Lung Development

Lung Development Research Group

Research Group Head

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).

Research Projects

  • 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.

Research Group

Selected publications

  • Wallace MJ, Probyn ME, Zahra VA, Crossley K, Cole TJ, Davis PJG, Morley CJ, Hooper SB (2009) Early biomarkers and potential mediators of ventilation-induced lung injury in very preterm lambs. Respiratory Research 10: article 19.

  • Hooper SB, Kitchen MJ, Siew ML, Lewis RA, Fouras A, te Pas AB, Siu KKW, Yagi N, Uesugi K, Wallace MJ (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 CE, Hooper SB, Wallace MJ (2010) Partial pulmonary embolization disrupts alveolarization in fetal sheep. Respiratory Research 11: article 42.

  • Siew ML, te Pas AB, Wallace MJ, Kitchen MJ, Islam M, Lewis RA, Fouras A, Morley CJ, Davis PG, Yagi N, Uesugi K, Hooper SB (2011) Surfactant increases the uniformity of lung aeration at birth in ventilated preterm rabbits. Pediatric Research 70(1):50-55.

  • McDougall ARA, Hooper SB, Zahra VA, Sozo F, Cole TJ, Doran T,Wallace MJ (2011) The oncogene TROP2 regulates fetal lung cell proliferation. American Journal of Physiology – Lung Cellular and Molecular Physiology 301: L478-L489.

  • Fouras A, Allison BJ, Kitchen MJ, Dubsky S, Nguyen J, Hourigan K, Siu KKW, Lewis RA, Wallace MJ, Hooper SB (2012) Altered lung motion is a sensitive indicator of regional lung disease. Annals of Biomedical Engineering 40(5):1160-1169.

  • Westover AJ, Hooper SB, Wallace MJ, Moss TJM (2012) Prostaglandins mediate the fetal pulmonary response to intrauterine inflammation. American Journal of Physiology – Lung Cellular and Molecular Physiology 302:L664-678.

  • Bach KP, Kuschel CA, Hooper SB, Bertram J, McKnight S, Peachey SE, Zahra VA, Flecknoe SJ, Oliver M, Wallace MJ, Bloomfield FH (2012) High bias gas flow rates increase lung injury in the ventilated preterm lamb. PLoS ONE 7 (10): article #e47044.

  • Siew ML, Wallace MJ, Allison BJ, Kitchen MJ, te Pas AB, Islam M, Lewis RA, Fouras A, Yagi N, Uesugi K, Hooper SB (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 KI, Wallace MJ, Kitchen MJ, te Pas AB, Fouras A, Lewis RA, Morley CJ, Davis PG, Hooper SB (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 PG, Hart AH, Bagheri-Fam S, Wallace MJ, Dobbie M, Gordon CG, Miller KA, Whittle B, Abud HE, Arkell RM, Cole TJ, Harley VR, Smyth IM, Bertram JF (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 SB, Zahra V, Wallace MJ, Harding R (2013) Mechanical ventilation injury and repair in extremely and very preterm lung. PLoS ONE 8(5):e63905.

  • McDougall ARA, Hooper SB, Zahra VA, Cole TJ, Lo CY, Dolan T, Wallace MJ (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 DG, Wallace MJ, Bhatia R, Schmoelzer GM, Zahra V, Dolan MJ, Hooper SB, David PG (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 MJ, Hooper SB, McDougall ARA. Chapter 8: Role of physical, endocrine and growth factors in lung development. In: The Lung: Development, Aging and the Environment. Ed. R. Harding and K.E. Pinkerton. Elsevier Academic Press London UK. In Press.