Dr Suzanne Miller - Researcher Profile

Suzanne Miller

Address

Monash Institute of Medical Research, The Ritchie Center
27-31 Wright Street, Clayton

Biography

Protecting babies from dangerous free radicals

Dr Suzanne Miller leads a group of researchers at the Monash Institute of Medical Research’s Ritchie Centre who are looking at how the foetus develops, particularly the brain, and how to protect it. She very concerned about free radicals, not the activist kind, but the kind overproduced in the womb when poor oxygen supply or infection can lead to brain and other damage. But her team has identified a way to deal with them.

Dr Suzanne Miller is a foetal physiologist. She investigates how foetuses grow and what happens when things go wrong. That could be asphyxia, an acute lack of oxygen just before or at birth, chronic hypoxia, a moderate but ongoing lack of oxygen during pregnancy, or infection, which causes inflammation of the membranes that surrounds a foetus.

Such events during pregnancy or at birth can lead to poorly developed organs, including the lungs, heart and brain. Suzanne is most concerned with the brain because its abnormal development can lead to learning disabilities or cerebral palsy – the most common physical disability in children, which leaves them with little, if any, movement in their arm or legs.

These possibilities keep everyone at the Ritchie Centre – research scientists like Suzanne and the clinicians with whom she works – focused on finding new ways to minimise and repair damage to unborn and newborn babies.

Her teams’ latest treatment for asphyxia and chronic hypoxia, which they’ve tested successfully on animals, uses an antioxidant known as melatonin to protect foetuses and newborn babies against oxygen free radicals.

“A placenta that’s not functioning properly during pregnancy can result in the production of oxygen free radicals, which can also be produced in healthy pregnancies at the time of a difficult birth,” she says. “It’s these free radicals that are thought to do most much of the damage to vulnerable brains.”

Melatonin is a natural hormone that sets our circadian rhythms, but Suzanne and her team found that its powerful antioxidant properties reduced oxygen free radicals, especially the highly destructive hydroxyl radical.

The potential treatment offers hope to the eight per cent of pregnant mothers with malfunctioning placentas that can deprive their babies of oxygen and cause intrauterine growth restriction or IUGR.

 

 

“By giving melatonin to the mum, we’re not completely ameliorating the production of oxygen free radicals in the placenta, but we’re certainly holding it at a more appropriate level, which is below the level normally found in IUGR pregnancies,” Suzanne says.

Babies suffering from IUGR, which ultrasound can detect at about 20 weeks, risk being stillborn or suffering heart and lung damage, not just brain injury.

Another of her team’s potential treatments for high-risk pregnancies uses an anti-inflammatory compound to treat chorioamnionitis, an infection of the foetal membranes that often leads to preterm births and high rates of cerebral palsy.

After discovering that melatonin didn’t help here, Suzanne and her team turned to Sulfasalazine, a broad-spectrum anti-inflammatory drug, used to treat pregnant women with painful arthritis. Having found that it also reduces inflamed foetal membranes, they plan to design a more targeted drug.

While treatments to prevent damage are at the forefront of their work, Suzanne and her Ritchie Centre colleagues know that preventing brain injury is not always possible. They’re now trialling the use of stem cells, taken from placentas after birth, to repair damage to babies in the womb or at birth.

Their research is at an early stage, but the results from animal testing are promising. When they injected human amnion epithelial cells into foetal lambs, they weren’t sure they would gain access to the brain, which Suzanne says “is very fussy about what can and can’t pass through its strictly controlled blood-brain barrier”.

“But we’ve found them in quite large numbers within the brain, which suggests that they’re homing to the sites of injury. Whether or not they’re repairing injury at this stage, we’re not sure, but, fingers crossed. They’re certainly getting there.”

Suzanne credits the Ritchie Centre’s success at finding novel treatments for at-risk mothers and babies to the constant collaboration and interaction between the scientists and practising doctors who work there.

“When we’re doing experiments, we have all hands on deck. We have people saying, ‘We should try this,’ or ‘What about doing this kind of targeted therapy.’ This collaborative approach to research really works.”

 

Qualifications

DOCTOR OF PHILOSOPHY
Institution: Monash University
Year awarded: 1999
BACHELOR OF SCIENCE WITH HONOURS
Institution: Monash University
Year awarded: 1993

Publications

Journal Articles

Miller, S.L., Sutherland, A.E., Supramaniam, V.G., Walker, D.W., Jenkin, G., Wallace, E.M., 2012, Antenatal glucocorticoids reduce growth in appropriately grown and growth-restricted ovine fetuses in a sex-specific manner, Reproduction, Fertility and Development [P], vol 24, issue 5, C S I R O Publishing, Australia, pp. 753-758.

Miller, S.L., Wallace, E.M., Walker, D.W., 2012, Antioxidant therapies: A potential role in perinatal medicine, Neuroendocrinology [P], vol 96, issue 1, S Karger AG, Switzerland, pp. 13-23.

Tare, M., Miller, S.L., Wallace, E.M., Sutherland, A.E., Yawno, T., Coleman, H.A., Jenkin, G., Parkington, H.C., 2012, Glucocorticoid treatment does not alter early cardiac adaptations to growth restriction in preterm sheep fetuses, Bjog-An International Journal Of Obstetrics And Gynaecology [P], vol 119, issue 8, Wiley-Blackwell Publishing Ltd, UK, pp. 906-914.

Hodges, R., Jenkin, G., Hooper, S., Allison, B., Lim, R., Dickinson, H., Miller, S., Vosdoganes, P., Wallace, E., 2012, Human amnion epithelial cells reduce ventilation-induced preterm lung injury in fetal sheep , American Journal Of Obstetrics And Gynecology [P], vol 206, issue 5 (Art. No.: 448), Mosby Inc., United States, pp. 8-15.

Polglase, G., Miller, S.L., Barton, S., Baburamani, A.A., Wong, F.Y., Aridas, J., Gill, A.W., Moss, T.J.M., Tolcos, M., Kluckow, M., Hooper, S.B., 2012, Initiation of resuscitation with high tidal volumes causes cerebral hemodynamic disturbance, brain inflammation and injury in preterm lambs, PLoS ONE [P], vol 7, issue 6 (Art. No: e39535), Public Library of Science, United States, pp. 1-8.

Sutherland, A., Crossley, K., Allison, B., Jenkin, G., Wallace, E., Miller, S., 2012, The effects of intrauterine growth restriction and antenatal glucocorticoids on ovine fetal lung development, Pediatric Research [P], vol 71, issue 6, Nature Publishing Group, United States, pp. 689-696.

Bertucci, M.C., Loose, J.M., Wallace, E.M., Jenkin, G., Miller, S.L., 2011, Anti-inflammatory therapy in an ovine model of fetal hypoxia induced by single umbilical artery ligation, Reproduction, Fertility and Development [P], vol 23, issue 2, CSIRO Publishing, Australia, pp. 346-352.

Rodricks, C.L., Gibbs, M.E., Castillo-Melendez, M., Miller, S.L., 2010, The effect of hypoxia on the functional and structural development of the chick brain, International Journal of Developmental Neuroscienc..., vol 28, issue 4, Pergamon, UK, Canada, pp. 343-350.

Miller, S.L., Supramaniam, V.G., Jenkin, G., Walker, D.W., Wallace, E.M., 2009, Cardiovascular responses to maternal betamethasone administration in the intrauterine growth-restricted ovine fetus, American Journal Of Obstetrics And Gynecology [P], vol 201, issue 6, Mosby, Inc., USA, pp. 613.e1-613.e8.

Gibbs, M.E., Rodricks, C.L., Hutchinson, D.S., Summers, R.J., Miller, S.L., 2009, Importance of adrenergic receptors in prenatally induced cognitive impairment in the domestic chick, International Journal of Developmental Neuroscience, vol 27, Pergamon, UK, pp. 27-35.

Miller, S.L., Loose, J.M., Jenkin, G., Wallace, E.M., 2009, The effects of sildenafil citrate (Viagra) on uterine blood flow and well being in the intrauterine growth-restricted fetus, American Journal of Obstetrics and Gynecology, vol 200, issue 1, Mosby, Inc., USA, pp. 102.e1-102.e7.

Rodricks, C.L., Gibbs, M.E., Jenkin, G., Miller, S.L., 2008, The effect of hypoxia at different embryonic ages on impairment of memory ability in chicks, International Journal of Developmental Neuroscience, vol 26, Pergamon-Elsevier Science Ltd, Oxford England UK, pp. 113-118.

Miller, S.L., Chai, M., Loose, J.M., Castillo-Melendez, M., Walker, D.W., Jenkin, G., Wallace, E.M., 2007, The effects of maternal betamethasone administration on the intrauterine growth-restricted fetus, Endocrinology, vol 148, issue 3, The Endocrine Society, Chevy Chase USA, pp. 1288-1295.

Supramaniam, V.G., Jenkin, G., Loose, J.M., Wallace, E.M., Miller, S.L., 2006, Chronic fetal hypoxia increases activin A concentrations in the late-pregnant sheep, BJOG-An International Journal of Obstetrics and Gynaecology, vol 113, issue 1, Blackwell Publishing, Oxford England, pp. 102-109.

Rodricks, C.L., Miller, S.L., Jenkin, G., Gibbs, M.E., 2006, The role of corticosterone in prehatch-induced memory deficits in chicks, Brain Research, vol 1123, Elsevier Science BV, Amsterdam The Netherlands, pp. 34-41.

Miller, S.L., Yan, E.B., Castillo-Melendez, M.E., Jenkin, G., Walker, D.W., 2005, Melatonin provides neuroprotection in the late-gestation fetal sheep brain in response to umbilical cord occlusion, Developmental Neuroscience, vol 27, issue 2-4, S Karger AG, Switzerland, pp. 200-210.

Yan, E.B., Unthank, J.K., Castillo-Melendez, M.E., Miller, S.L., Langford, S.J., Walker, D.W., 2005, Novel method for in vivo hydroxyl radical measurement by microdialysis in fetal sheep brain in utero, Journal of Applied Physiology, vol 98, issue 6, American Physiological Society, USA, pp. 2304-2310.

Smith, R.P., Miller, S.L., Igosheva, N., Peebles, N., Glover, V.M., Jenkin, G., Hanson, M.A., Fisk, N.M., 2004, Cardiovascular and endocrine responses to cutaneous electrical stimulation after fentanyl in the ovine fetus, American Journal of Obstetrics and Gynecology, vol 3, issue 190, Mosby, Inc, USA, pp. 836-842.

Loose, J.M., Miller, S.L., Supramaniam, V.G., Ward, J.W.A., O'Connor, A.E., de Kretser, D.M., Wallace, E.M., Jenkin, G., 2004, Hypoxia induced activin secretion by the fetoplacental unit: differential responses related to gestation. IF 2.171, British Journal of Obstetrics and Gynaecology, vol 111, Blackwell Publishing, Oxford England, pp. 1346-1352.

Supramaniam, V.G., Jenkin, G., Wallace, E.M., O'Connor, A.E., de Kretser, D.M., Miller, S.L., 2004, The effect of graded hypoxia on activin A, PGE2 and cortisol levels in the late pregnant sheep, Reproduction Fertility and Development:15, 625 - 632, vol 16, CSIRO Publishing, Collingwood Vic Australia, pp. 625-632.

Rodricks, C.L., Rose, I.A., Camm, E.J., Jenkin, G., Miller, S.L., Gibbs, M.E., 2004, The effect of prenatal hypoxia and malnutrition on memory consolidation in the chick, Developmental Brain Research, vol 148, issue 1, Elsevier, Amsterdam The Netherlands, pp. 113-119.

Miller, S., Jenkin, G., Walker, D.M., 2000, Effects of hyperthermia on uterine blood flow and shunting through uterine arteriovenous anastomoses in the late-pregnant ewe, Reproduction Fertility and Development, vol 11 issue 45, CSIRO Publications, Melbourne Vic Australia, pp. 201-209.

Miller, S., Jenkin, G., Walker, D.M., 1999, The effects of nitric oxide synthase inhibition on the uterine vasculature of the late pregnant ewe, American Journal of Obstetrics and Gynaecology, vol 180, Mosby-Year Book Inc, St Louis MO USA, pp. 1138-1145.

Miller, S., Dickson, K.A., Jenkin, G., Walker, D.M., 1998, Physiological evidence for arterioivenous anastomoses in the unterine circulation of late pregnant ewes, Clinical and Experimental Pharmacology and Physiology, vol 25, Blackwell Science, Melbourne Vic Australia, pp. 92-98.

Miller, S., Wongprasartsuk, S., Young, I.R., Wlodek, M.E., McFarlane, J.R., de Kretser, D.M., Jenkin, G., 1997, Source of Inhibin in Ovine Fetal Plasma and Amniotic Fluid, Biology of Reproduction, vol 57, Society for the Study of Reproduction, Wisconsis USA, pp. 347-353.

Miller, S., Wongprasartsuk, S., Young, I.R., Wlodek, M.E., McFarlane, J.R., de Kretser, D.M., Jenkin, G., 1997, Source of inhibin in ovine fetal plasma and amniotic fluid during late gestation: Half-life of fetal inhibin, Biology of Reproduction, vol 57, Society for the Study of Reproduction, Madison Wisconsin USA, pp. 347-353.

Conference Proceedings

Miller, S., Jenkin, G., Walker, D.M., 1997, Physiological evidence for the presence of arteriovenous anastomoses in the uterine circulation of late pregnant sheep, Fetal and Neonatal Physiological Society, St Margherita Ligure Genoa Italy,15-18 June 1997, Fetal and Neonatal Physiological Society, Genoa Italy, p. 69.

Miller, S., Jenkin, G., Walker, D.M., 1997, Physiological evidence for the presence of arteriovenous anastomoses in the uterine circulation of late-pregnant ewes, Fetal & Neonatal Physiology Symposium/IUPS Congress Abstract Handbook, Cambridge UK, 25-29 June 1997, R & W Publications, Cambridge UK, p. 97.

Miller, S., Jenkin, G., Walker, D.M., 1997, The effects of nitric oxide inhibition of the uterine vasculature of the late-pregnant ewe, Fetal and Neonatal Physiological Society, Santa Margherito, Genoa, Italy, 15-18 June, Fetal and Neonatal Physiological Society, Italy, p. 9.

Postgraduate Research Supervisions

Current Supervision

Program of Study:
(DOCTORATE BY RESEARCH).
Thesis Title:
Neonatal neurodevelopment after antioxidant with melatonin during late-pregnancy in an ovine model of intrauterine growth restriction.
Supervisors:
Jenkin, G (Main), Miller, S (Associate), Wallace, E (Associate).
Program of Study:
(DOCTORATE BY RESEARCH).
Thesis Title:
Protecting the newborn brain following asphyxia at birth.
Supervisors:
Jenkin, G (Joint-co), Miller, S (Joint).
Program of Study:
(DOCTORATE BY RESEARCH).
Thesis Title:
Therapies to reduce brain injury associated with birth asphyxia.
Supervisors:
Miller, S (Main), Jenkin, G (Associate), Wong, F (Associate).

Completed Supervision

Student:
Menidis, C.
Program of Study:
The mechanisms by which prenatal hypoxia impairs memory consolidation in the newly hatched chick. (PHD) 2006.
Supervisors:
Gibbs, M (Joint), Miller, S (Joint-Co).
Student:
Saglam, B.
Program of Study:
Antenatal brain injury and prospects for neuroprotection. (PHD) 2009.
Supervisors:
Miller, S (Joint), Wallace, E (Joint-Co).
Student:
Supramaniam, V.
Program of Study:
Activin A and fetal growth restriction. (PHD) 2005.
Supervisors:
Jenkin, G (Joint-Co), Miller, S (Joint).