Pulmonary fibrosis is a group of lung disorders in which tissue becomes scarred, making it harder for the lungs to transfer oxygen into the bloodstream. Idiopathic pulmonary fibrosis (IPF), one form of the disease, can progress at different rates among patients. Some experience a gradual decline in lung function, while others deteriorate more quickly despite treatment. This variation has led researchers to investigate biomarkers, measurable biological features that may help explain disease activity, predict outcomes, or identify differences between patients. Blood proteins, small RNA molecules and changes in cellular activity are among the signals being studied. Their clinical value depends on whether research findings can be confirmed across patient groups and used reliably in medical care.
Yuben Moodley, a respiratory physician and researcher at the University of Western Australia (UWA), has worked on several parts of this field, from the molecular behavior of lung cells to blood-based indicators of disease progression. His research has included extracellular vesicles, microRNAs, gene-expression patterns, and biomarkers associated with outcomes in people receiving antifibrotic treatment. These projects involve collaborations through the Australian Idiopathic Pulmonary Fibrosis Registry and international research groups. Together, they examine whether biological measurements can help explain why patients with the same diagnosis may follow different clinical courses.
An early part of Moodley’s research examined how fibroblasts respond to inflammatory signals; in a 2003 study published in The American Journal of Pathology, Moodley and colleagues compared lung fibroblasts from healthy tissue with those from patients with IPF. They found differences in signaling through interleukin-6 (IL-6) and gp130, a component of the receptor system involved in the response. In normal fibroblasts, sustained STAT3 activation inhibited cell proliferation. In fibroblasts from IPF lungs, the response involved the mitogen-activated protein kinase (MAPK) pathway and increased proliferation. The study provided evidence that cells in fibrotic lungs can respond differently to the same signaling molecule.
This work focused on activity inside lung tissue, but later research also examined whether changes associated with fibrosis could be detected in blood. Circulating biomarkers may offer a less invasive way to study disease activity over time. However, a marker associated with progression does not necessarily cause it. Moodley’s research program has included circulating proteins, RNA molecules carried in small extracellular vesicles, and gene-expression patterns in lung cells. His UWA research profile also lists work on circulating monocytes, epigenetic changes, and spatial transcriptomics, which examines gene activity in the context of tissue structure.
In 2019, Moodley was among the authors of a technical paper in the Journal of Immunological Methods describing a standardized protocol for evaluating small extracellular vesicles in plasma. These tiny particles are released by cells and carry biological material, including proteins and RNA. Researchers study them because their contents may reflect changes in the cells from which they originate. The team used imaging flow cytometry, a method that combines imaging with flow-based analysis, to characterize and quantify individual particles. The protocol addressed technical difficulties in detecting small vesicles and distinguishing them from other material in plasma. Consistent measurement is important when comparing results between laboratories or patient groups.
A larger collaborative study published in the European Respiratory Journal in 2022 examined biomarker signatures associated with progressive IPF. Led by Britt Clynick and involving Moodley and researchers from several institutions, the study assessed patient data from three independent groups: the Australian Idiopathic Pulmonary Fibrosis Registry, the Trent Lung Fibrosis cohort and the PROFILE study. Researchers measured candidate proteins and used a broader proteomic approach to investigate which biological signals were associated with disease progression. The use of separate cohorts allowed the researchers to test whether findings extended beyond a single patient group. The study formed part of efforts to develop biomarkers that could support prognosis and improve understanding of differences in disease course.
The research also sits within a wider effort to link biomarker findings with patient outcomes and clinical trials. The Australian registry provides clinical information and blood samples for studies of disease progression, while other cohorts allow findings to be tested in different settings. Moodley’s research profile reports work identifying circulating RNA associated with lung cancer in patients with progressive IPF. This line of research addresses the observed relationship between pulmonary fibrosis and lung cancer.
In July 2024, a multicenter study led by Hernan Fainberg, with Moodley among its co-authors, examined whether blood biomarkers could identify distinct molecular patterns in pulmonary fibrosis. Published in The Lancet Respiratory Medicine, the study used 13 biomarkers linked to extracellular matrix remodeling, epithelial stress, and blood clotting. Researchers first analyzed participants in the UK PROFILE study, which included people with newly diagnosed IPF or nonspecific interstitial pneumonia, then assessed the findings in an independent group. The aim was to classify patients by biological patterns, often called endotypes, rather than relying only on their clinical diagnosis. The study offered a way to investigate why patients with fibrotic lung disease may have different outcomes.
The importance of this approach lies in the possibility that patients grouped under the same disease label may have different underlying biological processes. If these patterns can be confirmed and linked to outcomes, they may eventually help researchers design more focused clinical trials or identify patients who need closer monitoring. However, biomarker clustering is a research method, not an established replacement for clinical assessment. The 2024 study contributed evidence for biological variation within pulmonary fibrosis, while leaving further work to establish how the classifications might guide treatment decisions.
A 2025 study published in Respirology examined matrix metalloproteinase-7 (MMP7), a protein involved in tissue remodeling, in 98 people with IPF receiving antifibrotic treatment. The researchers measured blood levels at four time points over one year. Patients were classified as having progressive disease if their forced vital capacity fell by at least 10%, their diffusing capacity fell by at least 15%, or they died within a year of starting treatment. Higher baseline MMP7 levels were associated with progression in both study cohorts. In the combined analysis, elevated levels were also associated with increased mortality risk. The authors reported that a panel combining MMP7 with other biomarkers improved the assessment of progression and mortality risk.
Another study, published in the American Journal of Respiratory and Critical Care Medicine in December 2025, investigated let-7f-5p, a microRNA carried in circulating small extracellular vesicles. Researchers compared samples from patients with progressive and stable IPF in Australian and US cohorts. Lower levels of let-7f-5p were associated with progressive disease, while experimental work indicated that the molecule had antifibrotic effects in laboratory models. The findings raised the possibility that this microRNA could be relevant to both disease monitoring and future therapeutic research. However, the study did not establish a validated diagnostic test or demonstrate that administering let-7f-5p would treat IPF in patients.
Moodley’s current research interests at UWA include epigenetic and transcriptomic profiling of lung cells, spatial transcriptomics of early lung injury and fibrosis, and the analysis of microRNAs in circulating extracellular vesicles. Epigenetic research examines changes that affect gene activity without altering the underlying DNA sequence, while transcriptomic analysis studies which genes are active in cells. Spatial methods add information about where those activities occur within tissue. These approaches may help researchers connect blood-based signals with processes taking place inside the lung. Yuben Moodley’s work across these areas continues to examine how molecular measurements can clarify differences in pulmonary fibrosis, while the clinical usefulness of individual biomarkers remains dependent on further testing and independent validation.
Disclaimer: This article is for informational and educational purposes only and should not be considered professional medical advice. The information presented is based on available research and may be subject to change as new findings emerge. Readers are encouraged to consult a qualified healthcare professional for advice regarding their individual health concerns.
