Nathan Rout-Pitt

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.

Lung fibrosis in cystic fibrosis (CF) remains poorly defined, with few studies exploring its development or underlying cellular mechanisms over the past 10–15 years. My research explores the premise that this process of fibrosis is hindering the effectiveness of clinically approved therapies (e.g. modulators) and those under development (e.g. gene therapy). At the University of Adelaide Cystic Fibrosis Airway Research Group, our goal is to cure CF airway disease through CFTR gene-addition therapy. Gene therapy efforts have often prioritized speed to clinic over understanding CF’s biological complexity, meaning that there are still no gene therapies on the market for CF. While CFTR modulator drugs like Trikafta have improved care for many, they are ineffective for about 30% of patients due to ineligible mutations, side effects, or limited benefit. My research goal is to ‘Cure CF through a deeper understanding of its biological complexity’, including assessing signalling pathways that drive fibrosis.

The main focuses of my current research include:
- Modeling CF lung disease in rats.
- Identifying fibrosis-related pathways in CF.
- Linking these fibrosis related pathways to CFTR trafficking.
- Evaluating the Reversibility of fibrotic signaling pathways.

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

 

 

2025 N. Rout-Pitt, Robinson Research Institute Step Funding, "Characterising basal epithelial stem cell subpopulations in cystic fibrosis airways: Investigating the inherent risk of fibrosis", $40,000

2025 N. Rout-Pitt, A, McCarron, M, Donnelley, Cystic Fibrosis Australia Conquer Cystic Fibrosis Gene Therapies Innovation grant, "Improving CFTR gene therapy by ensuring airway cells exist in an epithelial state", $80,000 

2024 N. Rout-Pitt, Robinson Research Institute Step Funding, "Assessing how lipid metabolism changes in Cystic Fibrosis epithelial cells during Epithelial Mesenchymal Transition", $15,000

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'

  • Position: Grant funded researcher (B)
  • Phone: 81619179
  • Email: nathan.rout-pitt@adelaide.edu.au
  • Campus: Womens & Childrens Hospital
  • Building: WCH - Gilbert Building, floor 6
  • Org Unit: Women's and Children's Health
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