Pawan Sharma

Woolcock Institute of Medical Research

What are some of the key findings, progress and discoveries you have made with your research to date – and how will this make a difference to patients with this disease?

My research focuses on discovering and identifying novel mechanisms that can become effective, and safe drug targets for Chronic Obstructive Pulmonary Disease (COPD). Following this direction, my research identified apoptosis regulating signal kinase 1 (ASK1) as one of the targets for COPD. In patients with severe disease and remodelled airways (with small airway fibrosis and increased airway smooth muscle mass) we found greater expression of ASK1 in the airway mesenchymal cells of these patients. We know that increased ASM mass is one of the key drivers of airway remodelling in COPD. Current therapies provide only symptomatic relief and fail to halt disease progression. Our research showed that ASK1 inhibition reduced mitogen-induced ASM cell growth and migration that contributes to airway remodelling in COPD. These findings have greater implication – as no current medications effectively reverse structural changes in COPD. We believe the avenue of ASK1 inhibition is an attractive therapeutic target. This work is now published in Clinical Science (2018) 132 1615–1627.

What do you hope to achieve with this research project?

With this work we want to identify new chemical inhibitors that are safe but highly selective in targeting ASK1 in COPD patients. We would like to take these novel molecules to preclinical research using a smoke-induced COPD model in mice to test their efficacy in a disease setting. Ultimately, we aim to develop a molecule that can be given directly into the lungs (inhalation) to avoid systemic toxicity, and off-target effects in COPD patients.

How important was the funding from Lung Foundation Australia to your work?

Lung Foundation Australia’s funding was important as it enabled me to present this work at an international forum. I met many researchers at this forum who became interested in this work and we were able to collaborate and work together. We have now published together in this area, and hope to continue to work together and apply for joint grant applications in the future.

Do you have a message for Lung Foundation Australia’s supporters?

Chronic respiratory diseases such as asthma and COPD do not get enough support from the general public and donors as compared to cancer and cardiovascular diseases in Australia. I really appreciate the hard work of Lung Foundation Australia’s supporters in raising money so that researchers like me can keep working to discover new drugs for chronic respiratory diseases.