Natural immunity and atherosclerosis
Atherosclerosis, cytokines, innate immunity, natural antibodies, complement, lipid peroxidation, oxidized LDL, microparticles.
Dr. Binder is interested in the immune mechanisms of atherogenesis 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. Currently, his laboratory is 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.
Collaborating research groups where PhD Students can perform their research stay
Dr. Ziad Mallat, Division of Cardiovascular Medicine, University of Cambridge, Addenbrooke’s Hospital, Cambridge, CB2 2QQ, UK.
Dr. Joseph L. Witztum, Dept. of Medicine, University of California San Diego, 1080 BSB, 9500 Gilman Drive, La Jolla, CA-92093-0682, USA
Dr. Ronit Shiri-Sverdlov, Department of Genetics and Cell Biology, Maastricht University Medical Centre, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands
Know-how and infrastructure of the research group
Dr. Binder is an expert in the immunology of atherosclerosis. He first described the atheroprotective role of the natural IgM antibody T15/EO6 (Binder et al., 2003), which was followed by studies defining protective mechanisms of T15/EO6 (Chang et al., 2004; Imai et al., 2008). He also was the first to identify the atheroprotecive role of IL-5 in mice and then humans (Binder et al., 2004; Sämpi et al., 2008). Subsequently, his research group has demonstrated that oxidation-specific epitopes are major targets of natural IgM antibodies (Chou et al., 2009) and identified the functional role for complement factor H in protecting against the consequences of oxidative stress (Weismann et al., 2011).
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 will be 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.