Dr Nathan Rout-Pitt
Grant funded researcher (B)
Adelaide Medical School
Faculty of Health and Medical Sciences
Eligible to supervise Masters and PhD (as Co-Supervisor) - email supervisor to discuss availability.
I I completed my PhD at the University of Adelaide in 2015 with a focus on bone disease in the group of lysosomal storage disorders, Mucopolysaccharidoses.
In late 2015, I joined the CF Airway Research Group (CFARG) where I lead the vector production core and have produced lentiviral vectors for CFARG and Australia-wide laboratories. During this time I have developed and published a method to scale up vector production by as much as 5x. I also developed and published methods for bronchoscopic delivery of liquids such as lentiviral vectors, cells and drugs to single lobes of rat lungs.
In 2018 I began investigating airway remodelling and fibrosis development in CF lungs. A $75,000 Women's and Children's foundation grant allowed me to begin exploring the alterations in cellular architecture of our D508 and 510X CF rat models and their sensitivity to the process of epithelial-mesenchymal transition, which under chronic inflammatory conditions leads to fibrosis.
I briefly left CFARG for a year (2021) to return to lysosomal storage disorders and bone disease, this time looking at Gaucher disease before returning. Upon my return, I have continued with my previous investigations into the developmental/mechanistic pathways leading to lung fibrosis in CF. I have now begun a new project investigating CF bone disease (CFBD) which typically presents with decreased bone mineral volume and short stature and higher risk of fractures. Decreased trabecular number around the growth plate of long bones and previously reported issues at the hypertrophic zone, there is a need to better understand mechanisms at play in the growth plate that could be leading to CFBD.
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Honours projects currently available
Project 1
Title: Identifying altered pathways that lead to increased lung stiffness in CF rats models
Description: Our group has access to two CF rat models containing different mutations (A Phe508del mutation which results in misfolded version of the protein, and a KO mutation with a truncated non-functional protein). CF rat models typically do not develop overt lung disease like humans, however, our newer data suggests that there is evidence of more subtle alterations to the lungs of our CF rat models including lung stiffness; a sign of fibrotic tissue. We have also shown that the gene expression profiles of these two CF rat models are not only different to wildtype rats, but also each other. One of the more obvious changes is collagen type 1 production which is increased in Phe508del rats, but decreased in KO rats.
There are currently a number of sub-projects within this project looking at:
1) Further characterising changes in signalling pathways in these rats using RNAseq,
2) Understanding the effect of Phe508del mutant CFTR protein on signalling pathways,
3) Developing and characterising a rat fibrotic lung model, and
4) Determining whether current CFTR modulator therapies or potential lentiviral gene therapies can fully correct these altered signalling pathways.
These projects will utilise a range of skills including RNAseq analysis, qPCR, Western blotting, cell culture, and immunohistochemistry. These projects may also involve mass spectrometry for lipid analysis and the use of a novel In Vivo Oxidative Status (IVOS) probe to measure oxidative stress levels in the CF rats.
Co-supervisor(s): A. Prof Martin Donnelley, Dr Alexandra McCarron, A. Prof Erik Noschka (Project dependent)
Projects available for: Honours and Masters
Location: Women's and Children's Hospital
Research project start: Semester 1 or 2
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Appointments
Date Position Institution name 2022 - ongoing Postdoctoral researcher University of Adelaide 2021 - 2022 Postdoctoral researcher SA Pathology 2018 - 2020 Postdoctoral researcher University of Adelaide 2015 - 2018 Research Assistant University of Adelaide -
Education
Date Institution name Country Title 2011 - 2015 University of Adelaide Australia PhD 2010 - 2010 Flinders University Australia BSc (Honours) 2007 - 2009 Flinders Univerity Australia Bachelor of Science -
Research Interests
Animal Cell and Molecular Biology Animal Growth and Development Animal Physiology - Cell Biochemistry & Molecular Biology Biochemistry and Cell Biology Biological Biological Sciences Bone and Bones Cell Biology Cell Development, Proliferation and Death Gene and Molecular Therapy Gene Expression Genetics Medical and Health Sciences Respiratory Diseases Respiratory System
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Journals
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Conference Papers
Year Citation 2015 Byers, S., Pout-Pitt, N., Linard, H., Ainslie, L. K., & Roberts, S. A. D. (2015). MPS GAG modulate mesenchymal stem cell differentiation. In MOLECULAR GENETICS AND METABOLISM Vol. 114 (pp. S27-S28). Orlando, FL: ACADEMIC PRESS INC ELSEVIER SCIENCE.
DOI -
Conference Items
Year Citation 2023 Rout-Pitt, N., Mc Carron, A., Boog, B., Parsons, D., & Donnelley, M. (2023). A twist in the cystic fibrosis story—TGF-β1 treatment affects epithelialmesenchymal transition differentially in two cystic fibrosis rat airway cell models. Poster session presented at the meeting of North American Cystic Fibrosis Conference. 2020 Rout-Pitt, N., Delhove, J., Farrow, N., Donnelley, M., & Parsons, D. (2020). Development of an Epithelial Mesenchymal Transition Tracing Vector. Poster session presented at the meeting of MOLECULAR THERAPY. ELECTR NETWORK: CELL PRESS. 2020 Carpentieri, C., Farrow, N., Cmielewski, P., Delhove, J., Rout-Pitt, N., Parsons, D., & Donnelley, M. (2020). Frequency and Timing of Lentiviral Vector Repeat Dose Delivery Does Not Significantly Alter Long-Term Transgene Expression Levels in Mouse Lungs. Poster session presented at the meeting of MOLECULAR THERAPY. ELECTR NETWORK: CELL PRESS. 2019 Rout-Pitt, N., Donnelley, M., & Parsons, D. (2019). OPTIMISATION OF BRONCHOSCOPIC LENTIVIRAL VECTOR DELIVERY FOR DIRECT LOBE TARGETING IN RAT LUNGS. Poster session presented at the meeting of RESPIROLOGY. WILEY. 2018 Byers, S., Rout-Pitt, N., Linard, H., Vaidyanathan, S., & Derrick-Roberts, A. L. K. (2018). MESENCHYMAL STEM CELL DIFFERENTIATION IS MODULATED BY COMPLEX SUGARS IN MPS DISEASE. Poster session presented at the meeting of JOURNAL OF GENE MEDICINE. Univ Technol Sydney, Sydney, AUSTRALIA: WILEY. 2018 McIntyre, C., Rout-Pitt, N., Donnelley, M., & Parsons, D. (2018). LOBE SPECIFIC TARGETING OF LENTIVIRAL VECTOR GENE TRANSFER TO THE LUNGS OF ADULT RATS. Poster session presented at the meeting of PEDIATRIC PULMONOLOGY. WILEY. 2018 McIntyre, C., Cmielewski, P., Craig, F., Rout-Pitt, N., Parsons, D., & Donnelley, M. (2018). CF-RELATED PATHOLOGIES ARE MORE SEVERE IN KNOCKOUT RATS COMPARED TO PHE508DEL RATS. Poster session presented at the meeting of PEDIATRIC PULMONOLOGY. WILEY. 2018 Carpentieri, C., Farrow, N., Cmielewski, P., McIntyre, C., McCarron, A., Rout-Pitt, N., . . . Donnelley, M. (2018). Airway Gene-Addition Therapy for Cystic Fibrosis: the VSV-G Pseudotype Produces Higher Transduction Levels Than HA. Poster session presented at the meeting of MOLECULAR THERAPY. Chicago, IL: CELL PRESS. 2018 Farrow, N., Cmielewski, P., Donnelley, M., Rout-Pitt, N., Bertoncello, I., & Parsons, D. (2018). Epithelial Disruption Enables Human Airway Stem Cell Transplantation in Mouse Nasal Airways. Poster session presented at the meeting of MOLECULAR THERAPY. Chicago, IL: CELL PRESS. 2018 Carpentieri, C., Farrow, N., Mcintyre, C., Cmielewski, P., Rout-Pitt, N., Parsons, D., & Donnelley, M. (2018). COMPARATIVE EFFICIENCY OF HA AND VSV-G PSEUDOTYPED LENTIVIRAL VECTORS FOR CYSTIC FIBROSIS AIRWAY GENE THERAPY. Poster session presented at the meeting of RESPIROLOGY. WILEY. 2017 Farrow, N., Donnelley, M., McIntyre, C., Rout-Pitt, N., & Parsons, D. (2017). Developing high efficiency gene transfer techniques using human air liquid interface cultures. Poster session presented at the meeting of TSANZ Poster presentations, as published in Respirology. Canberra: Wiley. 2017 McCarron, A., Rout-Pitt, N., McIntyre, C., Donnelley, M., & Parsons, D. W. D. (2017). Lentivirus Production in Stirred-Tank and Packed-Bed Basket Bioreactor Systems: A Comparison. Poster session presented at the meeting of MOLECULAR THERAPY. Washington, DC: CELL PRESS. 2017 Farrow, N., Donnelley, M., Rout-Pitt, N., McIntyre, C., Bertoncello, I., & Parsons, D. W. D. (2017). High Efficiency <i>In Vitro</i> Transduction of Human Airway Basal Cells. Poster session presented at the meeting of MOLECULAR THERAPY. Washington, DC: CELL PRESS. 2017 Carpentieri, C. L., Farrow, N., McIntyre, C., McCarron, A., Rout-Pitt, N., Parsons, D., & Donnelley, M. (2017). COMPARATIVE EFFICIENCY OF HA AND VSV-G PSEUDOTYPED LENTIVIRAL VECTORS DEVELOPED FOR TREATING CYSTIC FIBROSIS LUNG DISEASE. Poster session presented at the meeting of PEDIATRIC PULMONOLOGY. WILEY.
2024 N. Rout-Pitt, A. McCarron, D. Parsons, M. Donnelley, Fall Path to a cure (PTAC) Pilot and Feasibility Award Program of the Cystic Fibrosis Foundation (CFF): 'Unravelling the Role of Epithelial-Mesenchymal Transition (EMT) in Cystic Fibrosis Lung Disease: Insights, Challenges, and Therapeutic Prospects', $175,000
2019 N. Rout-Pitt, N. Farrow, J. Delhove, D. Parsons, M. Donnelley, WCH Foundation Grant: “Cell plasticity of the airways: Understanding the stem cell niche to optimise gene therapy and stem cell targeting”, $75,000
2018 N. Rout-Pitt, Cure 4 Cystic Fibrosis Foundation Grant: "Lentiviral vector production facility management", $41,828
2017 M. Donnelley, C. McIntyre, N. Rout-Pitt, A. McCarron, D. Parsons, Channel 7 Children's Research Foundation Grant: “Improving the efficiency of cystic fibrosis airway gene therapy”, $74,213
I am passionate about science and have over ten years research experience as a molecular biologist in bone and respiratory diseases in multi-disciplinary teams delivering high quality research.
I have supervised 3rd year placement, honours, masters and PhD students. My first student in the Masters of Biotechnology program within the School of Biological Sciences provided with a glowing thank you in her thesis.
'...I would like to thank my other supervisor, Dr Nathan Rout-Pitt. Thank you for your careful guidance to my every experiment and giving me the most detailed opinions in the process of my writing. I think he is the most responsible and patient supervisor I have seen in Australia in the past two years. Even in my 18 years of school, I haven't met such a good supervisor as him'
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Current Higher Degree by Research Supervision (University of Adelaide)
Date Role Research Topic Program Degree Type Student Load Student Name 2024 Co-Supervisor Developing an effective airway stem cell therapy for the treatment of Cystic Fibrosis lung disease Doctor of Philosophy Doctorate Full Time Ms Stuti Saini 2023 Co-Supervisor Understanding and improving gene vector targeting with lentiviral magnetic nanoparticles Doctor of Philosophy under a Jointly-awarded Degree Agreement with Doctorate Part Time Ms Madison Michelle Davis
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Committee Memberships
Date Role Committee Institution Country 2024 - ongoing Member IBC committee University of Adelaide Australia 2017 - 2020 Representative EMCR council Robinson Research Institute Australia -
Memberships
Date Role Membership Country 2022 - ongoing Member The EMT International Association Australia 2020 - 2021 Member American Society of Gene and Cell Therapy United States 2019 - 2020 Member Australian and New Zealand Society of Respiratory Science Australia
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