Dr Jonathan Paul
School of Medicine and Public Health (Reproductive Medicine)
- Phone:(02) 4042 0348
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.
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.
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. 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 applied his dedicated his research to elucidating the mechanisms behind human parturition and the onset of labour.
Dr. Paul’s 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
- PhD (Biological Science), University of Newcastle
- Bachelor of Biotechnology, University of Newcastle
- Bachelor of Biotechnology (Honours), University of Newcastle
- preterm birth
- reproductive medicine
- smooth muscle contraction
- targeted drug delivery
Fields of Research
|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|
|Dates||Title||Organisation / Department|
|1/01/2015 - 31/12/2015||Associate Lecturer||University of Newcastle|
School of Medicine and Public Health
|17/07/2006 - 15/12/2006||Casual Academic||University of Newcastle|
School of Environmental and Life Sciences
For publications that are currently unpublished or in-press, details are shown in italics.
Chapter (2 outputs)
|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]|
|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]|
Journal article (9 outputs)
|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, (2015)|
|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 Ãinhibitory 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 Ã-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 Ã-inhibitory protein expression, which likely contributes to the weak contractions and poor labour outcomes observed in many obese women necessitating caesarean delivery. Â© 2014 Macmillan Publishers Limited.
|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]|
|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]|
|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]|
|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]|
|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]|
|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]|
|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]|
|Show 6 more journal articles|
Conference (16 outputs)
|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]|
|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]|
|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]|
|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]|
|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]|
|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]|
|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]|
|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]|
|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]|
|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]|
|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]|
|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]|
|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]|
|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]|
|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]|
|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]|
|Show 13 more conferences|
Grants and Funding
|Number of grants||5|
Click on a grant title below to expand the full details for that specific grant.
20151 grants / $2,000
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|
|Type Of Funding||Internal|
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
20121 grants / $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|
|Type Of Funding||Other Public Sector - State|
20091 grants / $15,208
Funding body: John Hunter Hospital Charitable Trust Fund
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|
|Type Of Funding||Other Public Sector - Commonwealth|
|Commenced||Research Title / Program / Supervisor Type|
|2014||Understanding Human Labour: Emergence of Synchrony in the Myometrium|
Medical Studies, Faculty of Health and Medicine
|2011||Elucidating the Role of Myosin Phosphatase in the Contractility of Myometrial Smooth Muscle|
Medical Studies, Faculty of Health and Medicine
Dr Jonathan Paul
Mothers and Babies Research Center
School of Medicine and Public Health
Faculty of Health and Medicine
|Phone||(02) 4042 0348|
|Fax||(02) 4042 0045|
|Room||Level 3, East|
|Building||HMRI, John Hunter Hospital Campus|
Callaghan, NSW 2308