Molecular and Translational Cardiology
Head:
Prof. Dr. med. Kai C. Wollert
W3 Professur für Molekulare und Translationale Kardiologie
Hans-Borst Center for Heart and Stem Cell Research
Phone: +49-511-532-4055
Fax: +49-511-532-5307
E-mail: wollert.kai
mh-hannover.de
Assistant:
Dr. rer. nat. Kerstin Bethmann (currently on maternity leave)
Phone: +49-511-532-5365
Fax: +49-511-532-5307
E-mail: bethmann.kerstinmh-hannover.de
Latest Developments:
Article about our work in the "Deutsches Ärzteblatt" (PDF)
New survival factor after myocardial infarction identified – Publication in Nature Medicine:
Research Focus of our Group:
We are investigating the molecular and cellular mechanisms that promote heart failure development after acute myocardial infarction (MI). Our goal is to develop more effective diagnostic and therapeutic strategies for patients with acute MI. We are especially interested in the inflammatory reaction after MI, and how it can be influenced by protein and cell therapy. To this end, we have established bioinformatic tools to identify new secreted proteins from the different cell types involved in infarct healing.
- Inflammatory cells (red) invading the infarcted heart (orange). Surviving heart muscle cells are green.
One of the proteins that we found to be highly expressed in the infarcted heart is growth-differentiation factor 15 (GDF-15). Our recent work (Nature Medicine 2011) shows that GDF-15 acts as an anti-inflammatory cytokine that limits leukocyte recruitment into the infarcted myocardium thereby limiting tissue damage and promoting survival. We have developed an immunoassay to measure GDF-15 in blood samples from patients with cardiovascular disease. We find that GDF-15 is a strong prognostic marker in patients with MI and heart failure (Circulation 2010). We have patented GDF-15 as a new cardiovascular biomarker, and we are working with Roche Diagnostics to develop a GDF-15 test kit for routine clinical use.
In a series of clinical trials, we are assessing the therapeutic potential of autologous bone marrow cells in patients with acute MI. In the BOOST study, we found that an intracoronary infusion of bone marrow cells improves the contractile performance of the heart in patients after MI (Lancet 2004). We are further exploring this concept in the ongoing double-blinded, placebo-controlled BOOST-2 trial. We think that paracrine factors released from bone marrow cells mediate these beneficial effects (Nature Reviews Cardiol 2010). Indeed, we have identified fibroblast growth factor 9 (FGF9) as one protein that is produced by bone marrow cells and that promotes angiogenesis and adaptive hypertrophy in mice after MI. We have developed an FGF9-based gene therapy that significantly improves survival after MI in mice (Circulation 2011).
Current Members of our Group
Scientists:
Torben Brod (torbenbrodgmx.de)
PD Dr. rer. nat. Karsten Grote (grote.karstenmh-hannover.de)
PD Dr. med. Tibor Kempf (kempf.tibormh-hannover.de)
Dr. rer. nat. Stefanie Klede (klede.stefaniemh-hannover.de)
Dr. rer. nat. Mortimer Korf-Klingebiel (korf.mortimermh-hannover.de)
Dr. rer. nat. Marc Reboll (reboll.marcmh-hannover.de)
Dr. med. Heike Tapken (tapken.heikemh-hannover.de)
Dr. med. Christian Widera (widera.christianmh-hannover.de)
Christian Willenbockel (christianwillenbockelgmx.de)
Technicians and Study Nurses:
Eva Brinkmann (brinkmann.evamh-hannover.de)
Juliane Ebersold (ebersold.julianemh-hannover.de)
Anna Kanwischer (kanwischer.annamh-hannover.de)
Ivonne Marquardt (marquardt.ivonnemh-hannover.de)
Anja Guba-Quint (guba-quint.anjamh-hannover.de)
Ines Reimann (reimann.inesmh-hannover.de)
Grant Support:
Deutsche Forschungsgemeinschaft
Bundesministerium für Bildung und Forschung
German Israeli Foundation
Fondation Leducq
Roche Diagnostics
Roche Pharma
Polyphor Ltd.
Honors and Awards:
Prof. Wollert:
2009 European Society of Cardiology, Council for Basic Cardiovascular Science Outstanding Achievement Award
2007 Jan-Brod-Preis der Gesellschaft der Freunde der MHH
2007 Arthur-Weber-Preis der Deutschen Gesellschaft für Kardiologie
2006 Innovationspreis der Deutschen Hochschulmedizin
2006 Albert-Fraenkel-Preis der Deutschen Gesellschaft für Kardiologie
2004 Karl-Ludwig-Neuhaus Forschungspreis der ALKK und der Deutschen Gesellschaft für Kardiologie
PD Dr. Grote:
2008 Ernst-Eickhoff Preis der Medizinischen Hochschule Hannover
PD Dr. Kempf:
2009 Hans Blömer Young Investigator Award (2. Platz), Deutsche Gesellschaft für Kardiologie
2009 Forschungspreis der René Baumgart Stiftung
Recent Publications from the Lab:
Kempf T, Zarbock A, Widera C, Butz S, Stadtmann A, Rossaint J, Bolomini-Vittori M, Korf-Klingebiel M, Napp LC, Hansen B, Kanwischer A, Bavendiek U, Beutel G, Hapke M, Sauer MG, Laudanna C, Hogg N, Vestweber D, Wollert KC. GDF-15 is an inhibitor of leukocyte integrin activation required for survival after myocardial infarction in mice. Nat Med. 2011;17:581-588.
Korf-Klingebiel M, Kempf T, Schlüter KD, Willenbockel C, Brod T, Heineke J, Schmidt VJ, Jantzen F, Brandes RP, Sugden PH, Drexler H, Molkentin JD, Wollert KC. Conditional transgenic expression of fibroblast growth factor 9 in the adult mouse heart reduces heart failure mortality after myocardial infarction. Circulation. 2011;123:504-514.
Bonaca MP, Morrow DA, Braunwald E, Cannon CP, Jiang S, Breher S, Sabatine MS, Kempf T, Wallentin L, Wollert KC. Growth differentiation factor-15 and risk of recurrent events in patients stabilized after acute coronary syndrome. Observations from PROVE IT-TIMI 22. Arterioscler Thromb Vasc Biol. 2011;31:203-210.
Anand IS, Kempf T, Rector TS, Tapken H, Allhoff T, Jantzen F, Kuskowski M, Cohn JN, Drexler H, Wollert KC. Serial measurement of growth-differentiation factor-15 in heart failure: relation to disease severity and prognosis in the Valsartan Heart Failure Trial. Circulation. 2010;122:1387-1395.
Wollert KC, Drexler H. Cell therapy for the treatment of coronary heart disease: a critical appraisal. Nature Reviews Cardiol. 2010;7:204-215.