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Dr. John Mulvihill

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Biography

Throughout my career I have endeavoured to be a multidisciplinary researcher. This is evidenced by my first-class honours degree in mechanical engineering where I specialised in fluid dynamics of kidney dialysis. From this work I was awarded a scholarship from the Irish Research Council to fund my PhD in the area of biomedical engineering and was awarded a national innovative Student Engineer award by Engineers Ireland.

During my PhD, I developed a wide variety of techniques to mechanically, structurally, and biologically characterise diseased cardiovascular tissue. These methodologies have led to the publication of 9-articles and 4-reviews in first quartile journals in areas such as urology, gastrointestinal tissues and aortic aneurysms. It was clear from the conclusion of my PhD work that I needed experience on the effect of mechanics on cell function, behaviour and morphology. Accordingly, I was successful in my application for a Marie-Curie co-fund fellowship based in Prof. Ethier's lab in the Georgia Institute of Technology. During this time, I gained experience in cell culture, biochemistry and immunostaining techniques. My particular focus was on the effect of mechanical deformations on astrocytes, a key cell line in optic, spinal and cortical function, resulting in 4-articles [14-17] collaborating with researchers in Cardiff University and Imperial College London.

It is from this work that, at this stage in my career, I want to investigate the role of astrocytes in concussion and blood brain barrier (BBB) function, an area of societal and scientific importance. My current scientific activities are based on two strands; concussion and astrocytoma. The link between the two is the role of astrocytes in the alteration of the BBB and what protein markers are secreted into the bloodstream post-injury or disease. With this in mind, my aim is to build a platform to study these conditions using cells isolated from porcine tissue in either healthy or ‘injured' conditions. I want to integrate expertise in mechanics from my PhD research to develop an injury model for concussion and examine the effects this has on the mechanical, biological and structural characterisation of the tissue. From my postdoctoral research experience, I want to examine the effects that this injury has on the role astrocytes play in the maintenance and subsequent disruption of the BBB function. More importantly, I want to identify and measure the proteins that cross the BBB when the brain is injured in order to elucidate these key protein markers for post-concussion identification. By examining these cell-cell interactions I can better understand the effect that introducing injured/diseased cells into this model can have on the BBB integrity and the proteins which traverse into the blood stream. With a grant like the Science Foundation Ireland Career Development Award I will be able to build a platform of research to collaborate with sport organisations to aid our understanding of concussion.

Research Interests

Globally an estimated 40 million people are affected annually by Traumatic Brian Injury (TBI). The cumulative cost of TBIs in the US alone is $76.5 billion, 80% of which are defined as concussion. Concussion is a mild form of traumatic injury to the brain where repeated and undetected concussions can lead to permanently altered brain function. Consequently, the burden of mortality and morbidity that concussion imposes on society makes this condition a critical public health problem. Currently there are no official statistics for the number of people living in Ireland with a brain injury but it has been estimated that between 8,000-10,000 people sustain concussions annually.
Concussion awareness is increasing almost daily in most mainstream sports. However, there is currently no scientific test for concussion – only a subjective head injury assessment. The goal of our research is to study the mechanism of this injury at a cellular level to take steps towards a device to diagnose it. In normal conditions, brain-derived proteins are prevented from entering the bloodstream by an almost completely impermeable cellular wall – the blood-brain barrier. However, post-concussion, this barrier malfunctions and allows these proteins to enter the bloodstream. These proteins could potentially be used to diagnose concussion - recent research has pointed to a number of key proteins that change in concentration in the blood of patients with concussion. However, they have found it difficult to outline the markers, as patients may have suffered from other injuries, such as broken bones.
Thus far, researchers have failed to solve for how these proteins enter the bloodstream and thus, cannot attribute their presence directly to concussion. The aim of this proposed research is to study the mechanisms of how these proteins cross into the bloodstream. Ultimately we hope to aid in the identification of biomarkers to help a blood based diagnostic method to allow for accurate, immediate and irrefutable diagnosis of a concussive injury.

Professional Activities

Award

  • 2014 - ELEVATE Marie-Curie Fellowship
  • 2012 - New Foundations Grant
  • 2009 - Innovative Student Engineer Award
  • 2009 - Irish Research Council EMBARK PhD Scholarship

Education

  • 2013 University of Limerick - PhD

Committee

  • Science and Engineering Ethics Committee ,
  • School of Engineering Teaching and Learning Team,
  • School of Engineering Athena Swan Committee,

Publications

Book Chapter

2018

Biomaterials and Regenerative Medicine in Urology
Davis, NF and Cunnane, EM and Quinlan, MR and Mulvihill, JJ and Lawrentschuk, N and Bolton, DM and Walsh, MT
Advances in experimental medicine and biology DOI: 10.1007/5584_2017_139

Conference Publication

2016

The Association for Research in Vision and Ophthalmology
Mulvihill, J.J.E., Schildmeyer, L.A., Raykin, J., Snider, E., Chinoy, K., Kelly, D.J. and Ethier, C.R.,

2013

ASME. Summer Bioengineering Conference
Mulvihill JJ, Cunnane EM, Kavanagh EE, Walsh MT.
DOI: 10.1115/SBC2013-14693.

2013

Carotid Plaque Composition and Mechanism of Behaviour
McHugh, S,Mulvihill, J,Cunnane, E,Kavanagh, E,Walsh, S,Walsh, M

2011

ASME 2011 Summer Bioengineering Conference
Mulvihill JJ, O'Donnell MR, O'Connell BM, Walsh MT.
DOI: 10.1115/SBC2011-53440.

Peer Reviewed Journal

2020

Drug delivery across the blood-brain barrier: recent advances in the use of nanocarriers
Mulvihill J.;Cunnane E.;Ross A.;Duskey J.;Tosi G.;Grabrucker A.
Nanomedicine (London, England) DOI: 10.2217/nnm-2019-0367

2019

Standardization of research methods employed in assessing the interaction between metallic-based nanoparticles and the blood-brain barrier: Present and future perspectives.
Ross AM;Mc Nulty D;O'Dwyer C;Grabrucker AM;Cronin P;Mulvihill JJE;
Journal Of Controlled Release DOI: 10.1016/j.jconrel.2019.01.022

2018

Development of a Platform for Studying 3D Astrocyte Mechanobiology: Compression of Astrocytes in Collagen Gels
Mulvihill, John J. E.,Raykin, Julia,Snider, Eric J.,Schildmeyer, Lisa A.,Zaman, Irsham,Platt, Manu O.,Kelly, Daniel J.,Ethier, C. Ross
Annals of Biomedical Engineering

2018

Tissue engineered extracellular matrices (ECMs) in urology: Evolution and future directions
Davis, N.F.,Cunnane, E.M.,O'Brien, F.J.,Mulvihill, J.J.,Walsh, M.T.
The Surgeon

2018

Digital and Mechanical Characterization of Ureteral Stent Luminal Reduction in Response to Extrinsic Compression Forces
Davis, NF;Mulvihill, JJE;Lynch, JJ;Browne, E;Bolton, DM;Jack, GS;Walsh, MT
Journal Of Endourology DOI: 10.1089/end.2018.0573

2018

Urinary Bladder vs Gastrointestinal Tissue: A Comparative Study of Their Biomechanical Properties for Urinary Tract Reconstruction
Davis, NF,Mulvihill, JJE,Mulay, S,Cunnane, EM,Bolton, DM,Walsh, MT
Urology DOI: 10.1016/j.urology.2017.11.028

2018

The Role of Stem Cells for Reconstructing the Lower Urinary Tracts.
Davis NF;Cunnane EM;Mulvihill JJ;Quinlan MR;Bolton DM;Walsh MT;Jack GS;
Current Stem Cell Research & Therapy DOI: 10.2174/1574888X13666180426113907

2017

Reduced plaque size and inflammation in the APP23 mouse model for Alzheimer’s disease after chronic application of polymeric nanoparticles for CNS targeted zinc delivery
Vilella, Antonietta,Belletti, Daniela,Sauer, Ann Katrin,Hagmeyer, Simone,Sarowar, Tasnuva,Masoni, Martina,Stasiak, Natalia,Mulvihill, John J.E.,Ruozi, Barbara,Forni, Flavio,Vandelli, Maria Angela,Tosi, Giovanni,Zoli, Michele,Grabrucker, Andreas M.
Journal of Trace Elements in Medicine and Biology

2017

Deformation of the Lamina Cribrosa and Optic Nerve Due to Changes in Cerebrospinal Fluid Pressure
Feola, Andrew J.,Coudrillier, Baptiste,Mulvihill, John,Geraldes, Diogo M.,Vo, Nghia T.,Albon, Julie,Abel, Richard L.,Samuels, Brian C.,Ethier, C. Ross
Investigative Ophthalmology & Visual Science

2017

Zinc Binding to S100B Affords Regulation of Trace Metal Homeostasis and Excitotoxicity in the Brain
Hagmeyer, Simone and Cristóvão, Joana S. and Mulvihill, John J. E. and Boeckers, Tobias M. and Gomes, Cláudio M. and Grabrucker, Andreas M.
Frontiers In Molecular Neuroscience DOI: 10.3389/fnmol.2017.00456

2017

A modified gelatin zymography technique incorporating total protein normalization
Raykin, Julia,Snider, Eric,Bheri, Sruti,Mulvihill, John,Ethier, C. Ross
Analytical Biochemistry

2016

Development of a platform for studying astrocyte mechanobiology in 3D culture
Mulvihill, John Joseph Eugene,Schildmeyer, Lisa A,Raykin, Julia,Snider, Eric,Chinoy, Kavita,Kelly, Daniel J,Ethier, C Ross
Investigative Ophthalmology & Visual Science

2016

Mechanical properties and composition of carotid and femoral atherosclerotic plaques: A comparative study
Cunnane, Eoghan M.,Mulvihill, John J.E.,Barrett, Hilary E.,Hennessy, Mairead M.,Kavanagh, Eamon G.,Walsh, Michael T.
Journal of biomechanics

2016

Effects of Peripapillary Scleral Stiffening on the Deformation of the Lamina Cribrosa
Coudrillier, Baptiste,Campbell, Ian C.,Read, A. Thomas,Geraldes, Diogo M.,Vo, Nghia T.,Feola, Andrew,Mulvihill, John,Albon, Julie,Abel, Richard L.,Ethier, C. Ross
Investigative Ophthalmology & Visual Science

2015

Determining the influence of calcification on the failure properties of abdominal aortic aneurysm (AAA) tissue
O’Leary, Siobhan A.,Mulvihill, John J.,Barrett, Hilary E.,Kavanagh, Eamon G.,Walsh, Michael T.,McGloughlin, Tim M.,Doyle, Barry J.
Journal of the Mechanical Behavior of Biomedical Materials

2015

Simulation of human atherosclerotic femoral plaque tissue: the influence of plaque material model on numerical results
Cunnane, Eoghan M.,Mulvihill, John JE,Barrett, Hilary E.,Walsh, Michael T.
BioMedical Engineering OnLine

2015

Characterising human atherosclerotic carotid plaque tissue composition and morphology using combined spectroscopic and imaging modalities
Barrett, Hilary E.,Mulvihill, John J.,Cunnane, Eoghan M.,Walsh, Michael T.
BioMedical Engineering OnLine

2015

Mechanical, biological and structural characterization of human atherosclerotic femoral plaque tissue
Cunnane, E.M.,Mulvihill, J.J.E.,Barrett, H.E.,Healy, D.A.,Kavanagh, E.G.,Walsh, S.R.,Walsh, M.T.
Acta Biomaterialia

2014

Uniaxial tensile testing approaches for characterisation of atherosclerotic plaques
Walsh, M.T.,Cunnane, E.M.,Mulvihill, J.J.,Akyildiz, A.C.,Gijsen, F.J.H.,Holzapfel, G.A.
Journal of biomechanics

2014

Computational approaches for analyzing the mechanics of atherosclerotic plaques: A review
Holzapfel, Gerhard A.,Mulvihill, John J.,Cunnane, Eoghan M.,Walsh, Michael T.
Journal of biomechanics

2013

On the mechanical behaviour of carotid artery plaques: the influence of curve-fitting experimental data on numerical model results
Mulvihill, John J.,Walsh, Michael T.
Biomechanics and Modeling in Mechanobiology

2013

Mechanical, biological and structural characterization of in vitro ruptured human carotid plaque tissue
Mulvihill, J.J.,Cunnane, E.M.,McHugh, S.M.,Kavanagh, E.G.,Walsh, S.R.,Walsh, M.T.
Acta Biomaterialia

2012

Development of an experimental model of the carotid bifurcation using electrically conductive silicone: an introduction to the incorporation of baroreceptor function within a mimetic model of the carotid artery
Mulvihill, John J.,Cunnane, Eoghan M.,O’Connell, Barry M.,Walsh, Michael T.
International Journal of Nano and Biomaterials