Dennis Hourcade, PhD
- The complement system is a first line of defense of the intravascular space: Complement rapidly recognizes foreign entities and marks them for clearance and/or lysis. While complement is a critical innate immune system, it is also a principal cause of undesirable tissue damage. Of the three complement activation pathways, the alternative pathway (AP) in particular has been implicated in numerous disease and injury states including age-related macular degeneration and arthritis. We have long investigated the assembly, regulation and function of the alternative pathway C3 convertase, a key player of the AP, and we are now focusing on its potential as a therapeutic target.
- Nanoparticles offer new options for medical diagnosis and therapeutics with their capacity to specifically target cells and tissues with imaging agents and/or drug payloads. The unique physical aspects of nanoparticles present new challenges for this promising technology: Nanoparticles can often elicit moderate to severe complement activity that can be harmful. Our goal is to facilitate the therapeutic use of nanoparticles by understanding and controlling nanoparticle-dependent complement activation.
- Pham CTN, Mitchell LM, Huang JL, Lubniewski CM, Schall OF, Killgore JK, Pan D, Wickline SA, Lanza GM, Hourcade DE, Variable antibody-dependent activation of complement by functionalized phospholipid nanoparticle surfaces. J. Biol. Chem. 2011: 286: 123-130
- Hourcade DE, Mitchell LM, Access to the complement factor B scissile bond is facilitated by association of Factor B with C3b protein. J. Biol. Chem. 2011: 286: 35725-35732.
- 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
- Thurman JM, Kulik L, Orth H, Wong M, Renner B, Sargsyan SA, Mitchell LM, Hourcade DE, Hannan JP, Kovacs JM, Coughlin B, Woodell AS, Pickering MC, Rohrer B, Holers VM, Detection of complement activation using monoclonal antibodies against C3d. J Clin Invest. 2013: 123(5): 2218–2230.
- Zhou H-F, Yan H Bertram P, Springer LE, Hu Y, Thompson RW, Curci JA, Hourcade DE, Pham CTN, A fibrinogen-specific antibody induces abdominal aortic aneurysm in mice through complement lectin pathway activation. Proc. Natl. Acad. Sci. USA 2013: 110:E4335-4344.
- Park HJ, Guariento M, Maciejewski M, Hauhart R, Tham W-H, Cowman AF, Schmidt CQ, Mertens H, Liszewski MK, Hourcade DE, Barlow PN, Atkinson JP, Using mutagenesis and structural biology to map the binding site for the Plasmodium falciparum merozoite protein PfRh4 on the human immune adherence receptor. J. Biol. Chem. 2014: 289: 450-463.
- 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 a hemolysis assay for analysis of complement activation by perfluorocarbon nanoparticles. Nanomedicine: Nanotechnology, Biology and Medicine 2014:10:651-660.
- Thomas DG, Chikkagoudar S, Heredia-Langer A, Tardiff MF, Zhixiang X, Hourcade DE, Pham CTN, Lanza GM, WeinbergerKQ, Baker NA Physicochemical signatures of nanoparticle-dependent complement activation. Computational Science & Discovery 2014:7(1) Article 015003.
- Bertram P, Akk T, Zhou H-F, Mitchell LM, Pham CTN, and Hourcade DE Anti-mouse properdin TSR 5/6 monoclonal antibodies block complement alternative pathway-dependent pathogenesis Monoclonal Antibodies in Immunodiagnosis and Immunotherapy 2015: 34:1-6.