Dr Adjanie Patabendige

Dr Adjanie Patabendige

NSW Health EMC Fellow

School of Biomedical Sciences and Pharmacy

Career Summary

Biography

Biography

Dr Patabendige is a research fellow with significant research expertise in cerebrovascular biology, and in particular, studying the blood-brain barrier (BBB, the specialised physiological barrier that protects the brain from blood-borne toxins and pathogens, and regulates molecular traffic between the blood and the brain) in health and disease. She received her PhD from King's College London (University of London), UK under the mentorship of Prof Joan Abbott. During her PhD, she developed a porcine BBB model that mimics the in vivo BBB closely. This is one of the most robust and reproducible primary BBB models currently available, and is being used by many academics and pharmaceutical companies for drug screening and functional studies. Following her PhD, she spent a short period working with pharmaceutical industry partners before moving to the University of Liverpool, UK.

Her postdoctoral research at Liverpool was focused on developing a human BBB model to study viral encephalitis. Here she used containment level 3 flaviviruses to investigate the mechanisms of neuroinvasion across the human BBB and the pro-inflammatory cytokine response on the brain endothelium. In 2012, Dr Patabendige was awarded one of the inaugural David Sainsbury Fellowships from the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs, UK) for early career researchers. The University of Liverpool awarded a Tenure-Track Fellow position to Dr Patabendige in 2014 recognising her potential of becoming a future research leader. Dr Patabendige relocated to Australia in 2014 to continue her fellowship with collaborators based in Melbourne. In 2016, recognising her expertise in BBB and cerebrovascular biology, Dr Patabendige was recruited to the Translational Stroke Research Group at the University of Newcastle to head a laboratory team working on an NHMRC funded project on intracranial pressure (ICP) and hypothermia treatment for stroke. Dr Patabendige was awarded an Early-Mid Career Fellowship from the NSW Ministry of Health in 2018 to lead a translational research project in stroke to understand the the early neurological deterioration in ischaemic stroke patients.

Current research interests

Understanding the pathophysiology of ischaemic stroke

Dr Patabendige is interested in investigating the mechanisms involved in the pathophysiology of impaired brain fluid homeostasis in neurological diseases such as stroke and brain trauma. Disruption of brain fluid dynamics can be life threatening, as this leads to an elevated ICP. Dr Patabendige’s current research within the Translational Stroke Research group involves the use of a range of preclinical and in vitro models to explore potential treatment strategies to reduce the ICP elevation post ischaemic stroke. In addition, she's using a novel non-invasive method to measure ICP in stroke patients with advanced medical imaging to understand the underlying disease pathophysiology in early neurological deterioration in mild to moderate strokes.

Development and establishment of novel BBB models

Continuing on her success in developing in vitro BBB models for drug screening, Dr Patabendige is currently establishing a BBB model to understand the detailed cellular and molecular mechanisms of stroke pathophysiology, to identify new disease biomarkers and quantify brain penetration of neuroprotective drugs across the diseased BBB. 

Industry Engagement

Dr Patabendige has experience engaging with major pharmaceutical industry partners, including UCB Belgium, Syngenta, as well as SMEs in UK on collaborative projects on CNS drug discovery studies. Her current industry collaborations are funded by the Australian Academy of Technology and Engineering (ATSE)

Teaching

HUBS3403: Neuroscience - Stroke I & III

PHAR3103: Mental and Neurological Health - Trauma and intracranial pressure control

Available for PhD, Masters and honours project supervision

Administrative

Institutional Biosafety Committee (IBC)


Qualifications

  • Doctor of Philosophy, Kings College - London
  • Bachelor of Science (Neuroscience), Kings College - London

Keywords

  • Blood-brain barrier
  • Cerebrospinal fluid
  • Cerebrovascular biology
  • Choroid plexus
  • Encephalitis
  • Flavivirus
  • Neuroinflammation
  • Stroke
  • in vitro models

Fields of Research

Code Description Percentage
110904 Neurology and Neuromuscular Diseases 40
111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified 10
110999 Neurosciences not elsewhere classified 50

Grant Reviews

Year Grant Amount
2014 Project grant
International - Competitive - 3IFA, International - Competitive - 3IFA
$675,000
2014 Recherches Partenariales et Innovation Biomédicale (RPIB: Partnership Research and Biomedical Innovation)
International - Competitive - 3IFA, International - Competitive - 3IFA
$590,000
2013 Career Development Awards
International - Competitive - 3IFA, International - Competitive - 3IFA
$1,170,000
2012 Project grant - Neurosciences & Mental Health Board
International - Competitive - 3IFA, International - Competitive - 3IFA
$535,000
2012 Project grant - Neurosciences & Mental Health Board
International - Competitive - 3IFA, International - Competitive - 3IFA
$880,000
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Publications

For publications that are currently unpublished or in-press, details are shown in italics.


Chapter (1 outputs)

Year Citation Altmetrics Link
2014 Solomon T, Patabendige A, Whitley RJ, 'Arthropod-borne viral encephalitidesm', Infections of the Central Nervous System: Fourth Edition (2014)
Citations Scopus - 4

Journal article (9 outputs)

Year Citation Altmetrics Link
2018 Patabendige A, Michael BD, Craig AG, Solomon T, 'Brain microvascular endothelial-astrocyte cell responses following Japanese encephalitis virus infection in an in vitro human blood-brain barrier model', Molecular and Cellular Neuroscience, 89 60-70 (2018) [C1]

© 2018 The Authors Japanese encephalitis virus (JEV) remains a leading cause of encephalitis, globally, which continues to grow in importance despite the availability of vaccines.... [more]

© 2018 The Authors Japanese encephalitis virus (JEV) remains a leading cause of encephalitis, globally, which continues to grow in importance despite the availability of vaccines. Viral entry into the brain can occur via the blood-brain barrier (BBB), and inflammation at the BBB is a common final pathway in many brain infections. However, the role of the BBB during JEV infection and the contribution of the endothelial and astrocytic cell inflammation in facilitating virus entry into the brain are incompletely understood. We established a BBB model using human brain endothelial cells (HBECs) and human astrocytes. HBECs are polarised, and therefore the model was inoculated by JEV from the apical side to simulate the in vivo situation. The effects of JEV on the BBB permeability and release of inflammatory mediators from both apical and basolateral sides, representing the blood and the brain side respectively were investigated. JEV infected HBECs with limited active virus production, before crossing the BBB and infecting astrocytes. Control of JEV production by HBECs was associated with a significant increase in permeability, and with elevation of many host mediators, including cytokines, chemokines, cellular adhesion molecules, and matrix metalloproteases. When compared to the controls, significantly higher amounts of mediators were released from the apical side as opposed to the basolateral side. The increased release of mediators over time also correlated with increased BBB permeability. Treatment with dexamethasone led to a significant reduction in the release of interleukin 6 (IL6), C-C motif chemokine ligand 5 (CCL5) and C-X-C motif chemokine ligand 10 (CXCL10) from the apical side with a reduction in BBB disruption and no change in JEV production. The results are consistent with the hypothesis that JEV infection of the BBB triggers the production of a range of host mediators from both endothelial cells and astrocytes, which control JEV production but disrupt BBB integrity thus allowing virus entry into the brain. Dexamethasone treatment controlled the host response and limited BBB disruption in the model without increasing JEV production, supporting a re-investigation of its use therapeutically.

DOI 10.1016/j.mcn.2018.04.002
2015 Ferguson MC, Saul S, Fragkoudis R, Weisheit S, Cox J, Patabendige A, et al., 'Ability of the Encephalitic Arbovirus Semliki Forest Virus To Cross the Blood-Brain Barrier Is Determined by the Charge of the E2 Glycoprotein', JOURNAL OF VIROLOGY, 89 7536-7549 (2015) [C1]
DOI 10.1128/JVI.03645-14
Citations Scopus - 14Web of Science - 13
2014 Patabendige A, Joan Abbott N, 'Primary porcine brain microvessel endothelial cell isolation and culture', Current Protocols in Neuroscience, 2014 3.27.1-3.27.17 (2014)

© 2014 by John Wiley & Sons, Inc. Cell culture models of the blood-brain barrier (BBB) are useful tools to study the functionality of the BBB in health and disease. Several ... [more]

© 2014 by John Wiley & Sons, Inc. Cell culture models of the blood-brain barrier (BBB) are useful tools to study the functionality of the BBB in health and disease. Several good in vitro BBB models are available from different species. However, most brain endothelial cells lose some of their in vivo BBB phenotype in culture. Porcine brain endothelial cells (PBECs) tend to retain most of their in vivo BBB characteristics and usually give higher transendothelial electrical resistance (TEER, representing functional well-developed tight junctions) compared to brain endothelial cells from other species. The protocol described in this unit gives detailed instructions for isolation and culture of PBECs from fresh porcine brains. This porcine BBB model generates high TEER without the need for co-culture with astrocytes. However, astrocyte-derived factors can be introduced to the system through the use of astrocyte-conditioned medium or co-culture with astrocytes, which may be necessary for further enhancing the BBB phenotype for certain complex studies.

DOI 10.1002/0471142301.ns0327s69
Citations Scopus - 6
2013 Patabendige A, Skinner RA, Abbott NJ, 'Establishment of a simplified in vitro porcine blood-brain barrier model with high transendothelial electrical resistance', BRAIN RESEARCH, 1521 1-15 (2013)
DOI 10.1016/j.brainres.2012.06.057
Citations Scopus - 70Web of Science - 58
2013 Patabendige A, Skinner RA, Morgan L, Abbott NJ, 'A detailed method for preparation of a functional and flexible blood-brain barrier model using porcine brain endothelial cells', BRAIN RESEARCH, 1521 16-30 (2013)
DOI 10.1016/j.brainres.2013.04.006
Citations Scopus - 45Web of Science - 42
2012 Patabendige A, 'The Value of In Vitro Models of the Blood-Brain Barrier and Their Uses', ATLA-ALTERNATIVES TO LABORATORY ANIMALS, 40 335-338 (2012)
Citations Scopus - 6Web of Science - 5
2012 Patabendige A, 'Toward a Humanised Alternative to the Use of Laboratory Animals for Blood-Brain Barrier Research', ATLA-ALTERNATIVES TO LABORATORY ANIMALS, 40 P12-P13 (2012)
2010 Abbott NJ, Patabendige AAK, Dolman DEM, Yusof SR, Begley DJ, 'Structure and function of the blood-brain barrier', NEUROBIOLOGY OF DISEASE, 37 13-25 (2010)
DOI 10.1016/j.nbd.2009.07.030
Citations Scopus - 1562Web of Science - 1443
2008 Abbott NJ, Dolman DEM, Patabendige AK, 'Assays to Predict Drug Permeation Across the Blood-Brain Barrier, and Distribution to Brain', CURRENT DRUG METABOLISM, 9 901-910 (2008)
DOI 10.2174/138920008786485182
Citations Scopus - 44Web of Science - 37
Show 6 more journal articles

Conference (13 outputs)

Year Citation Altmetrics Link
2017 Patabendige A, MacKovski N, Hood R, Pepperall D, Spratt N, 'Real-time measurement of cerebrospinal fluid production post-stroke. 12th International Conference on Cerebral Vascular Biology.', Melbourne, Australia (2017)
Co-authors Neil Spratt
2015 Patabendige A, Michael B, Nicolazzo J, Mackenzie J, Craig A, Solomon T, 'Interactions between Japanese encephalitis virus and the blood-brain barrier: inflammation and a role for steroids? 8th Australasian Virology Society meeting. Australia.', Hunter Valley, NSW, Australia (2015)
2014 Patabendige A, Defres S, Keller S, Vidyasagar R, Michael B, Das K, et al., 'THE BBB IN ENCEPHALITIS: INFLAMMATION & A ROLE FOR STEROIDS?', JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, Cardiff, WALES (2014)
DOI 10.1136/jnnp-2014-309236.124
2014 McQuaid C, Jacob A, Patabendige A, 'EFFECT OF TYSABRI AND AQP4-IGG ON AN IN-VITRO MODEL OF BBB', JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, Cardiff, WALES (2014)
DOI 10.1136/jnnp-2014-309236.162
2013 Patabendige A, Michael B, Solomon T, 'Japanese encephalitis virus infection disrupts the blood-brain barrier by inducing a strong pro-inflammatory host response. 7th Australasian Virology Society meeting. New Zealand.', Queenstown, New Zealand (2013)
2012 Patabendige A, 'Mechanisms of Japanese encephalitis virus entry through the blood-brain barrier. Emerging viruses: disease models and strategies for vaccine development. USA.', Galveston, Texas, USA (2012)
2012 Patabendige A, 'Understanding the mechanisms of blood-brain barrier disruption caused by Japanese encephalitis virus in an in vitro human model. 2nd UK & Ireland early career blood-brain barrier symposium.', Liverpool, UK (2012)
2010 Patabendige A, Solomon T, 'A human ex-vivo blood-brain barrier model to study viral encephalitis. 2nd International Conference on Neuroinfection & Worldwide Impact. Reunion Island.', Saint-Denis, Reunion Island (2010)
2009 Patabendige A, Abbott NJ, 'Characterisation of a simplified in vitro blood-brain barrier model using porcine brain endothelial cells for drug permeability assays. 12th International Symposium: Signalling at Blood-Brain and Blood-Retinal Barriers. UK.', UCL, London, UK (2009)
2007 Patabendige A, Nixon G, Abbott NJ, 'Optimisation and validation of a robust in vitro porcine brain endothelial cell model for studying blood-brain barrier permeability and functionality. 7th International Conference on Cerebral Vascular Biology. Canada.', Ottawa, Canada (2007)
2005 Patabendige A, Youdim KA, Abbott NJ, 'Ability of phenolic compounds to protect the blood-brain barrier against oxidative stress. Physiological Society Main Meeting. UK.', Proceedings of The Physiological Society, King's College London (2005)
2004 Patabendige A, 'Interaction of flavonoids and other phenolic compounds with the blood-brain barrier: permeability, transport and protection against oxidative stress. 7th International Symposium on Signal Transduction in the Blood-Brain Barriers. Germany.', Potsdam, Germany (2004)
2004 Abbott NJ, Youdim KA, Patabendige A, Rice-Evans C, Begley DJ, Qaizer MZ, 'Interaction of flavonoids with the blood-brain barrier: permeability, transport and protection against oxidative stress', Tilton, USA (2004)
Show 10 more conferences

Other (1 outputs)

Year Citation Altmetrics Link
2015 Ferguson M, Saul S, Fragkoudis R, Weisheit S, Cox J, Patabendige A, et al., 'Semliki Forest virus strain SFV6, complete genome', Accession No. KT009012.1, Semliki Forest virus strain SFV6, complete genome. Bethesda, USA: National Library of Medicine (US), National Center for Biotechnology Information (2015)
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Grants and Funding

Summary

Number of grants 5
Total funding $1,657,670

Click on a grant title below to expand the full details for that specific grant.


Highlighted grants and funding

Steps Towards Understanding and Preventing Early Neurological Deterioration in Ischaemic Stroke (STUPENDIS)$577,670

Funding body: NSW Ministry of Health

Funding body NSW Ministry of Health
Project Team Doctor Adjanie Patabendige
Scheme Early-Mid Career Fellowships
Role Lead
Funding Start 2018
Funding Finish 2021
GNo G1701366
Type Of Funding Other Public Sector - State
Category 2OPS
UON Y

20181 grants / $577,670

Steps Towards Understanding and Preventing Early Neurological Deterioration in Ischaemic Stroke (STUPENDIS)$577,670

Funding body: NSW Ministry of Health

Funding body NSW Ministry of Health
Project Team Doctor Adjanie Patabendige
Scheme Early-Mid Career Fellowships
Role Lead
Funding Start 2018
Funding Finish 2021
GNo G1701366
Type Of Funding Other Public Sector - State
Category 2OPS
UON Y

20172 grants / $30,000

Understanding the pathophysiology of impaired brain fluid homeostasis using aquaporin modulators$20,000

Funding body: John Hunter Hospital Charitable Trust

Funding body John Hunter Hospital Charitable Trust
Project Team Doctor Adjanie Patabendige, Professor Neil Spratt
Scheme Research Grant
Role Lead
Funding Start 2017
Funding Finish 2017
GNo G1700474
Type Of Funding C3112 - Aust Not for profit
Category 3112
UON Y

The role of brain water channels in modulating cerebrospinal fluid (CSF) production$10,000

Funding body: NSW Ministry of Health

Funding body NSW Ministry of Health
Project Team Doctor Adjanie Patabendige, Professor Neil Spratt
Scheme Medical Research Support Program (MRSP)
Role Lead
Funding Start 2017
Funding Finish 2017
GNo G1701223
Type Of Funding C2220 - Aust StateTerritoryLocal - Other
Category 2220
UON Y

20131 grants / $700,000

Vector competence of British mosquitoes to flaviviruses$700,000

Funding body: Biotechnology and Biological Sciences Research Council (BBSRC)

Funding body Biotechnology and Biological Sciences Research Council (BBSRC)
Project Team

Matthew Baylis, Sareen Galbraith, Tom Solomon, Daniel Impoinvil, Adjanie Patabendige

Scheme Research Grant
Role Investigator
Funding Start 2013
Funding Finish 2017
GNo
Type Of Funding International - Competitive
Category 3IFA
UON N

20121 grants / $350,000

Optimisation of a flow-based human in vitro blood-brain barrier model$350,000

Funding body: The National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs)

Funding body The National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs)
Project Team

Adjanie Patabendige

Scheme David Sainsbury Fellowship
Role Lead
Funding Start 2012
Funding Finish 2016
GNo
Type Of Funding International - Competitive
Category 3IFA
UON N
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Research Supervision

Number of supervisions

Completed5
Current3

Current Supervision

Commenced Level of Study Research Title Program Supervisor Type
2018 PhD Intracranial Pressure Elevation and Cerebrospinal Fluid Change After Ischaemic Stroke PhD (Human Physiology), Faculty of Health and Medicine, The University of Newcastle Co-Supervisor
2015 PhD The Role of Water Transporting Channels in the Central Nervous System in Intracranial Pressure Elevation Following Stroke PhD (Human Physiology), Faculty of Health and Medicine, The University of Newcastle Co-Supervisor
2013 PhD Examining the pathogenesis of Enterovirus 71 infection using human cellular models Microbiology, University of Liverpool Co-Supervisor

Past Supervision

Year Level of Study Research Title Program Supervisor Type
2016 PhD Blood-brain barrier disruption in bacterial meningitis Biochemistry & Cell Biology, University of Liverpool Principal Supervisor
2014 Masters Comparison of Natalizumab and Mitoxantrone on a cellular model of the blood-brain barrier Medical Science, University of Liverpool Principal Supervisor
2014 Masters The effect of Natalizumab on the blood-brain barrier in Neuromyelitis Optica Medical Science, University of Liverpool Principal Supervisor
2013 Masters Therapeutic potential of selective COX inhibitors as neuroinflammatory modulators Biochemistry & Cell Biology, University of Liverpool Principal Supervisor
2013 Masters Investigation of the role of cyclooxygenase (COX) on the blood-brain barrier in viral encephalitis Biochemistry & Cell Biology, University of Liverpool Principal Supervisor
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Research Opportunities

The role of aquaporins in impaired brain fluid homeostasis

This project aims to explore the role of brain water channels in impaired brain fluid homeostasis in ischaemic stroke using in vitro models and pharmacological agents, in collaboration with a UK biotechnology company.

Honours

School of Biomedical Sciences and Pharmacy

28/01/2019 - 29/11/2019

Contact

Doctor Adjanie Patabendige
University of Newcastle
School of Biomedical Sciences and Pharmacy
adjanie.patabendige@newcastle.edu.au

PhD scholarship - Intracranial pressure elevation and cerebrospinal fluid change after ischaemic stroke

The studies will fall within a program of work within our laboratory, in which we aim to elucidate the mechanisms causing transient intracranial pressure elevation following ischaemic stroke and how this rise in pressure alters blood flow to vulnerable brain regions and secondary infarct expansion. We also aim to evaluate novel interventions that may halt these processes in preclinical stroke models such as short-duration therapeutic hypothermia. Full HDR scholarship available for both domestic and international students. Must start by October 2018.

PHD

Faculty of Health and Medicine

1/08/2018 - 31/07/2021

Contact

Doctor Adjanie Patabendige
University of Newcastle
School of Biomedical Sciences and Pharmacy
adjanie.patabendige@newcastle.edu.au

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Research Collaborations

The map is a representation of a researchers co-authorship with collaborators across the globe. The map displays the number of publications against a country, where there is at least one co-author based in that country. Data is sourced from the University of Newcastle research publication management system (NURO) and may not fully represent the authors complete body of work.

Country Count of Publications
United Kingdom 12
United States 2
Australia 1
Canada 1
Estonia 1
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News

Funding success to aid early interventions for cancer and stroke

July 16, 2018

Two exceptional Early to Mid-Career Researchers have secured more than $1.16 million to explore early intervention methods for two significant health challenges

Newcastle innovators awarded grants to go global

June 22, 2018

Two leading academics from the University of Newcastle are among the 38 beneficiaries in the latest round of the Australian Government’s Priming Grants, aimed at building international relationships to commercialise ground-breaking research.

Dr Adjanie Patabendige

Position

NSW Health EMC Fellow
School of Biomedical Sciences and Pharmacy
Faculty of Health and Medicine

Contact Details

Email adjanie.patabendige@newcastle.edu.au
Phone (02) 4921 7856
Link Twitter

Office

Room MSB503
Building Medical Sciences Building
Location Callaghan
University Drive
Callaghan, NSW 2308
Australia
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