Christine T.N. Pham, M.D.

Associate Professor
Internal Medicine
Rheumatology
Pathology and Immunology

Immunology Program
Molecular Genetics and Genomics Program

  • 314-362-9043

  • 314-747-4696

  • 314-454-1091

  • 8045

  • 6621 Clinical Sciences Research Building

  • CPHAM@WUSTL.EDU

  • autoimmunity, inflammation, innate immunity, nanotechnology, protease

  • Immunity and autoimmunity in inflammatory diseases; nanotherapy in the treatment of inflammatory diseases

Research Abstract:

One focus of our laboratory is to define the role of proteases in immunity and autoimmunity. Traditionally proteases are viewed as degradative enzymes owing to their ability to digest extracellular matrix (ECM). More recently, studies have established that proteases are key molecules involved in the regulation of leukocyte recruitment at site of inflammation. Loss-of-function mutations in several serine proteases and the cysteine protease cathespin C rendered mice resistant to experimentally induced arthritis, death in a model of sepsis, elastase-induced abdominal aortic aneurysm, and Sendai virus-induced asthma phenotype. Therefore, a more complete understanding of the functional physiology of proteases should lead to a better understanding of immune effector cell biology and may potentially lead to novel therapeutic interventions for various autoimmune and inflammatory conditions.

Another focus of my laboratory is to develop targeted nanomedicine strategies to halt or reverse joint degeneration in preclinical models of rheumatoid arthritis (RA) and osteoarthritis (OA). These projects represent an interdisciplinary nanomedicine approach to arthritis research, which combines the expertise of my laboratory in various animal models of arthritis 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 or siRNAs specifically to the joints to halt the progression of arthritis in mouse models of RA and OA.Targeted nanomedicine therefore represents a promising novel approach that will allow concentrated delivery of therapeutics to specific sites (joints) while minimizing systemic side effects.

Selected Publications:

Yan H, Duan X, Pan H, Holguin N, Rai MF, Akk A, Springer LE, Wickline SA, Sandell LJ, Pham CTN. Suppression of NF-kB activity via nanoparticle-based siRNA delivery alters early cartilage responses to injury. Proc Natl Acad Sci USA. 2016, 113:E6199-E6208

Akk A, Springer LE, Pham CTN. Neutrophil extracellular traps enhance early inflammatory response in Sendai virus-induced asthma phenotype. Front Immunol. 2016, 7:325. doi: 10.3389/fimmu.2016.00325

Yan H, Zhou H-F, Akk A, Hu Y, Springer LE, Ennis TL, Pham CTN. Neutrophil proteases promote abdominal aortic aneurysm via NET formation and type I interferon induction. Aterioscler Thromb Vasc Biol. 2016, 36:1660-9.PMCID: PMC4965335

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-κB p65 subunit suppress nascent experimental arthritis. J Clin Invest. 2014, 124:4363-4374. PMCID: PMC4191028

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. PMCID: PMC4108210

Zhou H-F, Yan H, Stover CM, Montes Fernandez T, Rodriguez de Cordoba S, Song W-C, Wu X, Thompson RW, Schwaeble WJ, Atkinson JP, Hourcade De, Pham CTN. Antibody directs properdin-dependent activation of the complement alternative pathway in a mouse model of abdominal aortic aneurysm. Proc Natl Acad Sci USA. 2012, 109:E415-422. PMCID: PMC3289386

Pagano MB, Zhou H, Ennis TL, Wu X, Lambris JD, Atkinson JP, Thompson RW, Hourcade DE, and Pham CTN. Complement-dependent neutrophil recruitment is critical for the development of elastase-induced abdominal aortic aneurysm. Circulation 2009, 119:1805-1813. PMCID: PMC2758616

Pagano MB, Bartoli MA, Ennis TL, Mao D, Simmons PM, Thompson RW, and Pham CTN. Critical role of dipeptidyl peptidase I in neutrophil recruitment during abdominal aortic aneurysm development. Proc Natl Acad Sci USA 2007 104: 2855-2860. PMCID: PMC1797622

Pham CTN. Neutrophil serine proteases: Specific regulators of inflammation. Nature Rev Immunol 2006 6: 541-550.

Raptis SZ, Shaprio SD, Simmons PM, Cheng AM, Pham CTN. Serine protease cathepsin G regulates adhesion-dependent neutrophil effector functions by modulating integrin clustering. Immunity 2005 22: 679-691.

Last Updated: 7/25/2018 8:13:15 AM

Back To Top

Follow us: