Extracellular Granzyme K as a Novel Driver of Psoriasis: Mechanistic Insights and Development of Topical Therapeutics
Principal Investigator: David J. Granville, Ph.D.
Institution: University of British Columbia
Grant Mechanism: Translational Research Grant
Funding Amount: $200,000
Project Start Date: August 1, 2025
Project End Date: July 31, 2027
Status: Active
Keywords:
Project Summary:
Psoriasis is a chronic skin condition that causes painful, scaly patches and affects millions worldwide. This project investigates a protein called Granzyme K, which worsens psoriasis. Granzyme K is released in skin by immune cells and works like molecular scissors. By cutting other proteins, Granzyme K modifies their function causing wide-spread ripple effects on different cell types, promoting skin cell replication and increasing skin inflammation. We aim to identify the proteins cut by Granzyme K and how that contributes to psoriasis, to develop tools to track Granzyme K activity, and to create new drugs to block its harmful effects. By targeting this protein, we hope to develop affordable and effective treatments, improving the lives of those living with psoriasis.
How will your project help improve the lives of the 125 million affected by psoriatic disease?
This project directly supports the NPF mission to cure psoriatic disease and improve the lives of those affected by uncovering a novel therapeutic target, granzyme K (GzmK), implicated in psoriasis. By identifying GzmK substrates, developing activity probes, and designing specific inhibitors, our research aims to deliver innovative, cost-effective treatments that address the limitations of current therapies. Through this work, we strive to advance understanding of psoriasis pathogenesis, provide new therapeutic options, and ultimately reduce the burden of disease for millions living with psoriasis worldwide.
Why is psoriatic disease research important to you, personally? What role will this award play in your research efforts or career development?
Psoriatic disease is prevalent in our communities and afflicts diverse populations irrespective of sex, age, or race. Psoriasis can be a debilitating disease with physical, emotional, and psychosocial impact, and there is a clinical need for novel solutions. From a personal perspective, while I do not exhibit any symptoms of psoriasis, my father was impacted and my sister’s daughter is significantly affected by psoriasis. As a young adult who recently graduated, I have witnessed how this condition has affected her personally and socially. As such, I am motivated to develop better treatment options. This award will enable the expansion of our team and increased research efforts dedicated to delineating the mechanisms of Granzyme K in psoriasis and importantly to develop a first-in-class therapeutic against Granzyme K. The arrival of this funding is timely as current interest in Granzyme K in the field is unprecedented, resulting in an upsurge of data and insights related to Granzyme K, and our team has recently developed and optimized a novel and unique methodology pipeline for the degradomic analyses of granzymes. We anticipate that we will be able to leverage findings arising from this project to obtain additional funding for the advancement of a novel Granzyme K inhibitor into the clinic.
Researcher Profile:
Dr. David Granville is a Professor in the Department of Pathology and Laboratory Medicine, Faculty of Medicine, at the University of British Columbia (UBC) in Vancouver, BC, Canada. He is also the Director of the BC Professional Firefighters’ Burn and Wound Healing Laboratory and a Principal Investigator at the International Collaboration On Repair Discoveries (ICORD) Centre and the UBC Centre for Heart Lung Innovation. Dr. Granville is the former Executive Director of the Vancouver Coastal Health Research Institute (VCHRI) and Associate Dean, Research, Faculty of Medicine, UBC. His research is focused on understanding the mechanisms underlying tissue injury, inflammation and repair, and identifying therapeutic targets and approaches that attenuate premature aging and/or chronic inflammatory disease. His previous research has contributed to the development of verteporfin (Visudyne®) as the first FDA approved treatment for age-related macular degeneration. More recently, much of his research has been devoted towards granzyme serine proteases and their role(s) in chronic, autoimmune, and/or age-related inflammatory diseases.