Pulmonary Development and Programming Group
Head of Group: Prof Richard Harding
Senior Research Officers: Dr Robert DeMatteo and Dr Foula Sozo
Research Assistant: Natascha Blasch and Victoria Stacy
PhD students: Kelly Kenna, Nadine Brew and Megan O"Reilly
Honours students (2007): Luke O'Day and Megan O'Reilly
The Pulmonary Development and Programming Group
Respiratory illnesses are a major cause of death and disability at all ages, and represent a major cost to the society in terms of medical expenses, lost days of productivity and reduced quality of life. It is now apparent that the risk of respiratory illnesses such as asthma and chronic obstructive lung disease, as well as the rate of the age-related decline in lung function, may be exacerbated as a result of the environment during formation of the lung in fetal and neonatal life. Particular factors that have been identified as having the potential to cause persistent alterations in lung structure and function include fetal growth restriction (eg by placental insufficiency or maternal undernutrition), premature birth, exposure to an inflammatory intra-uterine environment, ventilator-induced lung injury, maternal alcohol ingestion, and respiratory infections during infancy.
The major research interests of the Pulmonary Development and Programming Group are:
1. The role of premature birth in the early developmental origins of cardio-respiratory diseases.
Premature birth is a serious environmental challenge faced by 8-10% of all infants. In preterm infants, many organs are obliged to function before they are fully mature, leading to persistent alterations in their development. This can contribute to life-long impairments in respiratory and neurological function for example. The extent to which altered development is due to preterm birth per se or injury induced by medical supportive procedures is at present unclear. Our studies are aimed at understanding how premature birth alters lung structure through to adulthood, as such information is unavailable from human observations. In collaboration with others we are researching the effects of preterm birth on the development of the cardiovascular system and kidneys.
2. Mechanisms underlying the effects of fetal and postnatal growth restriction on adult lung structure and function.
Restricted growth during fetal and early postnatal life has been shown to cause permanent alterations in lung structure and function. In humans, there is a strong correlation between early growth rates and lung function and lung illnesses. These effects could be related to hypoxia or nutrient restriction during early life. We are currently exploring the mechanisms whereby nutrient availability and growth induce persistent alterations in structural development of the lung parenchyma and conducting airways. In collaborative studies, we are investigating the effects on development of the heart and kidneys.
3. Mechanisms of fetal brain injury caused by hypoxia and/or inflammation: the development of neuroprotective strategies.
As well as injury to the developing lung, we are interested in the aetiology of altered brain development and fetal brain injury resulting from prenatal hypoxia or inflammation. In collaboration with A/Prof S. Rees (University of Melbourne) we are investigating the effects of prenatal hypoxia and inflammation induced by endotoxin exposure on the preterm fetal brain, in particular the sub-cortical and periventricular white matter. Recent studies are aimed at exploring the potential neuroprotective effects of N-acetyl cysteine (NAC) and erythropoietin (EPO) delivered to the preterm fetus.
4. Effects of alcohol exposure on the fetus during late gestation.
In human infants and children the effects of chronic exposure to high levels of alcohol are well defined. However, the effects of intermittent exposures to lower levels of alcohol are less well understood. A number of studies have shown that short exposures or “binges” may be more harmful to the developing brain than chronic exposures. We have recently shown that fetal exposure to 3 short episodes of maternal alcohol ingestion is able to injure the developing white matter. In collaborative studies we are exploring the effects of daily prenatal alchohol exposure on the developing kidney, lungs and heart.
Conferences and workshops
Current Research Grants
“Novel strategies for improving respiratory support and outcomes for very preterm babies”. R Harding, C Morley, S Hooper, P Davis, T Cole. 2006-2010, $7,895,340 over 5 years. NH&MRC, ID: 384100.
“Protecting the preterm fetal brain from hypoxia and infection: a healthy start to life”.
NH&MRC ID: 350307. S Rees, R Harding, M Cock, G Rice. 2005-7. $163,250 per year. NH&MRC, ID: 350307.
“Fetal alcohol syndrome: oxidative stress and innovative therapies”. R Harding, D Walker. Canadian Institutes of Health Research. 2006-7. $86,502 per year.
“Mechanisms of programmed hypertension in twin offspring”. R Harding, M Probyn. Los Angeles Biomedical Research Institute. 2005-6. $66,804.
Recent Publications
Recently Edited Books
Harding R, Pinkerton KE, Plopper CG. (2004) The Lung: Development, Aging and the Environment. Elsevier Academic Press, UK. (27 chapters, 395 pages).
Harding R, Bocking AD. (2001) Fetal Growth and Development, Cambridge University Press, Cambridge, UK. (13 chapters, 283 pages)
Recent Journal Articles, Reviews and Chapters
2007 publications
Gatford KL, PA Dalitz, ML Cock, R Harding, JA Owens. (2007) Acute ethanol exposure inpregnancy alters the insulin-like growth factor axis of fetal and maternal sheep. AmericanJournal of Physiology; Endocrinology and Metabolism. 292: E494-500.
Loeliger M, J Duncan, ML Cock , R Harding, SM Rees. (2007) Vulnerability of dopaminergicamacrine cells and optic nerve myelination to prenatal endotoxin exposure. InvestigativeOphthalmology and Visual Science. 48: 472-478.
Richardson HL, PM Parslow, AM Walker, R Harding, RSC Horne (2007) Maturation of theinitial ventilatory response to hypoxia in sleeping infants. Journal of Sleep Research. 16,117-27.
Feltis BN, D Wignarajah, C Ward, DW Reid, R Harding, EH Walters. (2007) Effects of inhaled fluticasone on angiogenesis and vascular endothelial growth factor in asthma. Thorax 62: 314-9
Bubb KJ, ML Cock, MJ Black, M Dodic WM Boon, HC Parkington, R Harding, M Tare. (2007) Intrauterine growth restriction delays cardiomyocyte maturation and alters coronary artery function in the fetal sheep. Journal of Physiology 578; 871-881.
Crossley KJ, CJ Morley, BJ Allison, GR Polglase, PA Dargaville, R Harding, SB Hooper.(2007) Blood gases and pulmonary blood flow during resuscitation of very preterm lambstreated with antenatal Betamethasone and/or Curosurf: effect of positive end-expiratorypressure. Pediatric Research 62: 37-42.
Maritz GS, M Probyn, R DeMatteo, K Snibson, R Harding. (2007) Lung structure at maturityis influenced by postnatal growth rate but not by moderately preterm birth in sheep.Neonatology 93, 28-35.
Zohdi V, KM Moritz, KJ Bubb, ML Cock, N Wreford, R Harding, MJ Black (2007)Nephrogenesis and the renal renin-angiotensin system in fetal sheep: effects of intrauterinegrowth restriction during late gestation. American Journal of Physiology: Regulatory,Integrative and Comparative 293: R1267-73.
Rees S, Harding R, Walker D. (2007) An adverse intrauterine environment: implications for injury and altered development of the brain. International Journal of DevelopmentalNeuroscience (in press) E-pub September 29, 2007.
Suzuki K, Harding R. (2007) Pulmonary circulation and pulmonary function in neonatal lunghypoplasia: treatment with corticosteroids. Current Pediatric Reviews 3: 264-276.
Thompson B, King G, Harding R. Commentary on "The role of the large airways on smoothmuscle contraction in asthma". J Appl Physiol. 2007;103(4):1465.
DeMatteo R, Stacy V, Probyn M, Desai M, Ross M, Harding R The perinataldevelopment of arterial pressure in sheep: effects of low birthweight due to twinning.Reproductive Sciences (in press)
Probyn ME, Stacy V, Desai M, Ross M, Harding R. Fetal weight differences within the normal range do not affect blood pressure, the HPA axis and the renin-angiotensin system in the late gestation ovine fetus. Reproduction, Fertility and Development (in press)
Harding R. Long-term effects of preterm birth and early nutrition on predisposition to later lung disease. Pediatric Respiratory Review (in press)
Harding R, Snibson K, Maritz GS. Early environmental influences on lung development: Implications for lung function and respiratory health throughout life. In: “DOHAD conference proceedings” Eds MG Ross and JP Newnham. Karger, Basel (in press).
Harding R, SB Hooper. Physiologic mechanisms of normal and altered lung growthbefore and after birth. In: Fetal and Neonatal Physiology; Fourth edition, Edited by R. Polin,W. Fox and S. Abman. Published by Elsevier Science / W.B. Saunders. (in press)
Harding R, SB Hooper. Lung growth and maturation. In: Fetal Medicine: BasicScience & Clinical Practice, 2nd edition; eds C Rodeck and M Whittle. Elsevier UK (in press)
Snibson K, Harding R. Postnatal growth rate but not mild preterm birth influencesairway structure in adult sheep challenged with house dust mite. Experimental LungResearch (in press).
2006 publications
Sozo F, MJ Wallace, MR Hanna, SJ Flecknoe, ML Cock, GS Maritz, R Harding, SB. Hooper (2006). Alveolar epithelial cell differentiation and surfactant protein mRNA following mild preterm birth. Pediatric Research 59:151-6.
Duncan JR, ML Cock, K Suzuki, J-P Y Scheerlinck, R Harding, S M Rees. (2006) Chronic endotoxin exposure causes brain injury in the ovine fetus in the absence of hypoxemia. Journal of the Society for Gynecologic Investigation. 13: 87-96.
Harding R, Cock ML, Maritz GS. (2006). The developmental environment: effects on lung structure and function. In: Developmental Origins of Health and Disease. Editors: P Gluckman and M. Hanson. Cambridge University Press, UK. p336-348.
Rees S, Inder, T and Harding R. (2006). The developmental environment and the origins of neurological disorders. In: Developmental Origins of Health and Disease. Eds: P Gluckman & M.Hanson. Cambridge University Press, UK. p379-391.
Briscoe T, Duncan J, Cock ML, Choo J, Rice G, Harding R, Scheerlinck J-P, Rees S. (2006) Activation of nf-Kb transcription factor in the preterm ovine brain and placenta after acute LPS-exposure. Journal of Neuroscience Research 83: 567-574.
Richardson HL, Parslow PM, Walker AM, Harding R, Horne RSC. (2006) Variability of the initial phase of the ventilatory response to hypoxia in sleeping infants. Pediatric Research 59; 700-704.
Harding R, CA Albuquerque, SB Hooper (2006). Fetal breathing: In Encyclopedia ofRespiratory Medicine. Eds: G. Laurent and D. Shapiro, Elsevier. 242-246.
Harding R, SB Hooper, MJ Wallace (2006). Lung development: overview, In: Encyclopediaof Respiratory Medicine. Eds: G. Laurent and D. Shapiro, Elsevier, 613-620.
Hooper SB and Harding R (2006). Fetal lung liquid, In Encyclopedia of Respiratory Medicine.Eds: G. Laurent and D. Shapiro, Elsevier 246-250.
Harding R and KE Pinkerton (2006). Lung anatomy (Including the aging lung), InEncyclopedia of Respiratory Medicine. Eds: G. Laurent and D. Shapiro, Elsevier, 606-612.
Feltis B, D Wignarajah, L Zheng, C Ward, D Reid, R Harding, E. H. Walters. (2006)Increased vascular endothelial growth factor and receptors: relationship toangiogenesis in asthma. American Journal of Respiratory and Critical Care Medicine 173:1201-1207.
Brace RA, CY Cheung, LE Davis, R Gagnon, R Harding, JA Widness. (2006) Sources ofamniotic fluid erythropoietin during normoxia and hypoxia in fetal sheep. American Journal ofObstetrics and Gynecology. 195: 246-254.
Nitsos I, SM Rees, J Duncan, BW Kramer, R Harding, JP Newnham, TJM Moss. (2006)Chronic exposure to intra-amniotic lipopolysaccharide affects the ovine fetal brain. Journal ofthe Society for Gynecologic Investigation, 13, 239-247.
Suzuki K, MJ Wallace, ME Probyn, SB Hooper, R Harding. (2006) Effects of antenatalcorticosteroids on pulmonary ventilation and circulation in neonatal lambs with hypoplasticlungs. Pediatric Pulmonology, 41; 844-854.
Snibson KJ, LS McMurtrie, RJ Bischof, E Koumoundouros, ML Cock, R Harding. (2006)Altered airway responsiveness in adult sheep born prematurely: effects of allergen exposure.Experimental Lung Research, 32: 215-228.
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