School of Biomedical Sciences cordially invites you to join the following seminar:

Speaker: Professor Thomas Braun, Director, Max-Planck-Institute for Heart and Lung Research, Professor of Medicine, Justus-Liebig-University Giessen, Germany
Talk Title: Manipulation of inflammation and regeneration in the diseased heart

Date: 14 February 2025 (Friday)
Time: 4:00 pm – 5:00 pm
Venue: Seminar Room 3, G/F, Laboratory Block, 21 Sassoon Road
Host: Professor Ralf Jauch

Biography

Thomas Braun is director at the Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany and Professor of Medicine at the Justus-Liebig-University Giessen, Germany. He studied medicine and philosophy at the Universities of Göttingen and Hamburg, where he obtained his MD and MD PhD. After postdoctoral training in Hamburg and in Boston in the lab of Rudolf Jaenisch at the Whitehead Institute, MIT he became group leader at the Technical University of Braunschweig in 1992 before he moved on to an associate professor position at the University of Würzburg in 1996. After that he was appointed full professor and chair of Physiological Chemistry at the University of Halle-Wittenberg. In 2004 he was recruited by the Max-Planck-Society as founding director of the newly established Max-Planck-Institute for Heart and Lung Research in Bad Nauheim. Since 2004 he is also Professor of Medicine at the University of Giessen, Germany. So far, he has published more than 400 papers in leading journals including Nature, Science, Nature Medicine, Nature Immunology Cell, Cell Stem Cell, Developmental Cell, Cell Metabolism, EMBO J, Circulation, Circ. Res. and others His primary research currently focuses on the mechanisms driving skeletal and cardiac muscle development, regeneration and remodeling. He serves on various committees and advisory boards in Germany and abroad. He is an elected member of the German National Academy of Science, Leopoldina and the Academy of Europe and is editorial board member of several journals. Furthermore, he is in the steering board of several national and international research consortia and director of the Cardiopulmonary Institute Frankfurt, Bad Nauheim, Giessen).

Abstract

Heart failure, often triggered by acute myocardial infarction, is an increasingly prevalent disease characterised by loss of cardiomyocytes, inflammation, accumulation of fibrosis, chamber remodelling, and reduced cardiac output. Adequate control of inflammation after myocardial infarction is critical for efficient repair and sets the stage for tissue regeneration.

We found that Regenerating islet-derived proteins (REGs) regulate recruitment of immune-modulatory macrophages to the site of myocardial damage. Genetic inactivation of Reg3β causes prolonged persistence of neutrophil granulocytes (Nphs) within damaged regions, associated with cardiac rupture. Intriguingly, Reg3β binds to a subset of Nphs, induces cell death and thereby terminates inflammation. Our data indicate that Reg genes are part of an endogenous regulatory loop that restricts the persistence of Nphs in the infarcted heart to ensure efficient myocardial healing and/or regeneration.

Immune processes are critical for neonatal heart regeneration in mice and also instrumental for inducing partial dedifferentiation of cardiomyocytes after myocardial infarction. We pursued different approaches to promote dedifferentiation of cardiomyocytes, including transiently expression of the reprogramming factors OSKM. Furthermore, we found that enforced conversion of mature to immature energy metabolism is sufficient to induce cardiomyocyte de-differentiation and eventually heart regeneration.

Heart failure is not only caused by ischemic cardiomyopathy but also by mutations resulting in formation of protein aggregates, leading to dilative cardiomyopathy (DCM). We identified the ubiquitin-specific peptidase 5 (USP5) as a critical determinant of protein quality control in cardiomyocytes. Cardiac-specific overexpression USP5 reduces pathological remodeling in pressure-overloaded mouse hearts and attenuates protein aggregate formation in titinopathy and desminopathy models. Interestingly humans with end-stage DCM show lower USP5 levels, suggesting that reduced presence of USP5 contributes to the pathogenesis of DCM.

ALL ARE WELCOME.