Understanding and targeting molecular mechanisms of respiratory diseases

Wadhwa, Ridhima

Understanding and targeting molecular mechanisms of respiratory diseases

Wadhwa, Ridhima

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Publication Type:: Thesis
Issue Date:: 2022

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Field	Value	Language
dc.contributor.author	Wadhwa, Ridhima
dc.date.accessioned	2024-04-11T04:03:41Z
dc.date.available	2024-04-11T04:03:41Z
dc.date.issued	2022
dc.identifier.uri	http://hdl.handle.net/10453/177726
dc.description	University of Technology Sydney. Graduate School of Health.	en_US.UTF-8
dc.description.abstract	Metabolic homeostasis in immune cells is essential for mediating key physiological and pathological processes, including cell proliferation, differentiation, inflammation, and death. The investigations described in this thesis provide strong evidence that mitochondrial dysfunction, oxidative stress, and altered metabolism play essential roles in the pathogenesis of the chronic respiratory diseases, chronic obstructive pulmonary disease (COPD) and severe asthma. Mitochondrial dysfunction drives inflammation that is a hallmark feature of chronic respiratory diseases. The use of metabolic modulators specifically target mitochondria and limit inflammation. In addition, treatment with metabolic modulators provides a better understanding of changes in macrophage polarisation, mitochondrial dysfunction, metabolic changes, and oxidative stress in chronic respiratory diseases. Using representative mouse models, we have shown for the first time that increased glycolysis may play a crucial role in driving the pathogenesis of chronic respiratory diseases while increased oxidative phosphorylation may promote anti-inflammatory effects. Thus, mitochondrial dysfunction, mitochondrial reactive oxygen species (mtROS) and altered metabolism are important in driving inflammation. Our findings emphasise that specific inhibitors of ROS and metabolic modulators could be translated into novel treatment strategies to mitigate the highlighted chronic respiratory diseases in the respiratory clinic.	en_US.UTF-8
dc.format	Thesis (PhD)
dc.language.iso	en_US	en_US.UTF-8
dc.relation	https://opus.lib.uts.edu.au/bitstream/10453/177726/2/02whole.pdf
dc.rights	info:eu-repo/semantics/embargoedAccess
dc.rights	The author owns the copyright in this thesis including all reproduction and reuse rights for the work. The work may not be altered without the permission of the copyright owner. Attribution is essential when quoting or paraphrasing from this thesis.
dc.rights	© 2022 Ridhima Wadhwa
dc.rights	au.edu.uts.lib/cph
dc.title	Understanding and targeting molecular mechanisms of respiratory diseases	en_US.UTF-8
dc.type	Thesis
utslib.copyright.status	embargoed	*
utslib.copyright.embargo	2026-02-08T00:00:00+1000

Abstract:

Metabolic homeostasis in immune cells is essential for mediating key physiological and pathological processes, including cell proliferation, differentiation, inflammation, and death. The investigations described in this thesis provide strong evidence that mitochondrial dysfunction, oxidative stress, and altered metabolism play essential roles in the pathogenesis of the chronic respiratory diseases, chronic obstructive pulmonary disease (COPD) and severe asthma. Mitochondrial dysfunction drives inflammation that is a hallmark feature of chronic respiratory diseases. The use of metabolic modulators specifically target mitochondria and limit inflammation. In addition, treatment with metabolic modulators provides a better understanding of changes in macrophage polarisation, mitochondrial dysfunction, metabolic changes, and oxidative stress in chronic respiratory diseases. Using representative mouse models, we have shown for the first time that increased glycolysis may play a crucial role in driving the pathogenesis of chronic respiratory diseases while increased oxidative phosphorylation may promote anti-inflammatory effects. Thus, mitochondrial dysfunction, mitochondrial reactive oxygen species (mtROS) and altered metabolism are important in driving inflammation. Our findings emphasise that specific inhibitors of ROS and metabolic modulators could be translated into novel treatment strategies to mitigate the highlighted chronic respiratory diseases in the respiratory clinic.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/177726