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Publications of the Week

FAM13A as Potential Therapeutic Target in Modulating TGF-Beta-Induced Airway Tissue Remodelling in COPD

By July 6, 2021No Comments

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This week we profile a recent publication in the American Journal of Physiology – Lung Cellular and Molecular Physiology from Dr. James Lim’s (pictured, left) lab at the BC Children’s Hospital Research Institute and Dr. Don Sin’s lab at the Centre for Heart and Lung Research, with lead author Dr. Anthony Tam (right). 

Can you provide a brief overview of your lab’s current research focus?

The Lim laboratory at BC Children’s Hospital Research Institute (BCCHR) investigates the molecular mechanisms governing cell adhesion and motility, and how these physiological processes can mediate tumour behaviour including drug resistance, survival/proliferation and cell death, and tumour immunogenicity. A key technology employed in the laboratory include using CRISPR-mediated gene editing to generate loss of function cell lines and for assessing the roles of mutations with yet unknown functions.  

The Sin laboratory (co-communicating author) at Centre for Heart Lung Innovation, St. Paul’s Hospital, has research interests in understanding inflammatory lung condition in cardiovascular diseases and identifying biomarkers and elucidating their function for Chronic Obstructive Pulmonary Disease (COPD).

What is the significance of the findings in this publication?

The research paper, published in the American Journal of Physiology – Lung Cellular and Molecular Physiology, explores the role of FAM13A, one of several promising candidate genes identified from genome wide association studies (GWAS) in patients with COPD discovered in Dr. Don Sin’s laboratory. To understand the biology of this gene, we used CRISPR-Cas9 to generate airway epithelial cells deficient in FAM13A and screened for biological readouts that are relevant for COPD. In collaboration with Dr. Pieter Cullis, we also employed gain of function approaches to overexpress FAM13A in airway epithelial cells. This was achieved using lipid nanoparticle technology to encapsulate and deliver FAM13A mRNA, the same technology used in Pfizer-BioNTech mRNA vaccines. We found that FAM13A may be protective against a COPD-related fibrotic response in the airway epithelium, pointing toward a potential therapy in controlling the extend of fibrosis and respiratory symptoms among smokers at risk for COPD and those with mild COPD.

What are the next steps for this research?

According to the WHO, COPD is the third leading cause of death worldwide, causing 3.23 million deaths in 2019. Combining CRISPR and LNP technologies, we believe we can find novel biology from other GWAS-identified genes to understand their contribution to COPD progression and to determine their potential for therapeutic targeting in controlling other COPD symptoms such as mucous hypersecretion and pathogen-mediated lung exacerbations.

Funding Sources:

Dr. Anthony Tam, lead author, is a recipient of a MITACS Accelerate fellowship award. This study receives support from the Canadian Institute of Health Research (CIHR) and the NanoMedicines Innovation Network (NMIN), a Canadian Networks of Centres of Excellence (NCE) in nanomedicine. Dr James Lim acknowledges support received from the Michael Cuccione Childhood Cancer Research Program at BCCHR.

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