Robert Newton

As a member of the Lung Health  Research Group (formerly the Airways Inflammation Research Group), and a part of the Snyder for Chronic Diseases, my core research interests are on the actions of drugs that are commonly used to treat asthma, chronic obstructive pulmonary disease (COPD) and other inflammatory conditions. In asthma, glucocorticoids (clinically referred to as corticosteroids) are used to treat inflammation, whereas beta2-adrenoceptor agonists can be taken to combat bronchoconstriction during asthma attacks. However, mechanisms by which glucocorticoids exert their anti-inflammatory effects remain incompletely understood, while in severe asthma, COPD and exacerbations of each, glucocorticoids show reduced clinical efficacy. This reduced efficacy requires mechanistic explanation and combined with an incomplete understanding of their anti-inflammatory mechanisms makes it hard to rationally improve glucocorticoid effectiveness. We therefore seek understand the effects of glucocorticoids on signalling and gene expression to better understand the anti-inflammatory actions of these clinically important drugs.

In the control of asthma, and COPD, clinical evidence suggests that use of combination inhalers containing both a glucocorticoid and a long-acting beta2-adrenoceptor agonist (LABAs) improve the efficacy of the glucocorticoid. This enhanced effect is also poorly understood, but could assist in designing improved combination therapies. We, in collaboration with Prof. Mark Giembycz, are examining the molecular basis for the enhancement of glucocorticoid action by LABAs.

Main projects:

A. Mechanisms of anti-inflammatory glucocorticoid action

Acting on the glucocorticoid receptor (GR), glucocorticoid induce the expression of many hundreds of genes. Glucocorticoids also reduce the expression of very many inflammatory genes and this effect is largely responsible for their clinical efficacy in diseases suck as asthma. We explore the effects of glucocorticoids on gene expression and seek to understand how glucocorticoids act to reduce inflammatory signalling and gene expression. 

B. Enhancement of glucocorticoid action by long-acting beta2-adrenoceptor agonists (LABAs)

Combination inhalers that contain both a glucocorticoid and a long-acting beta2-adrenoceptor agonist (LABAs) improve the control of asthma more than can be achieved by merely increasing the dose of glucocorticoid. We previously showed that LABAs are able to enhance many of the gene expression events that are induced by glucocorticoids. As this effect may unpin the clinical effectiveness of glucocorticoid/LABAs combination therapies, we are seeking to characterise and understand the molecular interactions that occur between these two classes of drug.

C. Inflammatory signal transduction and gene expression

To understand how glucocorticoids operate to reduce inflammatory gene expression requires that we more fully understand the processes that lead to the expression of inflammatory genes. Thus, core inflammatory cytokines, including interleukin-1β (IL1B), tumor necrosis factor-α (TNF) and toll-like receptors (TLRs) induce signalling cascades that activate transcription factors such as nuclear factor κB (NF-κB) and activator protein 1 (AP-1). These then lead to the expression of numerous cytokines, chemokines and other inflammatory genes. While many of the pathways that lead to inflammatory gene expression are well-characterised, others are poorly understood. We aim to characterise signalling and gene expression downstream of key pro-inflammatory receptors in order to better understand the effects of glucocorticoids.

Funding 

Selected current & recent funding

2022 – 2027 Understanding glucocorticoid resistance in inflammatory disease. CIHR.

2018 – 2023 Molecular mechanisms underlying the enhanced efficacy of inhaled corticosteroid/long-acting β2-adrenoceptor agonist combinations used in asthma. CIHR.

2016 – 2022 Characterisation and elucidation of gene expression programmes downstream of the activated glucocorticoid receptor. NSERC discovery.

Trainees / Training

Mahmoud Mostafa (PDF)
Email: mahmoud.mostafa@ucalgary.ca

Andrew Thorne (PhD Student)
Email: andrew.thorne@ucalgary.ca

Daniela Urrego (PhD Student, Co-Supervisor, supervised by Dr. Donna Slater) 
Email: durrego@ucalgary.ca

Amandah Necker-Brown (PhD student)
Email: amandah.neckerbrown@ucalgary.ca

Priyanka Chandramohan (Master/PhD Student)
Email: priyanka.chandramoha@ucalgary.ca

Keerthana Kalyanaraman (Master/PhD Student)
Email: keerthana.kalyanaram@ucalgary.ca

Undergraduate training & supervision – The lab will typically take on 1 or 2 summer students plus will supervise 1 or 2 Hons projects (BHSc 508, CMMB 530, etc) each year. Interested individuals should familiarise themselves with the work of our lab and apply directly to Dr. Newton. Final year project students are strongly recommended to undertake prior summer work in the lab.

Statement on equity, diversity and inclusion: Consistent with University policy and the statements made on the Department of Physiology and Pharmacology website, the Newton lab welcomes individuals from all backgrounds. To this end, I would like to specifically encourage individuals from equity deserving groups to apply for training positions in my lab.

I firmly believe that a diverse, inclusive and fair workplace provides an optimal scientific environment. I try to maintain a culturally balanced group where race, gender and/or other labels do not factor against success. Our community is represented by multiple nationalities, ethnicities and cultures. While being an emigrant to Canada, I also recognise considerable privilege in my upbringing and education. By working together, we can make a difference.