Christine Pham, MD
Treating patients with rheumatic disease and educating the next generation of rheumatologists.
The focus of my laboratory is to define the role of innate immunity in various inflammatory processes. Through the use of several loss-of-function mutations in neutrophil-derived proteases and complement proteins, my laboratory has determined the contribution of neutrophils and the complement system to several experimental models of inflammation, including rheumatoid arthritis, abdominal aortic aneurysm, and asthma. I am collaborating with Drs. Dennis Hourcade, John Atkinson, and Eli Roberson in the Division of Rheumatology to develop complement inhibitors in the hope of mitigating inflammation in these disease processes.
Another focus of my laboratory is to develop targeted nanomedicine strategies to halt or reverse joint inflammation in preclinical models of rheumatoid arthritis. The project is an interdisciplinary nanomedicine approach to rheumatoid arthritis research, which combines the expertise of my laboratory in various animal models of inflammation with the strengths of the Center for Applied Nanomedicine at Washington University. The data so far indicate that targeted nanomedicine can deliver anti-angiogenic drugs specifically to the joints and halt the progression of inflammatory arthritis in a mouse model of RA. We have also shown that gene silencing using nanoparticles to deliver siRNA specifically to the inflamed joints abrogates disease progression. Targeted nanomedicine therefore represents a promising novel approach that will allow concentrated delivery of drugs specifically to the sites of inflammation while minimizing systemic side effects.
- Pham CTN, Mitchell LM, Huang JL, Lubniewski CM, Schall OF, Killgore JK, Pan D, Wickline SA, Lanza GM, and Hourcade DE. Variable antibody-dependent activation of complement by functionalized phospholipids nanoparticle surfaces. J Biol. Chem. 2011, 286:123-130
- Schreiber A, Pham CTN, Hu Y, Schneider W, Luft FC, Kettritz R. Neutrophil serine proteases promote IL-1 generation and injury in necrotizing crescentic glomerulonephritis. J. Am. Soc. Neprhol. 2012, 23:470-482
- Zhou H-F, Yan H, Senpan A, Wickline SA, Pan D, Lanza GM, PhamCTN. Suppression of inflammation in a mouse model of rheumatoid arthritis using targeted lipase-labile fumagillin prodrug nanoparticles. Biomaterials 2012, 33:8632-40
- Zhou H-F, Yan H, Cannon JL, Springer LE, Green JM and Pham CTN. CD43-mediated IFN-g production by CD8+ T cells promotes abdominal aortic aneurysm in mice. J. Immunol. 2013, 190:5078-5085
- Zhou H-F, Yan H, Bertram P, Hu Y, Springer LE, Thompson RW, Curci JA, Hourcade DE, Pham CTN. Fibrinogen-specific antibody induces abdominal aortic aneurysm in mice through complement lectin pathway activation. Proc. Natl. Acad. Sci. USA 2013, 110:E4335-4344
- Pham CTN, Thomas DG, Beiser J, Mitchell LM, Huang JL, Senpan A, Hu G, Gordon M, Baker NA, Pan D, Lanza GM, Hourcade DE. Application of hemolysis assay for analysis of complement activation by perfluorcarbon nanoparticles. Nanomedicine:NBM 2014
- Zhou H-F, Yan H, Hu Y, Springer LE, Yang X, Wickline SA, Pan D, Lanza GM, Pham CTN. Fumagillin prodrug nanotherapy suppresses macrophage inflammatory response via endothelial nitric oxide. ACS Nano 2014, 8:7305-7317
- Zhou H-F, Yan H, Pan H, Hou KK, Akk A, Springer LE, Hu Y, Allen JS, Wickline SA, Pham CTN. Peptide-siRNA nanocomplexes targeting the NF-kB p65 subunit suppress nascent experimental arthritis. J. Clin. Invest. 2014, 124:4363-4374
- Herias MV, Heeneman S, Beckers C, Bai L, Delsing D, Deamen MJ, Pham CTN, Biessen EAL. Leukocyte cathepsin C deficiency attenuates atherosclerotic lesion progression by selective tunning of innate and adaptive immune responses. Arterioscler. Thromb. Vasc. Biol. 2015, 35:79-86
- Bertram P, Akk A, Zhou H-F, Pham CTN, Hourcade DE. Anti-mouse properdin TSR 5/6 monoclonoal antibodies block complement alternative pathway-dependent pathogenesis. Monoclon. Antib. Immunodiagn. Immunother. 2015; 34:1-6
- Yan H, Zhou H-F, Hu Y, Pham CTN. Suppression of experimental arthritis through AMP-activated protein kinase activation and autophagy modulation. J Rheum Dis Treat 2015, 1:5.