Dr Jonathan Paul

Dr Jonathan Paul

Associate Lecturer

School of Medicine and Public Health (Reproductive Medicine)

Targeting better outcomes for mothers and babies

An emerging leader in the field of reproductive medicine, Dr Jonathan Paul has been internationally recognised for his work on targeting therapeutic nanoparticles to the muscle cells of the uterus.

Dr Jonathan Paul 

THE DELIVERY SUITE

Dr Jonathan Paul is a member of a team of multidisciplinary researchers at the University of Newcastle's Mothers and Babies Research Centre, who work to determine the cause, and most effective therapeutic approach, to maternal, foetal and neonatal health problems in humans.

The post-doctoral scientist is applying his expertise to a new mode of medication delivery to the uterus, which has the potential to radically decrease risks related to childbirth.  

Jonathan's revolutionary drug delivery vector has the capacity to increase the effectiveness of targeted therapeutics, potentially resulting in: halting pre-term labour, inducing or accelerating non-productive labour, or stemming postpartum bleeding.

The unique system has garnered Jonathan much attention due to the potential to save countless lives before, during and after childbirth. In early 2015, Jonathan was awarded the Presidential New Investigators Award by the Society for Reproductive Investigation at their 62nd Annual Meeting in San Francisco.

THE CELL EXPRESS

Jonathan completed his PhD as a member of the Reproductive Science Group at the University of Newcastle, focusing on proteins expressed on the surface of ova and their relevance to sperm ova interaction.

Jonathan then joined the Mothers and Babies team to undertake analysis of the protein changes that occur during the transition of uterine cells from non-contractile to contractile. His skill in the lab has secured his involvement in many projects within the Centre.

Working in collaboration with the Director, Professor Roger Smith, and Dr Susan Hau, Jonathan has been an integral member of the team that have created, and are currently testing, a system of targeted medication delivery.

The uterus is one of the organs in the body that is made of smooth muscle. Currently, medications administered to stimulate or relax the uterus have been designed for use in other areas of the body.  As such, they can have off-target affects, limiting both the range of drugs that can be administered safely, and the effectiveness of those chosen drugs.

Jonathan's new system targets a particular protein, ensuring the medication is directed specifically to the uterus.

A SPOONFUL OF NANOPARTICLES

Liposomes (tiny bubbles made from the same material as a cell membrane) deliver the medication by seeking out specific proteins. Jonathan explains:

"Our cells are surrounded by a membrane. We take a small section of artificial membrane, make a tiny sphere, encapsulate the drug inside that sphere, then we target that sphere to the uterus."

"What we have done is to look for a particular protein that is expressed in high abundance only on uterine cells.  We've then targeted the liposomes to that protein."

This targeted delivery system has the following benefits: it increases the effectiveness of existing medication; and offers the possibility of utilising drugs previously considered unsafe due to affects on other organs and tissues.

RIGHT ON TARGET

Complications related to childbirth create considerable short and long term strains on mother and baby, as well as the health care system. There are several stages of pregnancy and labour that present a danger, especially in less developed countries. 

Pre-term birth is the major cause of neo-natal morbidity and mortality, and is responsible for more than half the cases of cerebral palsy. Pre-term infants who survive can be left with on-going complications such as asthma, eye or hearing problems, and increased long-term risk of developing several conditions such as diabetes and heart disease.

If a pregnancy approaches 42 weeks a caesarian section will be performed to counter the increased risk of intra-uterine death. This resource intensive procedure may discourage the mother from giving birth naturally in future deliveries. In less developed countries, a c-section may not be an option.

If the uterus fails to contract following delivery, post-partum hemorrhage may result. In less developed countries, where there is limited or no access to medicines such as oxytocin (which promotes contractions and the restriction of blood vessels), excessive blood loss can result in death.  

Using the targeted drug delivery system, liposomes could be filled with medication aimed at maximising uterine contraction, thus restricting the body's ability to lose blood. When a pregnancy has continued past 42 weeks, the liposomes could be loaded with medication aimed at stimulating or increasing contractility. If pre-term labour has begun, the liposomes would be loaded with medication to halt contractions.

PROGRESSING TO TERM

Jonathan has achieved great success trialing the delivery system on uterine tissue harvested during myometrium biopsies. Further research using a mouse model is underway.

A major cause of pre-term labour in women is inflammation arising from bacterial infection. Accordingly, infection is being simulated to test how effectively the targeted delivery system can work to halt contractions when pre-term labour occurs due to bacterial infection.

Progesterone withdrawal is another leading cause of pre-term labour, as it is essential to the maintenance of a pregnancy. Further research will be undertaken through a mouse model, to measure the efficacy of the targeted delivery system in the event of withdrawal of progesterone.

"The therapeutics we are looking at using target the raw mechanism of the contraction," says Jonathan.

"Regardless of what signaling events are occurring upstream, if we can disable that pathway and eliminate the ability of the cell to undergo the fundamentals of contractility, we should be able to block pre-term labour."

Assuming the success of the mouse model trials, the next step would be to test the efficacy of the system using a primate model. Jonathan hopes to eventually work in collaboration with the University of Washington's Infant Primate Research Laboratory within their Centre on Human Development and Disability.

PRO-TEAM PROTEIN

It is already clear that the drug delivery vector could be adapted to target cells in other areas of the body.

"You could target any number of tissue provided it has a specific marker. In this case we have used it to target the uterus but it certainly has a much bigger scope than that," Jonathan explains.

"If you have a cancer, for instance, that expresses a particular protein in high abundance relative to any other tissues or organs, then you could target those liposomes to the cancer cells."

Another area of research that is currently moving forward using the targeted delivery system is a project to fight ovarian cancer.

"I'm working with another post-doc, Dr Jorge Tolosa, with input from Roger Smith on this project," says Jonathan.

Completed trials suggest that the drug delivery vector is an acutely superior system when it comes to concentrating medication in the goal area.

Whether the targeted liposomes are stopping pre-term labour or attacking uterine cancer cells, this new system has the potential to save countless lives,  and revolutionise the way therapeutics are delivered.

Dr Jonathan Paul

Targeting better outcomes for mothers and babies

An emerging leader in the field of reproductive medicine, Dr Jonathan Paul has been internationally recognised for his work on targeting therapeutic nanoparti

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Career Summary

Biography

Dr. Paul completed his PhD within the Reproductive Sciences Group, under the leadership of Professor Eileen McLaughlin and Laureate Professor John Aitken. Dr. Paul then joined the Mothers and Babies Research Centre, where he has dedicated his research to elucidating the mechanisms behind human parturition and the onset of labour.

 Dr. Paul has a background in proteomics, and more recently has specialised in phospho-proteomics and how these techniques can be applied to elucidating changes associated with the onset of labour.

 “My research focuses on understanding the physiological changes that occur late in human pregnancy. I am primarily interested in elucidating the changes in uterine smooth muscle cells that are responsible for transforming a quiescent, non-contractile uterus, capable of expanding to accommodate a growing fetus, into an actively contracting muscular organ that is engaged in powerful synchronised contractions in order to deliver the fetus.

Recently, Dr. Paul’s research has focused on the development of a targeted drug delivery system for the uterus. Dr. Paul is part of a research team that has developed ‘targeted liposomes’, a type of organic nanoparticle capable of carrying a drug payload, as a means targeting therapeutic interventions specifically to the uterus.   

Dr. Paul’s research into the awakening of uterine smooth muscle cells and targeted drug delivery to these cells is ongoing, and has already served as the platform for multiple patents.


Qualifications

  • PhD (Biological Science), University of Newcastle
  • Bachelor of Biotechnology, University of Newcastle
  • Bachelor of Biotechnology (Honours), University of Newcastle

Keywords

  • labour
  • myometrium
  • nanomedicine
  • pregnancy
  • preterm birth
  • proteomics
  • reproductive medicine
  • smooth muscle contraction
  • targeted drug delivery

Fields of Research

Code Description Percentage
110199 Medical Biochemistry and Metabolomics not elsewhere classified 20
111499 Paediatrics and Reproductive Medicine not elsewhere classified 60
060109 Proteomics and Intermolecular Interactions (excl. Medical Proteomics) 20

Professional Experience

UON Appointment

Title Organisation / Department
Associate Lecturer University of Newcastle
School of Medicine and Public Health
Australia

Awards

Award

Year Award
2015 The Presidential New Investigator Award
Society of Reproductive Investigation

Prestigious works

Year Commenced Year Finished Prestigious Work Role
2015 2015 Video Publication: The Heart is Like an Orchestra, the Uterus is Like a Soccer Crowd Online Designer
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Publications

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


Chapter (2 outputs)

Year Citation Altmetrics Link
2013 Smith R, Paul J, Chan C, Keelan J, 'The role of the primate placenta in term and preterm parturition', The Placenta: Development, Function and Diseases, Nova Science, Hauppaugue, NY 335-346 (2013) [B1]
Co-authors Roger Smith
2012 Schjenken JE, Tolosa Gonzalez JM, Paul JW, Clifton VL, Smith R, 'Mechanisms of maternal immune tolerance during pregnancy', Recent Advances in Research on the Human Placenta, InTech, Rijeka, Croatia 211-242 (2012) [B1]
Co-authors Roger Smith

Journal article (9 outputs)

Year Citation Altmetrics Link
2015 Smith R, Imtiaz M, Banney D, Paul JW, Young RC, 'Why the heart is like an orchestra and the uterus is like a soccer crowd.', Am J Obstet Gynecol, 213 181-185 (2015)
DOI 10.1016/j.ajog.2015.06.040
Co-authors Roger Smith
2014 Parkington HC, Stevenson J, Tonta MA, Paul J, Butler T, Maiti K, et al., 'Diminished hERG K+ channel activity facilitates strong human labour contractions but is dysregulated in obese women', Nature Communications, 5 (2014) [C1]

Human ether-a-go-go-related gene (hERG) potassium channels determine cardiac action potential and contraction duration. Human uterine contractions are underpinned by an action pot... [more]

Human ether-a-go-go-related gene (hERG) potassium channels determine cardiac action potential and contraction duration. Human uterine contractions are underpinned by an action potential that also possesses an initial spike followed by prolonged depolarization. Here we show that hERG channel proteins (a-conducting and ßinhibitory subunits) and hERG currents exist in isolated patch-clamped human myometrial cells. We show that hERG channel activity suppresses contraction amplitude and duration before labour, thereby facilitating quiescence. During established labour, expression of ß-inhibitory protein is markedly enhanced, resulting in reduced hERG activity that is associated with an increased duration of uterine action potentials and contractions. Thus, changes in hERG channel activity contribute to electrophysiological mechanisms that produce contractions during labour. We also demonstrate that this system fails in women with elevated BMI, who have enhanced hERG activity as a result of low ß-inhibitory protein expression, which likely contributes to the weak contractions and poor labour outcomes observed in many obese women necessitating caesarean delivery. © 2014 Macmillan Publishers Limited.

DOI 10.1038/ncomms5108
Citations Scopus - 2Web of Science - 1
Co-authors Roger Smith
2013 Butler T, Paul J, Europe-Finner N, Smith R, Chan E-C, 'Role of serine-threonine phosphoprotein phosphatases in smooth muscle contractility', AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 304 C485-C504 (2013) [C1]
DOI 10.1152/ajpcell.00161.2012
Citations Scopus - 7Web of Science - 6
Co-authors Roger Smith
2012 Smith R, Paul JW, Maiti K, Tolosa Gonzalez JM, Madsen GM, 'Recent advances in understanding the endocrinology of human birth', Trends in Endocrinology & Metabolism, 23 516-523 (2012) [C1]
Citations Scopus - 6Web of Science - 5
Co-authors Gemma Madsen, Roger Smith
2012 Hure AJ, Collins CE, Giles WB, Paul JW, Smith R, 'Greater maternal weight gain during pregnancy predicts a large but lean fetal phenotype: A prospective cohort study', Maternal and Child Health Journal, 16 1374-1384 (2012) [C1]
DOI 10.1007/s10995-011-0904-8
Citations Scopus - 6Web of Science - 6
Co-authors Roger Smith, Alexis Hure, Clare Collins
2012 Welsh TN, Paul JW, Palliser HK, Tabatabaeehatambakhsh SH, Hirst JJ, Mesiano S, Zakar T, '15-hydroxyprostaglandin dehydrogenase expression and localization in guinea pig gestational tissues during late pregnancy and parturition', Reproductive Sciences, 19 1099-1109 (2012) [C1]
DOI 10.1177/1933719112442247
Citations Scopus - 2Web of Science - 2
Co-authors Jon Hirst, Hannah Palliser
2011 Paul JW, Maiti K, Read MA, Hure AJ, Smith JI, Chan EC, Smith R, 'Phasic phosphorylation of caldesmon and ERK 1/2 during contractions in human myometrium', PLoS ONE, 6 1-7 (2011) [C1]
DOI 10.1371/journal.pone.0021542
Citations Scopus - 8Web of Science - 7
Co-authors Alexis Hure, Roger Smith
2011 Maiti K, Paul JW, Read MA, Chan EC, Riley SC, Nahar P, Smith R, 'G-1-activated membrane estrogen receptors mediate increased contractility of the human myometrium', Endocrinology, 152 2448-2455 (2011) [C1]
DOI 10.1210/en.2010-0979
Citations Scopus - 16Web of Science - 14
Co-authors Roger Smith
2005 Nixon B, Paul JW, Spiller CM, Attwell-Heap AG, Ashman LK, Aitken RJ, 'Evidence for the involvement of PECAM-1 in a receptor mediated signal-transduction pathway regulating capacitation-associated tyrosine phosphorylation in human spermatozoa', Journal of Cell Science, 118 4865-4877 (2005) [C1]
DOI 10.1242/jcs.02604
Citations Scopus - 13Web of Science - 13
Co-authors Brett Nixon, John Aitken, Leonie Ashman
Show 6 more journal articles

Conference (16 outputs)

Year Citation Altmetrics Link
2012 Parkington HC, Paul JW, Tonta MA, Chan EC, Sheehan PJ, Brennecke SP, et al., 'Human labour is associated with decreased myometrial ether-a-go-go related gene (hERG) potassium channels that modulate contractility', Proceedings of the 39th Annual Meeting of the Fetal and Neonatal Physiological Society, Zeist, The Netherlands (2012) [E3]
Co-authors Roger Smith
2012 Welsh TN, Paul JW, Palliser HK, Hirst JJ, Mesiano S, Zakar T, 'PGDH expression decreases at term before labor onset in guinea pig fetal membranes', Reproductive Sciences, San Diego, CA (2012) [E3]
Co-authors Hannah Palliser, Jon Hirst
2011 Hure AJ, Collins CE, Giles WB, Paul JW, Smith R, 'A large but lean fetal phenotype is associated with greater maternal weight gain during pregnancy', Obesity Research & Clinical Practice, Adelaide (2011) [E3]
Co-authors Alexis Hure, Roger Smith, Clare Collins
2011 Paul JW, Maiti K, Read MA, Hure AJ, Smith JI, Chan EC, Smith R, 'Studying laboring myometrium misses phosphorylation changes associated with contraction', Reproductive Sciences, Miami Beach (2011) [E3]
Co-authors Roger Smith, Alexis Hure
2010 Maiti K, Paul JW, Read MA, Chan EC, Smith R, 'Human labor Is associated with internalization and oligomerization of the membrane estrogen receptor, GPR30', Reproductive Sciences, Orlando, Florida (2010) [E3]
Co-authors Roger Smith
2010 Maiti K, Paul JW, Chan EC, Smith R, 'GPR30, the novel membrane estrogen receptor, stimulates contractility of myometrium by increasing expression of h-caldesmon', The Endocrine Society of Australia Annual Scientific Meeting Meeting Proceedings and Abstract Book, Sydney (2010) [E3]
Co-authors Roger Smith
2010 Paul JW, Maiti K, Read MA, Smith R, 'Caldesmon phosphorylation and phasic regulation of ERK 1/2 during contractions in human myometrium', The Endocrine Society of Australia Annual Scientific Meeting Proceedings and Abstract Book, Sydney (2010) [E3]
Co-authors Roger Smith
2009 Maiti K, Paul JW, Read MA, Chan EC, Smith R, 'Demonstration that activation of the cell surface estrogen receptor GPR30 causes phosphorylation of HSP27 and MAPK p42/44 in term human myometrial tissue and explants', Reproductive Sciences, Glasgow, Scotland (2009) [E3]
Co-authors Roger Smith
2009 Paul JW, Read MA, Smith R, 'Phosphorylation events associated with myometrial awakening and the development of contractile force in humans', Reproductive Sciences, Glasgow, Scotland (2009) [E3]
Co-authors Roger Smith
2008 Maiti K, Paul JW, Read MA, Chan EC, Smith R, 'Presence of the novel membrane estrogen receptor G-Protein coupled receptor 30 (GPR30) a membrane estrogen receptor in human pregnant myometrium and its biochemical characterization', 51st Annual Scientific Meeting of the Endocrine Society of Australia and Society of Reproductive Biology: Meeting Proceedings and Abstract Book, Melbourne, VIC (2008) [E3]
Co-authors Roger Smith
2008 Paul JW, Read MA, Chan EC, Smith R, 'Phospho-proteomic determination of contraction associated proteins in the human uterus', 51st Annual Scientific Meeting of the Endocrine Society of Australia and Society of Reproductive Biology: Meeting Proceedings and Abstract Book, Melbourne, VIC (2008) [E3]
Co-authors Roger Smith
2006 Paul JW, Aitken RJ, McLaughlin EA, 'Oolemmal Proteomics: Characterisation of Glycophosphatidylinositol Anchored Proteins Involved in Murine Fertilisation', Book of Abstracts, Lorne, Victoria, Australia (2006) [E3]
Co-authors John Aitken, Eileen Mclaughlin
2006 Nixon B, Paul JW, Spiller CM, Attwell-Heap AG, Aitken RJ, 'Evidence for the Involvement of Pecam-1 in a Reception Mediated Signal-Transduction Pathway regulating Capacitation-Associated Tyrosine Phosphorylation in Human Spermatozoa', Book of Abstracts, Lorne, Victoria, Australia (2006) [E3]
Co-authors John Aitken, Brett Nixon
2004 Paul JW, McLaughlin EA, Aitken RJ, 'Oolemmal Proteomics: Identification of the Oocyte Cell Surface Protein Complexes Involved in Sperm-egg Interaction', Reproduction, Fertility and Development, Sydney (2004) [E3]
Co-authors Eileen Mclaughlin, John Aitken
2003 Nixon B, Paul JW, Aitken RJ, 'Wheat germ agglutinin induced tyrosine phosphorylation of human spermatozoa', 28th Annual Lorne Conference on Protein Structure & Function, Lorne, Victoria (2003) [E3]
Co-authors Brett Nixon, John Aitken
2003 Nixon B, Attwell-Heap AG, Paul JW, Aitken RJ, 'Wheat Germ Agglutinin Induced Tyrosine Phosphorylation of Human Spermatozoa', Reproduction, Fertility and Development, Melbourne (2003) [E3]
Co-authors Brett Nixon, John Aitken
Show 13 more conferences
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Grants and Funding

Summary

Number of grants 9
Total funding $225,509

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


20153 grants / $93,222

A Safer Way of Treating Premature Labor and Post- Partum Haemorrhage$66,000

Funding body: Global Alliance to Prevent Prematurity and Stillbirth (GAPPS)

Funding body Global Alliance to Prevent Prematurity and Stillbirth (GAPPS)
Project Team
Scheme GAPPS
Role Investigator
Funding Start 2015
Funding Finish 2016
GNo
Type Of Funding International - Competitive
Category 3IFA
UON N

Developing a system for targeting drugs to ovarian cancer$25,222

Funding body: John Hunter Hospital Charitable Trust Fund

Funding body John Hunter Hospital Charitable Trust Fund
Project Team
Scheme Research Grant
Role Lead
Funding Start 2015
Funding Finish 2015
GNo
Type Of Funding Other Public Sector - State
Category 2OPS
UON N

Society of Reproductive Investigation (SRI) 62nd Annual Scientific Meeting, San Francisco USA, 25-28 March 2015$2,000

Funding body: University of Newcastle - Faculty of Health and Medicine

Funding body University of Newcastle - Faculty of Health and Medicine
Project Team Doctor Jonathan Paul
Scheme Travel Grant
Role Lead
Funding Start 2015
Funding Finish 2016
GNo G1500525
Type Of Funding Internal
Category INTE
UON Y

20141 grants / $25,000

Achieving Targeted Delivery of Drugs to Uterine Muscle in Women for the Prevention of Preterm Labour$25,000

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Doctor Jonathan Paul, Doctor Susan Hua, Professor Roger Smith
Scheme Project Grant
Role Lead
Funding Start 2014
Funding Finish 2014
GNo G1401504
Type Of Funding Grant - Aust Non Government
Category 3AFG
UON Y

20121 grants / $34,454

Targeting the ether-a-go-go potassium channel as a treatment for post-partum heamorrhage$34,454

Funding body: John Hunter Hospital Charitable Trust Fund

Funding body John Hunter Hospital Charitable Trust Fund
Project Team Dr Andrew Carlin, Doctor Jonathan Paul
Scheme Research Grant
Role Lead
Funding Start 2012
Funding Finish 2012
GNo G1200956
Type Of Funding Other Public Sector - State
Category 2OPS
UON Y

20111 grants / $25,000

Role of the potassium channel hERG in regulating the onset of labor in humans$25,000

Funding body: John Hunter Hospital Charitable Trust Fund

Funding body John Hunter Hospital Charitable Trust Fund
Project Team
Scheme Research Grant
Role Lead
Funding Start 2011
Funding Finish 2011
GNo
Type Of Funding Other Public Sector - State
Category 2OPS
UON N

20101 grants / $23,025

Identification of protein modifications associated with myometrial activation during the onset of labour$23,025

Funding body: John Hunter Hospital Charitable Trust Fund

Funding body John Hunter Hospital Charitable Trust Fund
Project Team
Scheme Research Grant
Role Lead
Funding Start 2010
Funding Finish 2010
GNo
Type Of Funding Other Public Sector - State
Category 2OPS
UON N

20091 grants / $15,208

Apoptosis in pregnant human myometrium and its role in labour$15,208

Funding body: John Hunter Hospital Charitable Trust Fund

Funding body John Hunter Hospital Charitable Trust Fund
Project Team Doctor Kaushik Maiti, Doctor Jonathan Paul, Doctor Pravin Nahar
Scheme Research Grant
Role Investigator
Funding Start 2009
Funding Finish 2009
GNo G0189933
Type Of Funding Other Public Sector - State
Category 2OPS
UON Y

20081 grants / $9,600

LED fluorescence illuminators and filter set (525nm + 575DF20) for LAS3000 image analysis system$9,600

Funding body: NHMRC (National Health & Medical Research Council)

Funding body NHMRC (National Health & Medical Research Council)
Project Team Professor Roger Smith, Professor Ian Symonds, Conjoint Associate Professor Andrew Bisits, Conjoint Professor Tam Zakar, Doctor John Fitter, Doctor Cheng Chan, Conjoint Associate Professor Rick Nicholson, Doctor Giavanna Angeli, Doctor Kaushik Maiti, Doctor Jonathan Paul, Professor Jon Hirst, Doctor Hannah Palliser, Professor Eugenie Lumbers
Scheme Equipment Grant
Role Investigator
Funding Start 2008
Funding Finish 2008
GNo G0188543
Type Of Funding Other Public Sector - Commonwealth
Category 2OPC
UON Y
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Research Supervision

Current Supervision

Commenced Research Title / Program / Supervisor Type
2014 Understanding Human Labour: Emergence of Synchrony in the Myometrium
Medical Studies, Faculty of Health and Medicine
Co-Supervisor
2011 Elucidating the Role of Myosin Phosphatase in the Contractility of Myometrial Smooth Muscle
Medical Studies, Faculty of Health and Medicine
Co-Supervisor
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Dr Jonathan Paul

Position

Associate Lecturer
Mothers and Babies Research Center
School of Medicine and Public Health
Faculty of Health and Medicine

Focus area

Reproductive Medicine

Contact Details

Email jonathan.paul@newcastle.edu.au
Phone (02) 4042 0348
Fax (02) 4042 0045

Office

Room Level 3, East
Building HMRI, John Hunter Hospital Campus
Location Callaghan
University Drive
Callaghan, NSW 2308
Australia
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