– Amnion Cell Biology
– Cell Therapy and Regenerative Medicine
– Embryology and Placental Biology
– Endometrial Stem Cells
– Epidemiology and Clinical Trials
– Fetal and Neonatal Health
– Infant and Child Health
– Interventional Immunology in Neonatal Diseases
– Lung Development
– Maternal and Perinatal Medicine
– Neurodevelopment and Neuroprotection
– Perinatal Inflammation
– Perinatal Transition
– Respiratory Control
Research > The Ritchie Centre > Lung Development
Research Group Head: Dr Megan Wallace
Many events during fetal and early postnatal life can affect lung development with life-long consequences. Our aim is to determine the mechanisms that regulate normal lung development and that lead to perturbed lung development.
The lung undergoes an incredible transition at birth because the placenta exchanges gases during fetal life, but the moment the umbilical cord is cut, the lung must take on the role of gas exchange, a role that it has never performed before. If the lung does not exchange gases adequately, the infant may die or suffer significant damage to the lungs, brain and other organs.
Babies that are born prematurely, or that have failed to reach their growth potential (fetal growth restriction) are born before the lungs are adequately developed. As a result, they often require assisted ventilation, which is necessary for their survival but it can injure the lungs and cause them to develop abnormally. This abnormal lung development is called Bronchopulmonary Dysplasia (BPD).
- Identifying the mechanisms that regulate normal lung development, so that we can manipulate those mechanisms to accelerate lung development
- Identifying the mechanisms by which lung injury leads to BPD, so that we can develop new therapeutic strategies to interfere with those mechanisms, preventing BPD
- Identifying biomarkers to determine which babies sustain lung injury at birth and are at most risk of developing BPD; these are the babies that will require the treatments identified in (2)
- Identifying more gentle strategies for respiratory support that reduce lung injury at birth, which should reduce the incidence of BPD.
Dr Megan Wallace (Research Group Head)
Wallace M.J., Probyn M.E., Zahra V.A., Crossley K., Cole T.J., Davis P.J.G., Morley C.J. and Hooper S.B. (2009) Early biomarkers and potential mediators of ventilation-induced lung injury in very preterm lambs. Respiratory Research 10: article 19
Hooper S.B., Kitchen M.J., Siew M.L., Lewis R.A., Fouras A., te Pas A.B., Siu K.K.W., Yagi N., Uesugi K. and Wallace M.J. (2009) Imaging lung aeration and lung liquid clearance at birth using phase contrast X-ray imaging. Clinical and Experimental Pharmacology and Physiology: Frontiers in research review. 36: 117-125.
Filby C.E., Hooper S.B. and Wallace M.J. (2010) Partial pulmonary embolization disrupts alveolarization in fetal sheep. Respiratory Research 11: article 42
Siew M.L, te Pas A.B., Wallace M.J., Kitchen M.J., Islam M., Lewis R.A., Fouras A., Morley C.J., Davis P.G., Yagi N., Uesugi K. and Hooper S.B. (2011) Surfactant increases the uniformity of lung aeration at birth in ventilated preterm rabbits Pediatric Research 70(1): 50-55
McDougall A.R.A., Hooper S.B., Zahra V.A., Sozo F., Cole T.J., Doran T.and Wallace M.J. The oncogene TROP2 regulates fetal lung cell proliferation. (2011) American Journal of Physiology – Lung Cellular and Molecular Physiology 301: L478-L489.
Fouras A., Allison B.J., Kitchen M.J., Dubsky S., Nguyen J., Hourigan K., Siu K.K.W., Lewis, R.A., Wallace M.J. & Hooper S.B. (2012) Altered lung motion is a sensitive indicator of regional lung disease. Annals of Biomedical Engineering 40(5): 1160-1169
Westover A.J., Hooper S.B., Wallace M.J. and Moss T.J.M. (2012) Prostaglandins mediate the fetal pulmonary response to intrauterine inflammation. American Journal of Physiology – Lung Cellular and Molecular Physiology 302: L664-678
Bach K.P., Kuschel C.A., Hooper S.B., Bertram J., McKnight S., Peachey S.E., Zahra V.A., Flecknoe S.J., Oliver M., Wallace M.J., Bloomfield F.H. (2012) High bias gas flow rates increase lung injury in the ventilated preterm lamb. PLoS ONE 7 (10): article # e47044.
Siew M.L, Wallace M.J., Allison B.J., Kitchen M.J., te Pas A.B., Islam M., Lewis R.A., Fouras A., Yagi N., Uesugi K. and Hooper S.B. (2013) The role of lung inflation and sodium transport in airway liquid clearance during lung aeration in newborn rabbits. Pediatric Research 73: 443-449.
Wheeler K.I., Wallace M.J., Kitchen M.J., te Pas A.B., Fouras A., Lewis R.A., Morley C.J., Davis P.G and Hooper S.B. (2013) Establishing lung gas volumes at birth: The interaction between positive end expiratory pressure and tidal volumes in preterm rabbits. Pediatric Research 73: 734-741
Caruana G., Farlie P.G., Hart A.H., Bagheri-Fam S., Wallace M.J., Dobbie M., Gordon C.G., Miller K.A., Whittle B., Abud H.E, Arkell R.M., Cole T.J., Harley V.R., Smyth I.M. and Bertram J.F. (2013) Genome-wide ENU mutagenesis in combination with high density SNP analysis and exome sequencing provides a rapid route to the identification of novel mouse models of developmental disease. PLoS ONE 8(3): e55429
Brew N., Hooper S.B., Zahra V., Wallace M.J. and Harding R. (2013) Mechanical ventilation injury and repair in extremely and very preterm lung. PLoS ONE 8(5): e63905
McDougall A.R.A., Hooper S.B., Zahra V.A., Cole T.J., Lo C.Y., Dolan T. and Wallace M.J. (2013) TROP2 regulates motility and lamellipodia formation in cultured fetal lung fibroblasts. American Journal of Physiology – Lung Cellular and Molecular Physiology. 305: L508-L521. doi: 10.1152/ajplung.00160.2012
Tingay D.G., Wallace M.J., Bhatia R., Schmoelzer G.M., Zahra V., Dolan M.J., Hooper S.B. and David P.G. (2013) Surfactant before the first inflation at birth improves spatial ventilation and reduces lung injury. Journal of Applied Physiology. 116: 251-258. doi:10.1152/japplphysiol.01142.2013
Wallace M.J., Hooper S.B and McDougall A.R.A. Chapter 8: Role of physical, endocrine and growth factors in lung development. In: The Lung: Development, Aging and the Environment. Ed. R. Harding & K.E. Pinkerton. Elsevier Academic Press, London UK. In Press.