Welcome to the Molecular and Integrative Cystic Fibrosis (miCF) Research Centre ®. Our lab is interested in understanding the cellular and molecular processes involved in the regulation of epithelial cell biology and how the breakdown of this regulation leads to pathogenesis of disease such as Cystic Fibrosis.
We are based at the Westfield Research Laboratories at the Sydney Children's Hospital, Randwick. We have a range of specialised equipment to facilitate our research efforts such as digital and confocal microscopy and multiple ultra-freezers that are used for biobanking services. The lab is well-equipped and configured to support a wide range of experiments making it possible to perform cytogenetic, epigenetics, and molecular and cell biology research.
We have access to world class genomics and proteomics facilities based at UNSW Kensington, who assist us with all our sequencing and mass spectrometry needs. We also have a strong affiliation and collaboration with the Drug Discovery Centre at the Children's Cancer Institute of Australia, where we test and develop our new small molecule therapies.
We welcome highly motivated and creative individuals to join the lab. If you are interested in any of the projects listed below please contact the appropriate person listed at the end of each project description. Expressions of interest with a curriculum vitae can be sent to Professor Adam Jaffe.
> Creating model systems for precision medicine
We are using an exciting and cutting edge technology to grow stem cell-derived human ‘mini organs’ (organoids) from the tissues of patients with CF. These organoids are characterised by genome sequencing, expression profiling and sensitivity to known drugs. By recording and analysing this information we can predict a patient’s response to pre-clinical and clinical drugs, allowing us to rapidly develop effective treatments tailored to individuals.
We are currently running a study to find out people’s perceptions about avatar/organoid technology. If you wish to read more about this study, please visit the Sydney Children’s Hospitals Network Clinical trials page. Contact: Dr Shafagh Waters
> MATRIX-CF: Modelling the Alimentary Tract using ex-vivo systems in Cystic Fibrosis study
The primary aim of this project is to culture an intestinal organoid model of CF and healthy control patients, and to then use these models to compare the responses of each to microbial communities.These can then be used to observe the complex interactions between host (genetic, immune and mucosal) factors, microbial communities and intestinal inflammation. Secondary aims are to test the effects of drugs or interventions which have theoretical or potential anti-inflammatory effects on the intestinal model in CF. Contact: Dr Shafagh Waters or Dr Keith Ooi
> RNA-targeted activation of CFTR
The overall goal of this project is to identify intrinsic molecules that disrupt production of the CFTR protein in the cell. We have identified one such molecule and our aim is to find out its prevalence in people with CF. Contact: Dr Shafagh Waters
> PEARL-CF: Probiotics and early-life effects on intestinal bacteria and inflammation
This study focuses on the unique environment that exists in the gastrointestinal tract of children with cystic fibrosis, paying close attention to changes in gut microbiota and the development of intestinal inflammation. Work is concentrated on trying to understand the way the disease develops, its clinical impact and potential therapies. Contact: Dr Keith Ooi
> DISH-CF: Dietary Intake Study in children with Cystic Fibrosis
This study evaluates the dietary intake of children with Cystic Fibrosis. Ideally, this will lead to the identification of optimal eating patterns to support health and wellbeing, and inform future global nutritional recommendations in Cystic Fibrosis. Contact: Dr Keith Ooi
> EOS-CFRD: Early Origins Study of Cystic Fibrosis-related Diabetes study
Some children with Cystic Fibrosis eventually develop Cystic Fibrosis-related Diabetes, however very little is known about how diabetes develops over time. This study examines the glucose levels of young children to get a better understanding of diabetes in Cystic Fibrosis, and aims to facilitate its early detection. Contact: Dr John Widger or Dr Bernadette Prentice
> INSPPIRE: International Study Group of Pediatric Pancreatitis
In association with the Early Origins Study of Cystic Fibrosis-related diabetes (above), we hope to better understand pancreatitis in children and to develop better tests and treatments.INSPPIRE is a group of 21 paediatric gastroenterology centres in the United States, Canada, Israel, and Australia. Contact: Dr Keith Ooi
> Serum biomarkers of Cystic Fibrosis-related Diabetes
This project aims to detect biomarkers that can be used to identify individuals with CF at risk of developing complications such as cystic fibrosis-related diabetes. This would result in more accurate predictions and improve the care and long-term outcomes of CF patients. Contact: Dr Shafagh Waters or Dr John Widger
> CF-IDEA: Cystic Fibrosis – Insulin Deficiency, Early Action Trial
The CF-IDEA trial (Cystic Fibrosis – Insulin Deficiency, Early Action) aims to determine whether starting insulin treatment before the onset of diabetes (earlier than current practice) will improve the health of children with Cystic Fibrosis by improving body weight and lung function. Contact: Dr Shafagh Waters or Dr John Widger
> Harnessing the protective functions of stress granules in CF
Stress granules contribute to cell survival and are formed in response to certain cellular stress. In this study we test if the oxidative stress caused by CF contributes to cell death in epithelial cells, such as those lining the respiratory and gastrointestinal tracts, by inhibiting stress granule formation. Compounds that promote stress granules will also be assessed. Contact: Dr Shafagh Waters or Dr John Widger
The research team
Professor Adam Jaffe, Group Leader
Adam is a Respiratory Physician at Sydney Children's Hospital and Head of Paediatrics at the School of Women's and Children's Health, UNSW. He has many research interests, including developing new medications which may help reduce the destructive build-up of sputum in the airways of children with CF. More information can be found on Adam's academic profile page.
Dr John Widger, Head of Department, Respiratory Medicine, Sydney Children's Hospital
John is a Paediatric Respiratory and Sleep Consultant and is the Director of Paediatric Respiratory medicine at Sydney Children’s Hospital Randwick. He is also a conjoint senior lecturer at the University of New South Wales. John's research interests are in obstructive sleep apnoea, cystic fibrosis and asthma.
Dr Keith Ooi, Paediatric Gastroenterologist
Keith is a translational clinician investigator with research interests and expertise in gastroenterological conditions in cystic fibrosis, diagnostic dilemmas, non-classic manifestations of CF and childhood pancreatic diseases. He is Senior Lecturer within the School of Women’s and Children’s Health, UNSW. More information can be found on Keith's academic profile page.
Dr Shafagh Waters, Senior Research Associate
Shafagh is passionate about molecular research with clinically applicable outcomes. Her main research project has a strong translational focus and aims to discover small molecules and peptides that are effective in correcting the functional defects exhibited by CFTR mutation, while addressing the variability between individuals. More information can be found on Shafagh's academic profile page.
| Dr Yvonne Belessis, Director of Cystic Fibrosis services, Sydney Children's Hospital
Yvonne's main field of research is early airway infection and inflammation in children with cystic fibrosis, with a particular interest in biomarkers of early CF lung disease. More information can be found on Yvonne's academic profile page.
|Other team members:|
The School Experiences of Siblings of Children With Chronic Illness: Australian Parents’ Perceptions, Gan LL; Lum A; Wakefield CE; Donnan BM; Marshall GM; Burns MA; Jaffe A; Leach S; Lemberg DA; Fardell JE, 2018, Educational and Developmental Psychologist, pp. 1 - 15
Probiotics for people with cystic fibrosis Coffey MJ; Garg M; Homaira N; Jaffe A; Ooi CY, 2018, Cochrane Database of Systematic Reviews, vol. 2018
Age-related levels of fecal M2-pyruvate kinase in children with cystic fibrosis and healthy children 0 to 10 years old, Garg M; Leach ST; Pang T; Needham B; Coffey MJ; Katz T; Strachan R; Widger J; Field P; Belessis Y; Chuang S; Day AS; Jaffe A; Ooi CY, 2018, Journal of Cystic Fibrosis, vol. 17, pp. 109 - 113
Rare disease registries: a call to action, Lacaze P; Millis N; Fookes M; Zurynski Y; Jaffe A; Bellgard M; Winship I; McNeil J; Bittles AH, 2017, Internal Medicine Journal, vol. 47, pp. 1075 - 1079
Age-dependent variation of fecal calprotectin in cystic fibrosis and healthy children, Garg M; Leach ST; Coffey MJ; Katz T; Strachan R; Pang T; Needham B; Lui K; Ali F; Day AS; Appleton L; Moeeni V; Jaffe A; Ooi CY, 2017, Journal of Cystic Fibrosis, vol. 16, pp. 631 - 636,
Association of rhinovirus with exacerbations in young children affected by cystic fibrosis: Preliminary data, Stelzer-Braid S; Liu N; Doumit M; D'Cunha R; Belessis Y; Jaffe A; Rawlinson WD, 2017, Journal of Medical Virology, vol. 89, pp. 1494 - 1497,
Question 5: What is the role of macrolide antibiotics as anti-inflammatory treatment in Cystic fibrosis?, Fitzgerald NM; Jaffe A, 2016, Paediatric Respiratory Reviews, vol. 18, pp. 55 - 57
Resolution of intestinal histopathology changes in cystic fibrosis after treatment with ivacaftor, Safe M; Gifford AJ; Jaffe A; Ooi CY, 2016, Annals of the American Thoracic Society, vol. 13, pp. 297 - 298
Is there a role for stool metabolomics in cystic fibrosis?, Kaakoush NO; Pickford R; Jaffe A; Ooi CY, 2016, Pediatrics International, vol. 58, pp. 808 - 811
Diagnosing cystic fibrosis-related diabetes: current methods and challenges, Prentice B; Hameed S; Verge CF; Ooi CY; Jaffe A; Widger J , 2016, Expert Review of Respiratory Medicine, vol. 10, pp. 799 - 811
Disrupted progression of the intestinal microbiota with age in children with cystic fibrosis Nielsen S; Needham B; Leach ST; Day AS; Jaffe A; Thomas T; Ooi CY, 2016, Scientific Reports, vol. 6
Diagnostic accuracy and distress associated with oropharyngeal suction in cystic fibrosis, Doumit M; Belessis Y; Stelzer-Braid S; Mallitt KA; Rawlinson W; Jaffe A, 2016, Journal of Cystic Fibrosis, vol. 15, pp. 473 - 478,
A pilot study of inhaled dry-powder mannitol during cystic fibrosis-related pulmonary exacerbation, Middleton A; Robinson PD; McKay K; Jaffe A; Selvadurai H, 2015, European Respiratory Journal, vol. 45, pp. 541 - 544,
Advances in the detection and management of cystic fibrosis related diabetes, Hameed S; Jaffé A; Verge CF, 2015, Current Opinion in Pediatrics, vol. 27, pp. 525 - 533