This proposal describes a 5 year training program for the development of an academic career in rheumatology. The principal investigator has completed formal fellowship training in rheumatology at the University of California in Los Angeles (UCLA) and is currently finishing work for a master's degree in clinical research methodology. This unique, interdisciplinary training program will build upon the candidate's clinical science background, expanding her skills in areas of laboratory research, biostatistics, and epidemiology in order for successful development as an independent translational researcher. Dr. Srinivasa T. Reddy, co-director of the Center for Biomarker Discovery at UCLA and a recognized leader in atherosclerosis and lipoprotein research, and Dr. Daniel E. Furst, director of the Rheumatology Clinical Trials Center at UCLA and an expert in clinical investigation, will co-mentor the principal investigator's scientific development. Research will focus on the functional role of lipoproteins in inflammation and premature atherosclerosis in patients with rheumatoid arthritis (RA). Work in Dr. Reddy's lab has suggested that the anti- or pro-inflammatory nature of HDL function is a more sensitive indicator of atherosclerosis than standard HDL cholesterol levels. Abnormal, pro-inflammatory HDL is more common in RA patients than healthy controls and recent work by the candidate suggests that it is associated with increased disease severity, activity, and increased haptoglobin in HDL.
Specific aims i nclude: 1) To determine whether abnormal HDL anti-inflammatory function contributes to Increased atherosclerosis in patients with RA by examining its association with carotid intima wall thickness and plaque in a cohort of 240 RA patients. 2)To determine whether specific protein components of HDL are associated with a) abnormal HDL function, b) atherosclerosis, and c) disease activity in RA. 3) To determine the cumulative effects of RA disease activity on HDL function and HDL-associated proteins in a cross sectional RA cohort followed for three years.
^: Identification of biomarkers that indicate a mechanism for early atherosclerosis in patients with RA is an important step in preventing morbidity from cardiovascular disease (CVD) in this population. Characterization of HDL dysfunction may further our understanding of why RA patients are at increased risk for CVD, and may also guide us in the development of new strategies to significantly impact CV morbidity and mortality.
|Navarro-Millan, Iris; Charles-Schoeman, Christina; Yang, Shuo et al. (2013) Changes in lipoproteins associated with methotrexate or combination therapy in early rheumatoid arthritis: results from the treatment of early rheumatoid arthritis trial. Arthritis Rheum 65:1430-8|
|Charles-Schoeman, Christina; Lee, Yuen Yin; Shahbazian, Ani et al. (2013) Association of paraoxonase 1 gene polymorphism and enzyme activity with carotid plaque in rheumatoid arthritis. Arthritis Rheum 65:2765-72|
|Charles-Schoeman, Christina; Lee, Yuen Yin; Grijalva, Victor et al. (2012) Cholesterol efflux by high density lipoproteins is impaired in patients with active rheumatoid arthritis. Ann Rheum Dis 71:1157-62|
|Watanabe, Junji; Charles-Schoeman, Christina; Miao, Yunan et al. (2012) Proteomic profiling following immunoaffinity capture of high-density lipoprotein: association of acute-phase proteins and complement factors with proinflammatory high-density lipoprotein in rheumatoid arthritis. Arthritis Rheum 64:1828-37|