Centre for Heart Lung Innovation
St. Paul's Hospital, Burrard Building
Rm 166 - 1081 Burrard Street, Vancouver, B.C. V6Z 1Y6
Dr. Russell pursued his undergraduate degree (AB) in Biology and Biochemistry at Princeton University and medical degree (MD) at the University of Toronto. He completed a residency in Internal Medicine at Toronto General Hospital and University of Toronto. He chose to go to the University of California, San Francisco for his Fellowship in Critical Care Medicine and research training. He then returned to Toronto General Hospital as Director of the Medical ICU before being recruited to Vancouver, BC as Director of the Medical Surgical ICU at St. Paul’s Hospital. He built a world-class team of basic science, translational, and clinical researchers in Critical Care focused on molecular mechanisms and treatment of sepsis. He was Chair of Medicine at St. Paul’s and Head of the Division of Critical Care Medicine for University of British Columbia (UBC).
He is now a Professor of Medicine at UBC, a Principal Investigator at the SPH-based Centre for Heart Lung Innovation (HLI) and a member of the Board of Molecular You and of the Personalized Medicine Initiative. Dr. Russell was also a co-founder and founding CEO of Sirius Genomics Inc., a spin off company of UBC and SPH. Sirius raised $16M to attempt to identify and validate genomic markers (i.e. predictive biomarkers) of improved response to what was the only approved drug for sepsis, activated protein C (Xigris). Dr. Russell is also co-founder and Chief Medical Officer of Cyon Therapeutics, another spin-off of UBC and SPH. Through their groundbreaking scientific discoveries the team is developing the means to boost the body’s natural ability to clear infectious toxins from the bloodstream. Bacterial toxins are found in cholesterol, so Cyon’s technology will focus on increasing the clearance of cholesterol bound toxins. The major discovery is that genetic variants of PCSK9 – loss of function variants - have improved survival from septic shock and that in murine models, PCSK9 knock-outs and antibodies to PCSK9 also have improved survival from septic shock. This important discovery has potentially important therapeutic implications in septic shock; we are now investigating the potential efficacy and safety of PCSK9 inhibitor(s) in septic shock.
Education and Training
- A.B. Biology (Cum Laude), Princeton University, 1968-1971
- M.D. Medicine, University of Toronto, 1971-1975
- Internal Medicine Residency, University of Toronto, 1975 - 1979
- Critical Care Medicine and Research Fellowship, University of California, San Francisco, 1979 - 1981
Area of Interest
The two major current themes of Dr. Russell’s research are (1) the genomics and pharmacogenomics of septic shock and (2) randomized controlled trials in patients with septic shock.
1. Genomics and Pharmacogenomics of Septic Shock
Dr. Russell has over 200 peer-review publications and continues an active research program investigating genomics of septic shock with discoveries regarding genetic variants (single nucleotide polymorphisms (SNPs)) of key coagulation, inflammatory, and innate immunity genes. We do gene association studies in: (1) septic shock and (2) cardiovascular surgery patients. Dr. Russell collaborates closely with Drs. Keith Walley and John Boyd of SPH and HLI.
Dr. Russell has held grants for genomics from CIHR to study susceptibility genes as well as peer-reviewed grants to fund studies of genotype in sepsis, post-cardiopulmonary bypass (Co- PI CIHR grant), acute respiratory distress syndrome (ARDS) (grants from BC Lung Association and Providence Health Care) and acute lung injury (ALI) (NIH SCCOR/University of Washington).
We have found significant relationships between protein C, IL-6, IL-8, IL-10, VPS13D, TNFAIP2, SVEP1, and fibrinogen genetic markers (single nucleotide polymorphisms (SNPs) and increased risk of organ dysfunction and death in sepsis. In contrast, SNPs of innate immune genes CD14, MBL, TLR-2 and TLR-1 are associated with increased risk of severe infection (sepsis).
Dr. Russell also has an active research program in pharmacogenomics of septic shock. We have identified genotypes – predictive biomarkers - that alter predicted response to therapies for septic shock including norepinephrine, activated protein C, anti-inflammatory agents, and vasopressin. We also identified the genetic mechanism of an important promotor SNP of protein C. We have also completed and are reporting the largest pharmacogenomic trial of any therapy in septic shock, a multicenter pharmacogenomic biomarker study in matched patients with severe sepsis treated with or without activated protein C.
2. Clinical Trials in Septic Shock
Dr. Russell has an active randomized controlled trials (RCTs) program in critical care (ARDS, ALI), sepsis and septic shock. We have led clinical trials of many promising drug candidates in sepsis including vasopressin in septic shock (CIHR funded), ibuprofen (NIH grant-funded), antioxidants, IL-1ra, anti-TNF, interleukin-10, tissue factor pathway inhibitor, and activated protein C.
Dr. Russell has a particular interest in vasopressin in septic shock. He was Principal Investigator of a CIHR-funded multicentre, randomized controlled trial of vasopressin vs. norepinephrine in septic shock (VASST) published in the New England Journal of Medicine (Russell JA, et al. Vasopressin vs. norepinephrine infusion in patients with septic shock. N Engl J Med 2008; 358: 877 – 887). Low dose vasopressin is comparable in efficacy and safety to norepinephrine and may be more effective than norepinephrine in less severe septic shock. The VASST study is cited in the 2008 and 2013 international sepsis treatment guidelines. To date Dr. Russell has 40 peer-reviewed publications related to vasopressin and arising from VASST as well as 12 chapters and reviews.
The activity of vasopressin can be improved by using a selective V1a agonist, selepressin. Dr. Russell was PI of a Phase 2A proof-of-principle RCT of selepressin in septic shock (Sponsor Ferring). Selepressin decreased fluid overload and need for vasopressors and ventilation.
Dr. Russell’s research success in sepsis was recognized by a prestigious invited review in the New England Journal of Medicine (Russell JA. Management of sepsis. N Engl J Med 2006; 355 (16): 699 – 713).