Dr.
Granville, David
PhD, FAHA
Academic Ranks(s):
Professor and Associate Dean Research, Faculty of Medicine, University of British Columbia, Executive Director, Vancouver Coastal Health Research Institute (VCHRI), Director, BC Professional Firefighters’ Burn and Wound Healing Research Group, VCHRI, Principal Investigator, ICORD Centre, Principal Investigator, UBC Centre for Heart Lung Innovation, Founder and CSO, viDA Therapeutics
Affiliations(s):
Affiliations with Organizations:
- BC Professional Firefighters’ Burn and Wound Healing Research Laboratory
- Centre for Drug Research and Development UBC Centre for Heart Lung
- Innovation UBC Department of Pathology UBC Department of Surgery
- viDA Therapeutics, Inc
Dr. David Granville is a Professor and Associate Dean of Research in the Faculty of Medicine and the Executive Director of Vancouver Coastal Health Research Institute (VCHRI; www.vchri.ca), Canada’s 5th largest hospital-based research institute. Dr. Granville is a principal investigator at ICORD Centre, the UBC Centre for Heart Lung Innovation, and is the Director of the BC Professional Firefighters’ Wound Healing and Regeneration Research Group, VCHRI. His research program focuses on aging and chronic inflammation and the discovery of novel therapeutics for age-related and chronic inflammatory conditions. In his early career, he worked at QLT, Inc. (1994-2001) where his R&D studies supported the approval of Visudyne® to be used as the first treatment for macular degeneration, the leading cause of blindness in the elderly. In 1999 Visudyne® was approved by the FDA resulting in the largest ophthalmic product release in history. Dr. Granville’s research is referred to on the drug label for Visudyne®. In 2001, Dr. Granville relocated to the Scripps Research Institute in California where his research identified a novel therapeutic approach for reducing myocardial infarction. Dr. Granville is a primary inventor on several publications and patents pertaining to the latter discoveries that led to the formation of Radical Therapeutix Inc. (San Diego, CA). In 2003, Dr. Granville was recruited to UBC as a Canada Research Chair and Michael Smith Foundation for Health Research scholar. Dr. Granville has received many prestigious awards including: Canada Top 40 Under 40™ award, UBC Outstanding Young Alumnus Award, SFU Academic Alumnus Award, Canadian Association of Pathologists Junior Scientist Award, Business in Vancouver Top Forty Under 40 Award and was a runner-up for the prestigious Louis and Arnold Katz Basic Science Prize at the American Heart Association Scientific Sessions. In 2014, he was named as a Fellow of the American Heart Association (FAHA) and in 2019 he was also inducted as a Scholar of the Royal Society of Canada. Since arriving at UBC, his translational research program (www.granzymes.com) has continued to focus on tissue injury, inflammation and repair resulting in numerous publications and patents, leading to the formation of a local biotechnology spinoff company (viDA Therapeutics).
Academic Background
- PDF, The Scripps Research Institute, Molecular and Experimental Medicine. 2003
- PhD, The University of British Columbia, Pathology and Laboratory Medicine. 2001
- BSc, Simon Fraser University, Biological Sciences. 1994
Awards and Recognition
Awards
- Scholar of the College of New Scholars, Artists and Scientists of the Royal Society of Canada. Royal Society of Canada. Inducted November 21, 2014.
- Fellow of the American Heart Association (FAHA). Inducted May 13, 2014
- 2013 International Academy of Cardiovascular Sciences Symposia Award Runner-Up. One of 5 speakers Selected and Invited to speak in Eric Olson Oration. August, 2013
- 2009 BIV Forty Under 40 Award, Business in Vancouver, Vancouver, BC, January 28, 2010
- Canadian Association of Pathologists Junior Scientist Award, Canadian Association of Pathologists, Ottawa, ON, Jul 14, 2008
- 2007 Outstanding Alumni Award for Academic Achievement, Simon Fraser University, February, 2008
- American Heart Association Scientific Sessions Finalist – Louis N and Arnold M Katz Basic Science Research Prize. 2007.
- Outstanding Young Alumnus Award, University of British Columbia, November 2, 2006.
- Young Investigator Merit Award, American Heart Association Council on Arteriosclerosis, Thrombosis, and Vascular Biology, ($500), November 2006
- Wilbert J. Keon Award for Basic Science, CIHR Institute of Circulatory and Respiratory Health Young Investigator Forum, Finalist ($1500), May 2006
- “Wall of Fame” Inductee, Terry Fox Senior Secondary School, May 31, 2006
- Young Investigator Award, Canadian Stroke Network, ($1500), May 2006
- Canada Top 40 Under 40 Award, Caldwell Partners, May 2005. 40 recipients chosen from ~1500 nominees.
- Wilbert J. Keon Award for Basic Science, CIHR Institute of Circulatory and Respiratory Health Young Investigator Forum, Finalist ($1500), Apr 2005
- CIHR III Travel Award, CIHR Institute of Infection and Immunity Young Investigator Forum, Apr 2005
- Young Investigator Award, Canadian Society of Transplantation, ($1500), May 2004
- Michael Smith Foundation for Health Research Scholar, Career investigator award, Michael Smith Foundation for Health Research, 2003-2008
- Tier II Canada Research Chair in Cardiovascular Biochemistry, Career investigator award, Canada Research Chairs/CIHR, 2003-2008
- Outstanding Oral Presentation, The Scripps Research Institute Society of Fellows Fall Research Symposium, Oct 25, 2002
- Post-Doctoral Fellowship, Canada Institutes of Health Research, 2001-2004
- Research Traineeship, Heart and Stroke Foundation of Canada, 1997-2000
Publications
Hiebert PR, Wu D, Granville DJ. Granzyme B degrades extracellular matrix and contributes to delayed wound contraction in Apolipoprotein E knockout mice. Cell Death Differ. 2013 20(10):1404-14.
Marchant D, Bellac C, Moraes TJ, Wadsworth S, Dufour A, Butler GS, Bilawchuk L, Hendry R, Robertson G, Cheung C, Ng J, Ang L, Luo Z, Heilbron K, Norris M, Duan W, Bucyk, Karpov A, Devel L, Georgiadis D, Hegele RG, Luo H, Granville DJ, Dive V, McManus BM, Overall CM. Transcriptional role of moonlighting MMP12 in antiviral immunity. Nature Med. 2014; 20(5):493-502.
Hsu I, Parkinson LG, Shen Y, Toro A, Brown T, Zhao H, Bleackley RC, Granville DJ. Serpina3n Accelerates Tissue Repair in a Diabetic Mouse Model of Delayed Wound Healing. Cell Death Dis. 2014; 5:e1458. doi: 10.1038/cddis.2014.423.
Parkinson LG, Toro A, Brown K, Tebbutt SJ, Granville DJ. Granzyme B mediates both direct and indirect cleavage of extracellular matrix in skin after chronic low-dose ultra-violet light irradiation. Aging Cell. 2015: 14(1): 67-77.
Shen Y, Cheng F, Sharma M, Merkulova Y, Raithatha SA, Parkinson LG, Zhao H, Westendorf K, Bohunek L, Bozin T, Hsu I, Ang LS, Williams SJ, Bleackley RC, Eriksson JE, Seidman MA, McManus BM, Granville DJ. Granzyme B Deficiency Protects against Angiotensin II-Induced Cardiac Fibrosis. Am J Pathol. 2016: 186(1):87-100.
Shen Y, Russo V, Zeglinski MR, Sellers SL, Wu Z, Oram C, Santacruz S, Merkulova Y, Turner C, Tauh K, Zhao H, Bozin T, Bohunek L, Zeng H, Seidman MA, Bleackley RC, McManus BM, Ruoslahti E, Järvinen TAH, Granville DJ. Recombinant Decorin Fusion Protein Attenuates Murine Abdominal Aortic Aneurysm Formation and Rupture. Sci Rep. 2017 7(1):15857. doi: 10.1038/s41598-017-16194-8.
Shen Y, Zeglinski MR, Turner CT, Raithatha SA, Wu Z, Russo V, Oram C, Hiroyasu S, Nabai L, Zhao H, Bozin T, Westendorf K, Kopko I, Huang R, Arns S, Tan S, Zeng H, Boey A, Liggins R, Jaquith J, Cameron DR, Papp A, Granville DJ. Topical Small-molecule Granzyme B Inhibitor Improves Remodeling in A Murine Model of Impaired Burn Wound Healing. Mol. Exp. Med. 2018 50(5):68.
Russo V, Klein T, Lim DJ, Solis N, Machado Y, Hiroyasu S, Nabai L, Shen Y, Zeglinski M, Zhao H, Oram C, Lennox PA, Van Laeken N, Carr NJ, Crawford RI, Franzke CW, Overall CM, Granville DJ. Granzyme B is elevated in autoimmune blistering diseases and cleaves key anchoring proteins of the dermal-epidermal junction. Sci Rep. 2018 7(1):15857. doi: 10.1038/s41598-017-16194-8.
Turner CT, Lim D, Granville DJ. Granzyme B in Skin Inflammation and Disease. Matrix Biol. 2019 75-76:126-140.
Turner CT, Zeglinski MR, Richardson KC, Zhao H, Shen Y, Papp A, Bird PI, Granville DJ. Granzyme K expressed by classically activated macrophages contributes to inflammation and impaired remodeling. J. Invest. Dermatol. 2019: 139(4):930-939.
Cait J, Hughes MR, Zeglinski MR, Chan A, Osterhof S, Canals D, Cait A, Vogl W, Bernatchez P, Granville DJ, Murphy T, Roskelley C, McNagny KM. Podocalyxin is required for appropriate endothelia cell-cell junction fornation and maintenance of blood brain barrier integrity during acute inflammation. 2019 Feb 20. Proc. Natl. Acad Sci USA 2019: 116(10): 4518-4527.
Liu B*, Granville DJ*, Golledge J*, Kassiri Z. Pathogenic mechanisms and the potential of drug therapies for aortic aneurysm. Am. J. Physiol. Heart Circ. Physiol. 2020: 318(3):H652-H670
Matsubara JA, Tian Y, Cui JZ, Zeglinski MR, Hiroyasu S, Turner CT, Granville DJ. Retinal Distribution and Extracellular Activity of Granzyme B: A Serine Protease that Degrades Retinal Pigment Epithelial Tight Junctions and Extracellular Matrix Proteins. Front. Immunol. 2020; 11:574: 1-13. doi: 10.3389/fimmu.2020.00574
Turner CT, Zeglinski MR, Richardson KC, Santacruz S, Hiroyasu S, Wang C, Zhao H, Shen Y, Sehmi R, Lima H, Gauvreau GM, Granville DJ. Granzyme B contributes to barrier dysfunction in oxazolone-induced skin inflammation through E-cadherin and FLG cleavage. J. Invest. Dermatol. 2021: 141(1):36-47
Sellers SL, Hensey M, Cartlidge TRG, Turner CT, Lau K, Lai A, Salcudean H, Sathananthan J, McManus BM, Granville DJ, Payne GW, Pibarot P, Webb JG, Newby DE, Blanke P, Seidman MA, Dweck MR, Leipsic JA. Tricuspid Valve-in-Valve and Bioprosthetic Surgical Tricuspid and Pulmonic Valve Degeneration: Lessons From Imaging and Histopathology. JACC Cardiovasc Imaging. 2020 S1936-878X(20)30498-8.
Hiroyasu S, Zeglinski MR, Zhao H, Pawluk MA, Turner CT, Kasprick A, Tateishi C, Nishie W, Burleigh A, Lennox PA, Van Laeken N, Carr NJ, Peterson F, Crawford RI, Shimizu H, Tsuruta D, Ludwig RJ, Granville DJ. Granzyme B Inhibition Reduces Disease Severity in Autoimmune Blistering Diseases. Nature Comm. 2021 12(1):302. doi: 10.1038/s41467-020-20604-3.
Gapud EJ, Trejo-Zambrano MI, Gomez-Banuelos E, Tiniakou E, Antiochos B, Granville DJ, Andrade, Casciola-Rosen L, Rosen A. Granzyme B induces IRF-3 phosphorylation through a perforin-independent proteolysis-dependent signaling cascade without inducing cell death. J. Immunol. 2021 206(2):335-344. doi: 10.4049/jimmunol.2000546
Turner CT, Bolsoni J, Zeglinski MR, Zhao, H, Ponomarev T, Richardson K, Hiroyasu S, Schmid E, Papp A, Granville DJ. Granzyme B Mediates Impaired Healing of Pressure Injuries in Aged Skin. NPJ Aging Mech Dis. 2021 5;7(1):6. doi: 10.1038/s41514-021-00059-6
Jung K, Pawluk MA, Lane M, Nabai L, Granville DJ. Granzyme B in Epithelial Barrier Dysfunction and Related Skin Diseases. Am J Physiol Cell Physiol. (In press)
Research Interest
Aging; Cardiovascular health; dermatology; extracellular matrix; Granzymes; inflammation; proteases; remodelling; Tissue injury; Wound healing
Dr. Granville’s research program over the past 20 years has been focused on mechanisms by which tissues are injured and identifying therapeutic targets that can be exploited to reduce injury and/or promote healing. His research is presently focused on how aging, immobility and diabetes affect tissue injury, inflammation and repair in different types of tissues. Dr. Granville has identified a family of serine proteases, known as Granzymes (Granule-secreted enzymes) that are elevated and contribute to the pathogenesis of conditions associated with impaired healing and inflammation, including autoimmune diseases (eg. multiple sclerosis, discoid lupus erythematosus), pressure/diabetic ulcers, spinal cord injury, cardiovascular, pulmonary and skin injury. In order to study granzymes in such a diverse set of indications, Dr. Granville has established an extensive network of clinical and scientific collaborators. He is currently taking this research to the next level with respect to translating his discoveries into the development and commercialization of novel, first-in-class therapeutics with the goal of entering the clinic by the end of 2017. Since arriving at UBC, his research has resulted in the filing of 30 patents, of which, all are owned by UBC and licensed to industry, and all include his UBC trainees as co-inventors. He is also the Scientific Founder and serves as the Chief Scientific Officer of the UBC spin-off company, viDA Therapeutics, Inc.
Dr. Granville is a Professor in the Pathology Laboratory of Medicine and a Principal Investigator in ICORD at UBC. He is the Associate Director of the BC Professional Firefighters’ Burn and Wound Healing Research Laboratory. He obtained his Ph.D. in Experimental Pathology at UBC.
At ICORD, Dr. Granville’s team is expanding on the work they have done on pressure ulcers with the Rick Hansen Institute and will be applying their expertise in Granzymes to areas related to spinal cord injury and multiple sclerosis, such as the role of Granzymes in neuronal damage and demyelination. He also has an established program investigating the role of granzymes in dermatological disorders and cardiovascular diseases.
Current Projects In My Lab Include
Although his laboratory is quite full at the moment, Dr. Granville is always on the lookout for talented, energetic and bright graduate students and post-doctoral fellows to join his team if funding is available. Please contact Dr. Granville with inquiries.