebral Blood Flow and Metabolism	Reviewer
	Neurochemical Research	Reviewer
	Diabetes and Vascular Disease Research	Reviewer
	Nutrients	Reviewer
	Cell Stress and Chaperones	Reviewer
	Cells	Reviewer
	Clinical Medicine Insights: Cardiology	Reviewer
	Pharmaceutics	Reviewer
	Experimental Eye Research	Reviewer
	Acta Neurobiologiae Experimentalis	Reviewer
	Frontiers in Physiology	Reviewer

Enterprise Engagement

Year	Engagement Type	Client	Description
2023	Equipment use/Access to Infrastructure	International Concussion and Head Injury Research Foundation	We are currently running working with the ICHIRF in providing access to equipment and technical expertise as part of an ongoing longitudinal study examining concussion in athletes.
2023	Invited talk/presentation	Ladies Gaelic Football Association	Stemming from our project investigating the prevalence and management of concussion in Ladies Gaelic Football, I routinely have delivered talks to coaches, players, parents, etc. on our results to date, while working with the governing body; the LGFA, to develop educational tools to improve awareness of this topic.
2023	Equipment use/Access to Infrastructure	Irish Horseracing Regulatory Board	As part of an on-going study examining biomarkers of concussion, the IHRB and ICHIRF are part of a collaboration with the School of Nursing, Psychotherapy and Community Health and the School of Health and Human Performance meausing miRNA markers in saliva samples.
2023	Consultancy	Rejuveron	The purpose of this consultancy is the target validation of a proprietary compound to be provided by the Client. Work to be conducted will include the culturing of endothelial cells, performing pharmacology experiments with and without gene knockdown, TEER measurements, as well as Western blotting and qPCR target validation. The work will be undertaken by RPO staff (Dr Janosch Heller and Dr Keith Rochfort). The work will be performed mainly in Laboratory XB11 in the Lonsdale Building, DCU. Equipment to be used belongs to the consultants’ research groups and Schools affiliated. The work does not involve dependencies.
2023	Other	Waterford Whiskey	As part of the Grain-4-Lab project, Waterford Distillery is an active partner and consultant in the workflows of the project

Outreach Activities

Year	Engagement Type	Organisation	Description
	Presentations/Talks to an external audience	DCU Healthy	Delivery of research-based information sessions to participants of Smoking Cessation Program run by DCU Healthy and the Northside Partnership
2023	Presentations/Talks to an external audience	LGFA	Development and delivery of educational webinars and video sessions aimed at improving concussion awareness in community games
2023	Educational Outreach/Public Engagement	Sci Fest	Judge within the competition
2023	Educational Outreach/Public Engagement	Kronos	Consultant for Kronos F1 racing team
2023	Educational Outreach/Public Engagement	IrEOES	Biology Mentor in the IREOES
2023	Educational Outreach/Public Engagement	IJSO	Country Coordinator for Irish branch of IJSO
2023	Educational Outreach/Public Engagement	VascAgeNet	Irish representative in COST Action CA18216 in developing resources to promote healthy ageing in the vasculature

Media

Title	Year	Type	Authors
Irish Endocrine Society 43rd Annual Meeting	2019	Newspaper article (online)	Mindo
DCU scientists awarded for creating more eco-friendly plastic from brewery waste	2022	Newspaper article (online)	Colman O'Sullivan
FutureProof	2022	Radio Interviews	Jonathan McCrea
High rate of concussion among Ladies GAA footballers, study finds	2022	Newspaper article (online)	Lynne Kelleher
DCU project tackling plastic use wins €2.4m in SFI challenge	2022	Newspaper article (online)	Leigh Mc Gowran
DCU scientists awarded for creating more eco-friendly plastic from brewery waste	2022	Other	Colman O'Sullivan

Research Interests

Healthy ageing and sustainability, with an focus on environmental factors which drive the pathological mechanisms and associated signaling events of vascular disease states, and developing diagnostic and therapeutic interventions towards such

Research Projects

Title	Role	Description	Start date	End date
Nanoparticle metabolite coronas: A neglected feature in nanoparticle interractions with biological matter	Co-supervisor	Nanotechnology is a rapidly evolving field aligning with industrial innovation and the generation of many promising applications. This is reflected in the increasing number of engineered nanomaterials and nanoparticles currently present in consumer and industrial products, which directly increases the incidence of exposure with risks towards human health and the environment. Studies focusing on cells and organisms have shown their toxic potential, however, mechanistically several aspects regarding toxicity of nanoparticles remain to be discovered. A critical parameter for the mediated toxic effects of nanoparticles lies in the interactions with biological systems occurring on the surface of nanoparticles, via the formation of coronas. Nanoparticle coronas are responsible for changes to their physicochemical properties but also very important for their interactions with living matter. Until now, the main interest in coronas has been focused on the proteins adsorbed on them, however, very few recent studies have been targeting a neglected parameter; the metabolite coronas. These small molecule coronas are also formed on the surface of nanoparticles and their implications on toxicity remain elusive. The proposed research will focus on developing methods and tools to characterise the molecular composition of the metabolite/small molecule coronas on nanoparticles, and study in a variety of in vitro and in vivo systems how this metabolite coating impacts the toxicity of nanoparticles from a mechanistic point. This project lies in the interphase of nanochemistry, cell biology and toxicology, combining holistic, molecular and biochemical methods. The in vitro aspect of this work will focus on the cellular uptake, the antimicrobial potential and the impact of nanoparticles on the inflammatory profile. Furthermore, using a well-established model organism in molecular ecotoxicology; the water flea, the in vivo toxicity will be explored. The role of coronas will be searched in detail mechanistically, from biological and chemical perspectives.	01/03/2022	01/03/2024
Mechanistic insight of nanocoronas on biological systems	Co-supervisor	Nano research evolved significantly the last decade together with great innovation. Nanomaterials are continuously present in products used daily, and as a result, a significant amount ends up in the environment. In relevance to nanotoxicity, literature is descriptive in the sources of nanoparticles in the environment, physicochemical alterations upon exposure to matter, and their adverse impacts on organisms [1]. Nanoparticles and nano-surfaces are known to absorb all kinds of molecules from their surroundings creating coronas, which are characteristic fingerprints of the environment they travelled to [2]. From a mechanistic point of view, the toxic potential of these nanocoronas is directly linked to the interactions of nanomaterials with biological matter. Till now, research has focused on protein nanocoronas, while there is only scarce evidence of a neglected small molecule or metabolite corona that could be formed [3,4]. The proposed research focuses on this unexplored feature of metabolite nanocoronas and its investigation in mechanistic toxicology. Combining a number of biological systems; bacteria, plants, cells and daphniids, a number of nanoparticles will be first screened and compared for their toxicity potential. Focusing on a specific type of nanomaterials, an in depth study of the ecotoxicological aspect of coating will be explored using sensitive holistic mass spectrometry approaches. The concept of this work is to highlight and show the existence first and following, to elevate the importance of a metabolite ecologically relevant nanocorona. Following, the overall aim it to develop sensitive metrics for the assessment of nanoparticle presence in actual water samples. Evidently, using the molecular (metabolic and protein) and phenotypic responses of daphniids as a key freshwater species, the aim is to use this key organism as an equivalent to “a canary in the goldmine” for early warning and prediction of nanopollution before it reaches precarious levels in actual water samples.	01/09/2022	30/09/2024
Grain-4-Lab	Co-supervisor	Grain-4-Lab will deliver prototype sustainable and compostable laboratory-grade bioplastic components produced by the valorisation of currently untapped waste-streams. In doing so Grain-4-Lab will promote the adoption of sustainable practices and the implementation of bioplastics in public sector institutions, along with setting up future supply-chains and routes to market in the Prize Phase. Grain-4-Lab will adopt a three-stream approach to solving the challenge: • Stream 1: Grain-4-Lab will utilising untapped waste-streams as feedstock for Lactic Acid (LA) production. A Lactic Acid Bacteria (LAB, Lactobacillus delbrueckii lactis) will efficiently (yields up to 96% w/w) convert sugars recovered from distilling waste products to LA. Next, a polymerisation step will produce poly-L-lactide (PLA) pellets, a compostable and recyclable bio-based plastic . • Stream 2: Grain-4-Lab will evaluate PLA prototype components constructed in-house through 3D-printing & injection moulding, reporting their chemical, biological, mechanical, and regulatory lab applicability. We will produce technical documentation benchmarking our material and components against plastic labware regulatory requirements. Where necessary Grain-4-Lab will investigate the application of plasticization and additives to tailor the properties of the polymer for specific laboratory applications[10] . Stream 3: Change management studies will be performed at policy level to provide feasible pathways for change of practice. During the Prize Phase Grain-4-Lab consumables will be tested in third-level science laboratories. Adoption protocols and proof-of-concept documentation will be created to prove and publish a sustainable laboratory adoption framework.	01/03/2022	31/03/2024
Investigation of the mechanisms of COVID-19 associated neurological disease	Co-supervisor	This study will investigate the mechanisms by which SARS-CoV-2 causes neurological disease, using human tissue and cells, and state-of-the-art 3D in vitro model systems. We will profile ACE-2 expression in human brain tissue and in primary CNS cells as well as immune cell types that are known to traffic to the brain in inflammatory conditions. We will investigate whether cells of the CNS are direct targets for viral infection. We will model the inflammatory microenvironment in severe COVID-19 disease and investigate the ability of SARS-CoV-2 to invade the brain across the BBB and blood-CSF barriers, and the subsequent impact upon homeostasis of cells within the brain parenchyma. We will expose brain endothelial cells cultured under physiological flow to SARS-CoV-2 or individual viral proteins in the context of the inflammatory microenvironment and investigate the pathogenesis of the cerebrovascular damage observed in patients with COVID-19-related neurological disease. Finally, we will evaluate a range of potential therapeutic interventions for their ability to modulate or reverse pathological changes observed. This highly novel, translational approach uses a range of physiologically relevant model systems and human tissue to elucidate the exact nature of the neurological changes reported in COVID-19 patients as well as potential therapeutic interventions that may improve patient outcomes.	01/01/2021	01/03/2022
Development of a novel, multi-level strategy to enhance concussion identification and appropriate management in the community sport of Ladies Gaelic Football	Co-Principal Investigator	Approximately 10,000 people sustain a traumatic brain injury (TBI) in Ireland each year, 90% of which involve concussion[7]. Although generally perceived to be a “mild” injury, its consequences can be severe, and occasionally fatal. 10-15% of patients suffer from chronic symptoms and long-term disability[8], while repeated concussions have been linked to progressive neurodegenerative diseases in later life[9]. Sportspeople are at an increased risk of sustaining a concussion[8], and over half of GAA players report a history of sport-related concussion (SRC)[9]. The potentially devastating consequences, combined with the substantial financial burden of TBI (Acquired Brain Injury Ireland (ABI Ireland) have an annual expenditure of €12,964,907), highlight the urgent need for better SRC management practices. Effective SRC management is hindered by unique diagnostic challenges, particularly its non-specific signs/symptoms, and lack of objective clinical measures. The Sport Concussion Assessment Tool 5th Edition (SCAT5) is the current “gold-standard” diagnostic test, however it is limited by its reliance on self-reported symptoms[?]. Consequently, contentious decisions involving concussed players are common in sport, emphasising the urgent need for an objective and quantifiable diagnostic method. The blood brain barrier (BBB) is a highly specialised membrane controlling the exchange of substances between the cerebral and peripheral circulations. TBI-driven increases in BBB permeability enable markers of cerebrovascular damage to enter the peripheral bloodstream, presenting them for detection. A viable biomarker/biomarker panel would represent a significant breakthrough in sports medicine, as it would facilitate the development of objective diagnostic and management guidelines, greatly enhancing player welfare. This project aims to (i) profile the in-vitro response of human neurovascular cells to comparative levels of force observed in SRC using a tension system (ii) investigate established and prospective markers of neurovascular damage in the blood among adult GAA players, and (iii) compare findings from (i) and (ii) to improve the understanding of the pathological mechanisms at play in SRC, with a focus on improving the current clinical management of the condition.	01/03/2019	01/03/2022
Investigation of the mechanisms of COVID-19 associated neurological disease	DCU PI		01/12/2020	31/07/2021
Screening of therapeutic compounds for treatment of blood-brain barrier disorders	Co-lead	The purpose of this consultancy is the target validation of a proprietary compound to be provided by the Client. Work to be conducted will include the culturing of endothelial cells, performing pharmacology experiments with and without gene knockdown, TEER measurements, as well as Western blotting and qPCR target validation. The work will be undertaken by RPO staff (Dr Janosch Heller and Dr Keith Rochfort). The work will be performed mainly in Laboratory XB11 in the Lonsdale Building, DCU. Equipment to be used belongs to the consultants’ research groups and Schools affiliated. The work does not involve dependencies.	01/03/2023	01/03/2024
Super-resolution imaging to uncover microRNA control of blood -brain-barrier breakdown in epilepsy	Co-supervisor	Epilepsy is a chronic disease of the brain which accounts for a significant proportion of global disease burden, affecting between 4 and 10 per 1000 people. The disease is characterized by recurring bursts of electrical activity or ‘seizures’, affecting brain function. Common anti-epileptic drugs are ineffective in about a third of patients, highlighting the need for new treatment options. All anti-epileptic drugs target neurons, the cells that generate the electrical signals that are needed for information processing in the brain. However, other cell types in the brain are also affected in epilepsy. One such cell type are astrocytes (literally meaning star-cells). These cells are essential for the correct functioning of the brain and the blood-brain barrier, holding neurons in place, helping neurons with the information processing, and regulating waste clearance from the brain. All these functions are disturbed in the epileptic brain. Hence, targeting astrocytes could be a new therapeutic strategy to prevent seizure generation and damage to the brain. Here, I will use a combination of cell and tissue models as well as a rodent model of epilepsy to investigate changes in the presence of small molecules called microRNAs that regulate protein expression levels. MicroRNA changes in neuronal cells have already been studied during epilepsy, and blocking their functions is currently being trialled as therapy. By targeting microRNAs with drugs, I aim to improve both astrocyte function the epileptic mouse brain. I will use novel microscopy approaches to visualise the impact of my treatment. This translational project has the potential to improve our approach to treatment-resistant epilepsy by targeting astrocyte functions that are disrupted in the epileptic brain.	01/09/2021	01/09/2025
To elucidate the effect of semaglutide on a three-dimensional model of the blood retinal barrier in a diabetic setting	Lead	Since the initial observation that higher rates of retinopathy complications occurred in patients treated with semaglutide in the seminal SUSTAIN-6 and PIONEER-6 studies there has been concern over the revolutionary drug’s safety profile. Since then, a direct effect of semaglutide on the retina has still not been excluded. Given the recent influx of GLP-1 agonists to the market, an exploration of this purported association is increasingly necessary. Our proposed study will clarify the direct and indirect effects of semaglutide on cell types of the retinal microvasculature using an in vitro human model of diabetic retinopathy. This will expedite our understanding of the glucose lowering agent in a microvascular environment, while also delineating the patients for whom this drug may be unsuitable if a negative correlation between drug use and indices of retinopathy are identified.	01/10/2022	01/10/2023

Contract Researchers

	Researcher Name	Project	Funding Body
	Róisín Leahy	Development of a novel, multi-level strategy to enhance concussion identification and appropriate management in the community sport of Ladies Gaelic Football

Current Postgraduate Students

Student Name	Degree	Supervision
Aleksejenko ,Natalija	PhD-track	Supervisor
Donnelly ,Niamh	PhD-track	Supervisor
Kakavas ,Dimitrios	PhD-track	Supervisor

Internal Collaborators

Type	Name	Company	Role
Internal	Dr. Phil Cummins	School of Biotechnology, Dublin City University	Academic
Internal	Dr. Enda Whyte	School of Health and Human Performance, Dublin City University	Academic
Internal	Dr. Siobhán O'Connor	School of Health and Human Performance, Dublin City University	Academic

External Collaborators

Type	Name	Company	Role
External	Dr. Bala Ambati	Pacific Clear Vision Institute	Academic
External	Dr. Lara Carroll	Moran Eye Center, University of Utah	Academic
External	Dr. Diarmuid Smith	Beaumont Hospital	Other
External	Prof. Tim Curtis	School of Medicine, Dentistry, and Biomedical Sciences, Queen's University Belfast	Academic
External	Dr. Hannah Forde	Beaumont Hospital	Other
External	Prof. Paul McLoughlin	University College Dublin	Academic
External	Dr. Peter Barabas	School of Medicine, Dentistry, and Biomedical Sciences, Queen's University Belfast	Academic

Modules Coordinated

	Term	Title	Subject
	2022	Clinical Pharmacology for Nursing Practise	NS204
	2022	Human Genetics & Cell Biology	NS233