Professor Peter Sly

Senior Clinical Research Fellow

Child Health Research Centre
Faculty of Medicine and Biomedical Sciences
p.sly@uq.edu.au
+61 7 3069 7383

Overview

Professor Peter Sly is the Director, Children's Health and Environment Program and Director, WHO Collaborating Centre for Children's Health and Environment. Professor Sly is a NHMRC Senior Principal Research Fellow and a paediatric respiratory physician with extensive research experience in respiratory physiology, developmental immunology and children's environmental health. Professor Sly’s research aims to understand the mechanisms underlying chronic childhood lung diseases in order to improve clinical management and to delay or prevent their onset, with consequent reductions in adult lung diseases. A combination of basic science, longitudinal cohort studies and translation of research findings into clinical practice, including clinical trials, are included in three main areas: asthma, cystic fibrosis and children’s environmental health

Professor Sly is the chairman of the board of directors for the Pacific Basin Consortium for the Environment and Health and currently serves on International Advisory Boards and committees, including: WHO Public Health and Environment; WHO network of Collaborating Centres in Children’s Environmental Health; Canadian Healthy Infant Longitudinal Development (CHILD) Study, Canada; and the Infant Lung Health Study, Paarl, South Africa.

Research Interests

  • Asthma
    Understanding mechanisms that underlie risks for developing asthma in susceptible children
  • Cystic Fibrosis
    Understanding the mechanisms underlying the development of lung disease early in life and why and how this progresses
  • Impact of environmental exposures in early life
    Improving methods of assessing environmental exposures during fetal development and in early postnatal life. Improving methods for assessing the effects of early life environmental exposures and understanding how these increase long-tern risk of chronic disease.

Qualifications

  • Doctor of Medicine, University of Melbourne
  • Doctor of Science, The University of Western Australia
  • Bachlor of Medicine and Surgery, University of Melbourne

Publications

View all Publications

Supervision

View all Supervision

Available Projects

  • Macrophages are key cells in innate immune responses and play important roles in both the initiation and resolution of pulmonary inflammation Macrophages recruited to the lungs by inflammatory stimuli are of bone marrow origin, differentiate from monocytes (monocyte-derived macrophages, M0) and polarize into pro-inflammatory (classically activated or M1) or inflammation-resolving (alternatively activated or M2) phenotypes. The initial response to acute lung injury sees the influx of neutrophils, peaking on day 2-3, followed by recruitment of M1 macrophages, peaking on day 6-12. Thereafter resolution of inflammation is facilitated by M2 macrophages over the next 10 days or so. Given the important role played by macrophages in both initiation and resolution of pulmonary inflammation, there has been surprisingly little research in cystic fibrosis (CF) dedicated to macrophages. Much of what has been undertaken has used mouse models; unfortunately major differences between mouse and human macrophages have made interpretation of such studies difficult. We have developed an ex-vivo model of human macrophages that reliably separates un-polarized (M0), M1 and M2 macrophages and generated preliminary data that suggest the activation of M1 macrophages is exaggerated during acute pulmonary exacerbations in both adults and children with CF in a non-CFTR-dependent fashion when compared to the same patients when clinically stable and to healthy subjects. Furthermore, we saw a CFTR-dependent deficiency of M2 macrophages in patients with CF. We plan to undertake a systematic study to determine whether defective macrophage function in CF impairs resolution of pulmonary inflammation and predisposes to progressive lung disease.

    Specific Aims and hypotheses:

    Aim 1: To determine the mechanisms by which M2 macrophages are low in number and deficient in function in CF. We hypothesize that a CFTR-dependent mechanism limits differentiation of precursor monocytes into M2 macrophages in patients with CF.

    Aim 2: To determine the mechanisms by which M0 macrophages are pre-primed into the M1 phenotype, especially during acute pulmonary exacerbations in CF. We hypothesize that the inflammatory milieu in both the blood and the lung results in a greater proportion of monocytes that preferentially differentiate into the pro-inflammatory M1 phenotype.

    Aim 3: To determine whether monocyte abnormalities are responsible for the abnormal pattern of differentiation and polarization of macrophages in CF. We hypothesize that circulating CF monocytes are deficient in expression of MMP28 and/or CD16 which inhibits polarization into M2 macrophages.

    Aim 4: To determine whether correction of the CFTR dysfunction using CFTR correctors or potentiators or common therapies used in CF and known to modify CFTR location and/or function can restore the ability of monocytes to differentiate and polarize into the inflammation resolution M2 phenotype. We hypothesize that restoring CFTR function will overcome the CFTR-dependent deficiency of M2 macrophages.

View all Available Projects

Publications

Book

  • Pediatric respiratory medicine. Edited by L. M. Taussig, L. I. Landau, LeSouef, P. N., Martinez, F. D., Morgan, W. J. and Sly, P. D. St Louis, USA: Mosby, 1999.

  • Infant Respiratory Function Testing. Edited by J. Stocks, P. D. Sly, R. S. Tepper and W. J. Morgan New York: John Wiley & Sons, 1996.

Book Chapter

  • Sly, Peter D. and Jones, Carmen M. (2012). New and future developments of therapy for asthma in children. In Kai-Håkon Carlsen and Jorrit Gerritsen (Ed.), Paediatric Asthma (pp. 224-234) Lausanne, Switzerland: European Respiratory Society. doi:10.1183/1025448x.10018310

  • Sly, P. D., Kusel, M., Franklin, P. and Holt, P. G. (2011). Environmental factors in children’s asthma and respiratory effects. In Jerome O. Nriagu (Ed.), Encyclopedia of environmental health (pp. 367-379) Amsterdam, Netherlands: Elsevier Science. doi:10.1016/B978-0-444-52272-6.00018-0

  • Calogero, C. and Sly, P. D. (2010). Developmental physiology : Lung function during growth and development from birth to old age. In Paediatric lung function (pp. 1-15) Shieffield, United Kingdom: European Respiratory Society. doi:10.1183/1025448x.00011109

  • Sly, Peter and Collins, Rachel A. (2008). Applied clinical respiratory physiology. In Lynn M. Taussig, Louis I. Landau, Peter N. Le Souëf, Fernando D. Martinez, Wayne J. Morgan and Peter D. Sly (Ed.), Pediatric respiratory medicine 2nd ed. (pp. 73-88) Philadelphia PA: Mosby/Elsevier.

  • Sly, Peter, Holt, Patrick G., Stein, Renato T. and Martinez, Fernando D. (2008). Disease mechanisms and cell biology. In Lynn M. Taussig, Louis I. Landau, Peter N. Le Souëf, Fernando D. Martinez, Wayne J. Morgan and Peter D. Sly (Ed.), Pediatric respiratory medicine 2nd ed. (pp. 791-804) Philadelphia PA: Mosby/ Elsevier.

  • Sly, Peter, Collins, Rachel A. and Morgan, Wayne J. (2008). Lung function in cooperative subjects. In Lynn M. Taussig, Louis I. Landau, Peter N. Le Souëf, Fernando D. Martinez, Wayne J. Morgan and Peter D. Sly (Ed.), Pediatric respiratory medicine 2nd ed. (pp. 171-178) Philadelphia PA: Mosby/ Elsevier.

  • Sly, Peter and Morgan, Wayne J. (2008). Respiratory function testing in infants and preschool children. In Lynn M. Taussig, Louis I. Landau, Peter N. Le Souëf, Fernando D. Martinez, Wayne J. Morgan and Peter D. Sly (Ed.), Pediatric respiratory medicine 2nd ed. (pp. 163-170) Philadelphia PA: Mosby/ Elsevier.

  • Holt, Patrick G., Sly, Peter and Devereux, Graham (2006). Early life origins of allergy and asthma. In Stephen T. Holgate, Martin K. Church and Lawrence M. Lichtenstein (Ed.), Allergy 3rd ed. (pp. 223-231) Philadelphia, PA , United States: Mosby Elsevier.

  • Douglas T and Sly, Peter (2006). Unique biological characteristics of children; Developmental stage-specific susceptibilities and outcomes in children. In Principles for evaluating health risks in children associated with exposure to chemicals (pp. 22-128) Geneva: World Health Organisation.

  • Sly, Peter and Flack, F. S. (2005). Monitoring childhood asthma. In Peter G. Gibson (Ed.), Monitoring asthma (pp. 363-382) Boca Raton, U.S.: Taylor & Francis.

  • Sly, Peter, Flack, F. S. and Hantos, Z. (2005). Respiratory mechanics in infants and children. In Outayba Hamid, Joanne Shannon and James Martin (Ed.), The physiological basis of respiratory disease (pp. 49-54) Hamilton, Ontario, Canada: B.C. Decker.

  • Burton, Paul, Gurrin, Lyle and Sly, Peter (2004). Extending the simple linear regression model to account for correlated responses: An introduction to generalized estimating equations and multilevel mixed modelling. In Ralph B. D'Agostino (Ed.), Tutorials in biostatistics (pp. 1-33) Chichester, West Sussex, United Kingdom: John Wiley & Sons. doi:10.1002/0470023724

Journal Article

Conference Publication

Grants (Administered at UQ)

PhD and MPhil Supervision

Current Supervision

  • Doctor Philosophy — Principal Advisor

  • Doctor Philosophy — Principal Advisor

    Other advisors:

  • Doctor Philosophy — Associate Advisor

    Other advisors:

  • Doctor Philosophy — Associate Advisor

    Other advisors:

  • Doctor Philosophy — Principal Advisor

    Other advisors:

  • Doctor Philosophy — Principal Advisor

  • Doctor Philosophy — Associate Advisor

    Other advisors:

  • Doctor Philosophy — Associate Advisor

    Other advisors:

  • Doctor Philosophy — Associate Advisor

    Other advisors:

  • Doctor Philosophy — Associate Advisor

    Other advisors:

  • Doctor Philosophy — Associate Advisor

    Other advisors:

Completed Supervision

Possible Research Projects

Note for students: The possible research projects listed on this page may not be comprehensive or up to date. Always feel free to contact the staff for more information, and also with your own research ideas.

  • Macrophages are key cells in innate immune responses and play important roles in both the initiation and resolution of pulmonary inflammation Macrophages recruited to the lungs by inflammatory stimuli are of bone marrow origin, differentiate from monocytes (monocyte-derived macrophages, M0) and polarize into pro-inflammatory (classically activated or M1) or inflammation-resolving (alternatively activated or M2) phenotypes. The initial response to acute lung injury sees the influx of neutrophils, peaking on day 2-3, followed by recruitment of M1 macrophages, peaking on day 6-12. Thereafter resolution of inflammation is facilitated by M2 macrophages over the next 10 days or so. Given the important role played by macrophages in both initiation and resolution of pulmonary inflammation, there has been surprisingly little research in cystic fibrosis (CF) dedicated to macrophages. Much of what has been undertaken has used mouse models; unfortunately major differences between mouse and human macrophages have made interpretation of such studies difficult. We have developed an ex-vivo model of human macrophages that reliably separates un-polarized (M0), M1 and M2 macrophages and generated preliminary data that suggest the activation of M1 macrophages is exaggerated during acute pulmonary exacerbations in both adults and children with CF in a non-CFTR-dependent fashion when compared to the same patients when clinically stable and to healthy subjects. Furthermore, we saw a CFTR-dependent deficiency of M2 macrophages in patients with CF. We plan to undertake a systematic study to determine whether defective macrophage function in CF impairs resolution of pulmonary inflammation and predisposes to progressive lung disease.

    Specific Aims and hypotheses:

    Aim 1: To determine the mechanisms by which M2 macrophages are low in number and deficient in function in CF. We hypothesize that a CFTR-dependent mechanism limits differentiation of precursor monocytes into M2 macrophages in patients with CF.

    Aim 2: To determine the mechanisms by which M0 macrophages are pre-primed into the M1 phenotype, especially during acute pulmonary exacerbations in CF. We hypothesize that the inflammatory milieu in both the blood and the lung results in a greater proportion of monocytes that preferentially differentiate into the pro-inflammatory M1 phenotype.

    Aim 3: To determine whether monocyte abnormalities are responsible for the abnormal pattern of differentiation and polarization of macrophages in CF. We hypothesize that circulating CF monocytes are deficient in expression of MMP28 and/or CD16 which inhibits polarization into M2 macrophages.

    Aim 4: To determine whether correction of the CFTR dysfunction using CFTR correctors or potentiators or common therapies used in CF and known to modify CFTR location and/or function can restore the ability of monocytes to differentiate and polarize into the inflammation resolution M2 phenotype. We hypothesize that restoring CFTR function will overcome the CFTR-dependent deficiency of M2 macrophages.