About Our Group

Our lab focuses on the discovery, development and clinical translation of novel targets for heart failure (HF) therapy. HF, the disability of the cardiac muscle to provide sufficient circulatory support at rest and exercise, currently has limited treatment options and patients suffering from severe HF (NYHA III/IV) face a 5-year mortality > 50%. In light of this therapeutic dilemma, our research efforts are targeted towards innovative treatments emerging from the investigation of the physiological role, pathophysiological relevance and therapeutic potential of S100 proteins in cardiac and vascular disease. 

In the last decade, our group pioneered research focusing on the role of S100 proteins in cardiovascular physiology and disease. In particular, we characterized S100A1, being the cardiac specific S100 isoform, as a novel calcium-dependent inotrope with anti-arrhythmic and anti-apoptotic properties. S100A1s unique inotropic actions in the heart are independent and additive to beta-adrenergic stimulation and cAMP-PKA dependent signaling. Our work shows that loss of S100A1 in diseased myocardium is a critical factor in heart failure development and progression. Based on these results, we have successfully developed viral- and peptide-based therapeutic approaches to restore S100A1 protein function that can rescue heart failure in different experimental cardiac disease models. Our gene therapy approaches are currently tested in a large animal heart failure model in order to enter clinical testing.

An exciting new option stems from our recent insight into therapeutic options of S100A1 derived peptides. Given the unresolved biological concerns regarding viral-based approaches, S100A1 derived peptides with the identical therapeutical profile than the native protein enable novel and exciting therapeutic options that are currently tested in cellular and small animal HF models. In addition, we have extended our research focus into S100A1 function in endothelial cells and pertinent regulation of vascular function and blood pressure. Although expressed at significantly lower levels than in cardiomyoctes, our lab most recently provided evidence for a crucial role of endothelial S100A1 in endothelial cell NO-homeostasis and blood pressure regulation. Given the world-wide significance of hypertensive disease, our translational efforts are directed towards development of novel S100A1-based anti-hypertensive therapeutic strategies. 

Due to known extracellular S100 functions, we have most recently identified S100A1 as a novel cardiac alarmin being released upon ischemic damage from cardiomyocytes in the extracellular environment and circulation. S100A1 participates in healing after myocardial infarction (MI) through modulation of post-MI inflammation and recruitment of stem cells to the site of cardiac injury. 
Our efforts are directed towards therapeutic use and manipulation of MI-released S100A1 to improve post-MI healing and regeneration. 

Team

Alumni:

Dr. rer. nat. Martin Busch (Wissenschaftlicher Laborleiter) 
Dr. rer. nat. Michael Egger (Wissenschaftlicher Mitarbeiter) 
Moritz Hippchen (Humanmedizinischer Doktorand) 
Hannah Bürkert (Humanmedizinische Doktorandin) 
Dr. rer. nat. Fadwa El Tahry Abdalla (PhD Studentin) 
Johanna Sophie Ferdinand (MTA) 
Thien-Kim Bui (Humanmedizinische Doktorandin) 
Michael Daszenies (Humanmedizinischer Doktorand) 
Viktoria Mertin (Humanmedizinische Doktorandin) 
Meike Schrader (Humanmedizinische Doktorandin) 
Philipp Thiele (Humanmedizinischer Doktorand) 
Jasmin Krömer (geb. Hoffmann) (MTA)
Dr. rer. nat. Karl Varadi (Wissenschaftlicher Mitarbeiter)
Dr. rer. nat. Mandy Kossack (Wissenschaftliche Mitarbeiterin)
Fabian Günther (Humanmedizinischer Doktorand)
Dr. rer. nat. Julia Ritterhoff (Wissenschaftliche Mitarbeiterin)
Michelle Blomgren  (Parlamentarisches Patenschaftsprogramm)
Nicole Herzog (MTA)
Chelsea Merkel  (DAAD RISE)
Isabel Krämer (Masterstudentin)
Dr. med. Carolin Lerchenmüller (Assistenzärztin)
Dr. rer. nat. Mauro Siragusa (Wissenschaftlicher Mitarbeiter)
Jasmin Koehler (Veterinärmedizinische Doktorandin)
Ieva Didrihsone  (Humanmedizinischer Doktorandin)
Anne Volkert (PhD Studentin, Biol. Doktorandin)
Andreas Seitz (Humanmedizinischer Doktorand)
Birgit Krautz (Veterinärmedizinische Doktorandin)
Irina Neacsu (Veterinärmedizinische Doktorandin)
Lukas Adrian (Humanmedizinischer Doktorand)
Nils Gade (Humanmedizinischer Doktorand)
Jemmy Zhao (Humanmedizinischer Doktorand)
Ange Zhang (Humanmedizinischer Doktorand)
Christoph Schön (Humanmedizinischer Doktorand)

Kooperationen

Freiburg Institute for Advanced Studies – FRIAS, Albert-Ludwigs-Universität Freiburg, Germany

Center for Translational Medicine, Thomas Jefferson University, Philadelphia, PA, USA

Maurice E. Müller Institute, Biozentrum Basel, Universität Basel, Switzerland

Institute of Biomedical Life Sciences (IBLS), University of Glasgow, United Kingdom

Deutsches Krebsforschungszentrum, DKFZ, Heidelberg, Germany

Nationales Centrum für Tumorerkrankungen, NCT, Heidelberg, Germany

Herzchirurgie, Herzzentrum des Universitätsklinikums Heidelberg, Heidelberg, Germany

Radiologische Klinik und Poliklinik, Universitätsklinikum Heidelberg, Heidelberg, Germany

San Diego Heart Institute, San Diego State University, San Diegeo, CA, USA

Wissenschaftliche Gesellschaften

Deutsche Gesellschaft für Kardiologie – German Society of Cardiology

European Society of Cardiology

Deutsche Gesellschaft für Innere Medizin – German Society for Internal Medicine

American Heart Association (AHA) –Council of Basic and Cardiovascular Sciences

American Society of Biochemistry and Molecular Biology (ASBMB) 

Member of the Scientific Cardiovascular disease Committee of the

European Sociaty of Gene and Cell Therapy

American Society of Gene and Cell Therapy

Kontakt