Dr. Binder is interested in the immune mechanisms of atherosclerosis and the immune recognition of oxidation-specific epitopes, and particularly how these responses can be exploited to protect from atherosclerotic lesion formation. His interests are clearly interdisciplinary and span vascular biology, lipid oxidation, natural antibodies and innate immunity. In the past years, Dr. Binder’s research has focused on the identification and characterization of germline encoded natural IgM antibodies as well as of soluble pattern recognition proteins, such as complement factor H, that bind oxidation-epitopes. His laboratory is currently defining the functional role of B-cells and natural IgM antibodies as well as complement regulators using mouse models of atherosclerosis. Another important focus of Dr. Binder’s research interests is on the inflammatory response of macrophages to defined oxidation-epitopes, such as malondialdehyde-adducts, and the role of circulating microparticles as carriers of biologically active oxidized lipids.
Christoph Binder’s laboratory focuses on the role of immune responses in atherosclerosis. Projects aim at the characterization of innate immune responses that mediate the recognition of lipid-peroxidation derived epitopes, and major efforts focus on the characterization of immune responses to malondialdehyde-epitopes. In addition, the role and function of B-cell subsets and natural antibodies specifically are being investigated.
techniques and infrastructure of the research group:
The group utilizes mouse models of atherosclerosis in combination with various immune deficient models for morphometric analyses of the extent of atherosclerosis and assessment of lesion phenotype by immunohistochemistry (Binder et al., 2003). Major techniques used include a wide array of immunological assays, flow cytometry, FACSorting, adoptive in vivo cell transfer and bone marrow transplantation (Binder et al., 2004; Chang et al. 2004); the biochemical generation of oxidized lipid antigens/ligands and standard molecular biology and cell culture techniques. Group members have access to a fully equipped cell culture facility, FACS sorter and analyzers, microtiter plate readers, ultracentrifuge, HPLC, FPLC, PCR equipment (incl. multichannel Real-time PCR), next generation sequencing equipment, cryo- and microtome, and a fluorescent microscope with imaging equipment. Animal experiments are performed at the Medical University's mouse facility, which is located in the same building and provides all necessary support, incl. trained animal care-takers and veterinarians.
Amir, S., K. Hartvigsen, A. Gonen, G. Leibundgut, X. Que, E. Jensen-Jarolim, O. Wagner, S. Tsimikas, J. L. Witztum, and C. J. Binder. 2012. Peptide mimotopes of malondialdehyde epitopes for clinical applications in cardiovascular disease. J Lipid Res 53: 1316-1326.
Weismann, D., K. Hartvigsen, N. Lauer, K. L. Bennett, H. P. Scholl, P. Charbel Issa, M. Cano, H. Brandstatter, S. Tsimikas, C. Skerka, G. Superti-Furga, J. T. Handa, P. F. Zipfel, J. L. Witztum, and C. J. Binder. 2011. Complement factor H binds malondialdehyde epitopes and protects from oxidative stress. Nature 478: 76-81.
Chou, M. Y., L. Fogelstrand, K. Hartvigsen, L. F. Hansen, D. Woelkers, P. X. Shaw, J. Choi, T. Perkmann, F. Backhed, Y. I. Miller, S. Horkko, M. Corr, J. L. Witztum, and C. J. Binder. 2009. Oxidation-specific epitopes are dominant targets of innate natural antibodies in mice and humans. J Clin Invest 119: 1335-1349.
Binder, C. J., K. Hartvigsen, M. K. Chang, M. Miller, D. Broide, W. Palinski, L. K. Curtiss, M. Corr, and J. L. Witztum. 2004. IL-5 links adaptive and natural immunity specific for epitopes of oxidized LDL and protects from atherosclerosis. J Clin Invest 114: 427-437.
Binder, C. J., S. Horkko, A. Dewan, M. K. Chang, E. P. Kieu, C. S. Goodyear, P. X. Shaw, W. Palinski, J. L. Witztum, and G. J. Silverman. 2003. Pneumococcal vaccination decreases atherosclerotic lesion formation: molecular mimicry between Streptococcus pneumoniae and oxidized LDL. Nat Med 9: 736-743.