Atherosclerosis Immunity, Cardiovascular Neuroimmunology (Habenicht) 1

Project description

A fundamental unresolved issue in the pathogenesis of atherosclerosis is whether the advanced and clinically significant disease is associated with the generation of arterial wall-specific autoantigens recognized by autoimmune T cells or B cells (Wang et al. 2022, Zhang et al. 2022, Nature Cardiovascular Research, in revision). Our group has proposed a hypothesis how such autoimmune lymphocytes may be generated (Mohanta et al. 2014; Circulation Research; Mohanta et al. 2022, Nature; Yin et al. Nature Medicine 2019). Accordingly, we have begun to isolate germinal center B2 cells from artery tertiary lymphoid organs (ATLOs) that develop in the adventitia, i.e. the outer connective tissue coat of arteries, using aged ApoE-/- mice as the experimental model. In this challenging project, scholarship recipients will be part of a larger group of scientists to identify atherosclerosis-specific autoantigens using state-of-the art molecular biology toolkits inscluding single cell transcriptome analyses, mass spectrometry, protein biochemical tools in an international collaborative effort. The group has isolated and cloned B cell receptors from diseased arteries which are now used as baits to identify the autoantigens. Once the autoantigens will have been identified, the scholarship recipients will use in vivo models of vaccination, antibody treatment protocols to elucidate the role of the autoantigens in atherosclerosis progression. The scholarship recipient will have access to a graduate student program focusing on cardiovascular disease.