Hibbs - Respiratory Immunobiology Laboratory

Chronic lung disease affects millions of people worldwide; it is a leading cause of death in Australia and imposes a huge personal and financial burden. There is a growing appreciation that factors encountered in early-life can have lifelong impacts on respiratory health. These include in-utero exposures, low birth weight, childhood respiratory infections and premature birth. Infants born very prematurely require respiratory support and it is the intersection of the immature lung with these life-saving therapies that can exacerbate the development of an irreversible lung disease known as bronchopulmonary dysplasia. Current treatments for lung diseases are inadequate and do not target the underlying disease processes, and thus, novel ways to prevent disease and support healthy lung development are needed.

Our research

Our lab investigates how the immune system intersects with the lung during development, injury and infection, and studies how these systems are perturbed and contribute to the evolution of chronic respiratory disease. We use experimental models and patient samples to examine how the lung responds to various challenges during the early-life period to maintain homeostasis, and we seek to define the pathways and processes that go awry during disease development. Our overall goal is to identify key pathways or targets for therapeutic intervention to develop new ways to promote normal lung development, control inflammation and restrain pulmonary disease progression.

Every year, millions of babies are born prematurely, beginning life with immature lungs that are not yet ready for respiration. These infants require life-preserving treatments such as supplemental oxygen (hyperoxia), surfactant therapy and glucocorticosteroids; however, these prophylactic actions can promote lung injury by inducing inflammation and oxidative stress and prevent proper lung growth by inhibiting alveolar development and septation. This predisposes to the development of bronchopulmonary dysplasia and then lifelong lung disease is inevitable. By combining clinically relevant animal models and cutting-edge analysis techniques with samples from patients, our work aims to understand how to reduce inflammation and oxidative stress while also maintaining the alveolar epithelial-endothelial interface so that the lung can develop normally.
Before birth, the lung is filled with fluid, which is removed at parturition by the lymphatic vasculature, allowing the lung to inflate and become compliant, enabling ventilation. Failure of this system to develop or function properly, can be lethal. Supplemental oxygen therapy is a life-saving treatment for very premature infants; however, this essential therapy alters the lymphatic system driving dysregulated lymphangiogenesis and lymphatic vessel remodelling leading to fluid accumulation in the lung, which affects lung development and function. Our group integrates molecular, cellular, functional and structural analyses, to define the role of lymphatic vessels in bronchopulmonary dysplasia and lung tissue injury, determine how early changes contribute to lifelong lung disease and identify potential therapeutic targets.
Investigate the role of unconventional T cells in early-life lung development and immunity
Unconventional innate-like T cells (γδ T, NKT, MAIT) are a primary line of immune defense in early life, accumulating in the neonatal lung prior to the emergence of conventional T cells, where they contribute to lung tissue homeostasis. These cells compete for immunological niches in the lung, have overlapping functions to preserve lung tissue physiology, and become dysregulated in respiratory diseases such as chronic obstructive pulmonary disease. They are critically important responders to early-life respiratory infections and the tissue’s response to inflammation and injury where their functions can become imprinted. Using models of bronchopulmonary dysplasia and lung development defects together with appropriate maternal, neonatal and adult infection models, our research aims to characterise the specific interplay between lung tissue injury and/or infection and unconventional T cell phenotype and function, and to determine how early-life factors can alter this T cell network and impact lifelong lung immunity.
The lung lipidome is the complete lipid profile within the lungs that plays an essential role in pulmonary development and health. Key components of the lung lipidome are pulmonary surfactant lipids, which form a complex lipid-protein mixture that covers the alveolar surface, lowering surface tension and preventing alveolar collapse during respiration. Infants born very prematurely lack pulmonary surfactant as the alveolar epithelial cells responsible for surfactant production are immature, and this is a key driver of morbidity and mortality in this patient population. We combine clinically relevant models of bronchopulmonary dysplasia and impaired lung development with patients’ tracheal aspirates alongside pioneering lipid profiling approaches plus lung mechanics and airway function dynamics, to examine precisely how the lipid profile changes during development, in the presence of inflammation and oxidative stress, and during disease progression, and how specific lipid species aid lung development and function.

Meet the team

Laboratory Head

Dr Evelyn Tsantikos (Senior Research Fellow)
Dr Caitlin O’Brien (Postdoctoral Research Fellow)
Mr Ali Shad (Research Staff)
Ms Caren Andrade (PhD student)

Contact details for the lab

If you would like to be involved in our research, study with us, collaborate with us or donate to our research work, we would be pleased to hear from you. Email us at Margaret.Hibbs@monash.edu

Publications View

Selected publications

Tsantikos E, Lau M, Castelino CMN, Maxwell MJ, Passey SL, Hansen MJ, McGregor NE, Sims NA, Steinfort DP, Irving LB, Anderson GP and Hibbs ML. Granulocyte-CSF links destructive inflammation and comorbidities in obstructive lung disease. J Clin Invest 128(6): 2406-2418, 2018.
Wickramasinghe LC, Lau M, Deliyanti D, Gottschalk TA, van Wijngaarden P, Talia D, Johnson C, Wilkinson-Berka JL, Tsantikos E and Hibbs ML. Lung and eye disease develop concurrently in supplemental oxygen-exposed neonatal mice. Am J Path, 190(9): 1801-1812, 2020.
Raftery AL, Tsantikos E, Harris NL and Hibbs ML. Links between inflammatory bowel disease and chronic obstructive pulmonary disease. Front Immunol 11: 2144, 2020.
Tsantikos E, Gottschalk TA, L’Estrange-Stranieri E, O’Brien CA, Raftery AL, Wickramasinghe LC, McQualter JL, Anderson GP and Hibbs ML. Enhanced Lyn activity causes severe, progressive emphysema and lung cancer. Am J Respir Cell Mol Biol. 69(1):99-112, 2023.
Raftery AL, O’Brien CA, Harris NL, Tsantikos E and Hibbs ML. Development of severe colitis is associated with lung inflammation and pathology. Front Immunol. 14:1125260, 2023.
Wickramasinghe LC, Tsantikos E, Kindt A, Gottschalk TA, Borger JG, Malhotra A, Anderson GP, van Wijngaarden P, Hilgendorff A and Hibbs ML. Granulocyte colony-stimulating factor is a determinant of severe bronchopulmonary dysplasia and coincident retinopathy. Am J Path, 193(12): 2001-2016, 2023.
Raftery AL, O’Brien CA, Shad A, L’Estrange-Stranieri E, Hsu AT, Jacobsen EA, Harris NL, Tsantikos E and Hibbs ML. Activated eosinophils in early-life impair lung development and promote long-term lung damage. Mucosal Immunology, 17(5):871-891, 2024.
Hsu AT, O’Donoghue RJJ, Tsantikos E, Gottschalk TA, Borger JG, Gherardin NA, Xu C, Koay HF, Godfrey DI, Ernst M, Anderson GP and Hibbs ML. An unconventional T cell nexus drives HCK-mediated chronic obstructive pulmonary disease in mice. eBioMedicine, 115: 105707, 2025.
L’Estrange-Stranieri E, Gottschalk TA, Kong AM, Maxwell MJ, Pang ES, Tsantikos E, Tarlinton DM, O’Keeffe M, Wright MD and Hibbs ML. Lyn restrains lupus via kinase-independent mechanisms that limit toll-like receptor activation and type I interferon responsiveness. Science Advances, 11(42): eadz1726, 2025.
Wickramasinghe LC*, L’Estrange-Stranieri E*, Cardwell B, O’Brien CA, Shad A, van Wijngaarden P, Anderson GP, Stacker SA, Achen MG, Tsantikos E and Hibbs ML. VEGF-D protects the lung in neonatal hyperoxia-induced lung injury. Am J Respir Cell Mol Biol 73(5): 790-804, 2025.

Department of Immunology

Medicine, Nursing and Health Sciences