Russell Paul Bowler, MD, PhD
Year elected: 2017
Current membership category: Active
National Jewish Health
1400 Jackson Steet
Denver, CO 80206
United States of America
Phone: 303 398 1801
Email: bowlerr@njhealth.org

Biographical statement

My research focuses on integrating Omic technology to identify susceptibility and resistance factors to developing lung disease in smokers. We initially studied the role of oxidative stress in lung disease and then sequenced human SOD3 to identify variants associated with chronic obstructive pulmonary disease (COPD). One naturally occurring single nucleotide polymorphism SOD3, which causes an arginine (positive) to glycine (neutral) amino acid change and alters furin-mediated intracellular processing the heparin-binding region of it protein of it translated product, extracellular superoxide dismutase (EC-SOD), was noted to be protective of COPD. We then created a homologous knockin mouse to demonstrate that this change leads to impaired binding to extracellular matrix (collagen and heparin) that shifts the protein from tightly bound to tissues such as blood vessels and lungs to extracellular spaces such as plasma and lung epithelial lining fluid. This explains why human carriers of rs1799895 are more prone to cardiovascular disease (less antioxidant in blood vessels) and less prone to inhaled injury (e.g. lower risk of COPD and lung infections from higher levels of EC-SOD antioxidant in lung epithelial lining fluid). We have used several high throughput proteomics methods to identify other novel protein biomarkers of COPD and emphysema (e.g. sRAGE, ICAM1, and CCL20) with similar translation into mouse. We also use metabolomics and have identified glycoceramides and sphingomyelins as biomarkers of emphysema and correlated these signatures with novel genomic signatures such as acid ceramidase (ASAH1). Some of these signatures are currently being evaluated for biomarker qualification by FDA and EMA and will be used to risk stratify patients in clinical trials. This bedside-to-bench approach has led to improved understanding of disease pathogenesis and resilience in current and former smokers.

Institutional affiliations

National Jewish Health (Primary)

Specialties

Internal Medicine