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The Max Planck Institute for Heart and Lung Research Curiosity-Driven Basic Research to Fight Cardio-Pulmonary Diseases

2017; Lippincott Williams & Wilkins; Volume: 120; Issue: 9 Linguagem: Inglês

10.1161/circresaha.117.310763

1524-4571

Thomas Braun, Stefan Offermanns, Didier Y. R. Stainier, Werner Seeger,

Cardiovascular Effects of Exercise

HomeCirculation ResearchVol. 120, No. 9The Max Planck Institute for Heart and Lung Research Curiosity-Driven Basic Research to Fight Cardio-Pulmonary Diseases Free AccessNewsPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessNewsPDF/EPUBThe Max Planck Institute for Heart and Lung Research Curiosity-Driven Basic Research to Fight Cardio-Pulmonary Diseases Thomas Braun, Stefan Offermanns, Didier Y.R. Stainier and Werner Seeger Thomas BraunThomas Braun From the Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany (T.B., S.O., D.Y.R.S., W.S.); Department of Internal Medicine II, Justus Liebig University Giessen, Germany (T.B.); Medical Faculty, Goethe University Frankfurt, Germany (S.O.); Faculty of Biological Sciences, Goethe University Frankfurt, Germany (D.Y.R.S); and Universities of Giessen & Marburg Lung Center, Department of Internal Medicine II, Germany (W.S.). , Stefan OffermannsStefan Offermanns From the Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany (T.B., S.O., D.Y.R.S., W.S.); Department of Internal Medicine II, Justus Liebig University Giessen, Germany (T.B.); Medical Faculty, Goethe University Frankfurt, Germany (S.O.); Faculty of Biological Sciences, Goethe University Frankfurt, Germany (D.Y.R.S); and Universities of Giessen & Marburg Lung Center, Department of Internal Medicine II, Germany (W.S.). , Didier Y.R. StainierDidier Y.R. Stainier From the Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany (T.B., S.O., D.Y.R.S., W.S.); Department of Internal Medicine II, Justus Liebig University Giessen, Germany (T.B.); Medical Faculty, Goethe University Frankfurt, Germany (S.O.); Faculty of Biological Sciences, Goethe University Frankfurt, Germany (D.Y.R.S); and Universities of Giessen & Marburg Lung Center, Department of Internal Medicine II, Germany (W.S.). and Werner SeegerWerner Seeger From the Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany (T.B., S.O., D.Y.R.S., W.S.); Department of Internal Medicine II, Justus Liebig University Giessen, Germany (T.B.); Medical Faculty, Goethe University Frankfurt, Germany (S.O.); Faculty of Biological Sciences, Goethe University Frankfurt, Germany (D.Y.R.S); and Universities of Giessen & Marburg Lung Center, Department of Internal Medicine II, Germany (W.S.). Originally published28 Apr 2017https://doi.org/10.1161/CIRCRESAHA.117.310763Circulation Research. 2017;120:1386–1389The Max Planck Institute for Heart and Lung Research (MPI-HLR) is an institute of the Max Planck Society (MPS), Germany's most successful research organization. The MPS is a research institution mainly sponsored by the federal and local state governments. The MPS runs 78 institutes at various locations in Germany and abroad and has an annual budget of 1.6 billion €. The different institutes belong to the Chemistry, Physics, and Technology (32 institutes), Biology and Medicine (27 institutes), or the Humanities (19 institutes) sections. Together with its predecessor institution, the Kaiser Wilhelm Society, researchers of the MPS have received no fewer than 33 Nobel prizes in different research areas. This success has been possible because of a simple principle, defined by Adolph von Harnack, the first president of the Kaiser Wilhelm Society, >100 years ago: recruit the world's leading researchers, let them freely define their research subjects with minimum interference by the leadership, and give them the best working conditions possible.About 12 years ago, the MPI-HLR was restructured, gaining its new focus on the cardiovascular and pulmonary systems. Since then, basic cardiopulmonary research is the dominant theme at the MPI-HLR, following Max Planck's motto "Insight must precede application." Numerous groundbreaking discoveries were made in the past decade, which had an enormous impact on the research community.New Institute With a Long and Rich Scientific HistoryThe MPI-HLR was originally founded in 1929 by the initiative of Prof Franz Groedel (1881–1951) and William G. Kerckhoff (1856–1929), a successful German American industrialist and science patron. Prof Franz Groedel, who served as the institute's first director until his death in New York City, was a renown German Cardiologist, a world authority in cardiac radiology, and a pioneer in electrocardiography. Prof Groedel managed to establish a cardiovascular research institute that was unmatched by anything in the United States or Europe at the time. Tragically, Prof Groedel was unable to savor the fruits of his efforts since he was forced to emigrate to the United States because of his Jewish ancestry. Formally, he remained director of the Kerckhoff Institute but stayed in the United States, where he, among many other activities, served as founder of the American College of Cardiology. In 1952, the institute became part of the MPS and flourished under the leadership of Prof Rudolf Thauer, Prof Eberhardt Dodt, Prof Eckhart Simon, Prof Werner Risau, and Prof Wolfgang Schaper.The institute's new profile took shape by recruitment of Prof Thomas Braun as the founding director in 2004, followed by Prof Werner Seeger in 2007, Prof Stefan Offermanns in 2008, and Prof Didier Stainier in 2012. The generous support by the MPS, the Kerckhoff Foundation, and the local state government of Hesse allowed construction of a new research building (Figure 1). This modern facility, which opened in 2010, offers ≈3900 m2 usable floor space and is equipped with the latest scientific equipment. Renovation of the original building (4200 m2) will be completed by the end of 2017 thereby creating additional opportunities for new principal investigators.Download figureDownload PowerPointFigure 1. Image of the new Max Planck Institute for Heart and Lung Research (MPI-HLR) research building in Bad Nauheim next to the Kerckhoff Hospital. The building was opened in spring 2010. Bottom: group photograph of the 4 department directors (from left to right, Didier Stainier, Stefan Offermanns, Werner Seeger, and Thomas Braun).Mission and StructureThe mission of the MPI-HLR is to perform cutting-edge research to gain new insights into the basic molecular mechanisms that underlie cardiovascular and lung diseases. Excellent basic research (almost) inevitably gives rise to practical applications and new therapies. Hence, the MPI-HLR works closely together with the Kerckhoff Hospital in Bad Nauheim and clinical departments at the nearby universities of Frankfurt and Giessen to put scientific discoveries into practical applications. The overall scientific mission is reflected in the focus of the institute departments and independent research groups (Figure 2A).Download figureDownload PowerPointFigure 2. A, Organization of the Max Planck Institute for Heart and Lung Research (MPI-HLR). Main cooperation partners are shown as well. B, Numbers of employees at the MPI-HLR from 2006 until 2016. C, Numbers of publications between 2006 and 2016.Currently, the institute comprises 4 departments and several independent research groups (11 principal investigators [PIs] in total). The total numbers of employees amount to 354 people , including 171 scientists (among them 75 PhD students) and 183 supporting staff (Figure 2B). The 4 departments focus on different aspects of heart and lung research, Department 1 (directed by Prof Thomas Braun) studies development and remodeling of the heart with a special emphasis on stem cells, control of proliferation, and transcriptional/chromatin-based gene regulation. Department 2 (directed by Prof Stefan Offermanns) analyzes molecular mechanisms of cellular signaling pathways (eg, G-protein–mediated signaling, G-protein–coupled receptors, semaphorin/plexin system) and physiological processes in cardiovascular functions, metabolism, and tumor metastasis. Department 3 (directed by Prof Didier Stainier) investigates questions related to vertebrate organogenesis including cell differentiation, tissue morphogenesis, organ homeostasis and function, and organ regeneration. Work in the department strongly relies on zebrafish as a model although other organisms such as the mouse are also used. Department IV (directed by Prof Werner Seeger) addresses diseases that affect the lung parenchyma, with a focus on its 3 functional compartments, the vascular, interstitial, and alveolar compartments. Particular attention is paid to the development of new treatment concepts, thereby shaping the translational focus of this Department. In addition to the 4 main departments, the institute hosts several independent research groups, which are financed by internal or competitive external funds (ERC [European Research Council], DFG [Deutsche Forschungsgemeinschaft], etc; Prof Nina Wettschureck, Rory Morty, Masanori Nakayama, Michael Potente, and Gergana Dobreva) and an external scientific member (Prof Christos Samakovlis). These independent research groups benefit tremendously from the outstanding scientific environment and state-of-the-art facilities at the institute, and in turn, the institute benefits greatly from the influx of bright young scientists who bring in new ideas and concepts.During the past decades, cutting-edge biomedical research has become strongly dependent on sophisticated techniques and advanced data processing. The MPI-HLR has, therefore, heavily invested into state-of-the-art core facilities, which provide researchers with top-quality technical support, thereby saving time, effort, and money to build up expertise in their own laboratories.Decisions affecting the institute as a whole including recruitment of new independent research groups are made by the board of directors, which consists of the heads of the 4 departments. Independent research group leaders are directly involved in all decisions ensuring maximum transparency and participation of junior scientists in the future of the institute. Daily business of the institute is coordinated by the managing director. This position rotates every 3 years among the different department heads, which ensures that active scientists endure the burden of administrative work only for a limited time and can otherwise fully concentrate on their scientific interests.The institute is reviewed every 2 to 3 years by its scientific advisory board consisting of leading experts in the field. Every 6 years, the MPS conducts a comparative evaluation to assure continued scientific excellence of its different institutes.Scientific Accomplishments: A Success StoryMax Planck researchers are able to develop long-term strategies or embark on innovative, risky projects because the core budget of established Max Planck directors is covered by institutional funds of the MPS. This strategic advantage has spectacularly paid off during the past decade with several landmark discoveries by MPI-HLR researchers. Productivity has particularly soared in the past 6 years resulting in 671 publications (Figure 2C), including 155 publications in top journals (impact factor >10), 12 reports were published in interdisciplinary journals such as Nature and Cell (42 publications in Nature family journal; 35 in Cell family journals; 125 publications in top journals such as CirculationResearch, Circulation, Journalof ClinicalInvestigation, eLife, Proceedings of the National Academy of Sciences of the United States of America, and others). Moreover, MPI-HLR contributed to 25 papers in top clinical journals (eg, New England Journal of Medicine, Lancet).Recent findings include identification of Oncostatin M as a major driver of cardiac dedifferentiation and remodeling. Oncostatin M induces dedifferentiation of cardiomyocytes, which then release signaling molecules to regulate trafficking of macrophages needed for remodeling and repair.1 Mesenchymal stem cells were found to follow and modulate inflammatory responses. MPI-HLR researchers detected that tumor cell–activated platelets induce opening of the endothelial barrier to allow transendothelial migration of tumor cells and that tumor cells stimulate endothelial cells to undergo necroptosis.2 Furthermore, FOXO1 was identified as an essential regulator of vascular growth by coupling metabolic and proliferative activities in endothelial cells.3 Basic principles and signaling pathways of angiogenesis and vascular homeostasis were disclosed, including, among others, Apelin, critical GPCR's (G-protein–coupled receptor), Notch signaling, the transcription factor Cloche, which had been enigmatic for ≈20 years, and epitranscriptomic regulation.4 The microRNAs miR-143/145 were identified as critical determinants of vascular smooth muscle cell maturation, and a new role of myostatin for regulation of metabolic processes in the heart was disclosed. Efficient revascularization of the injured area was noted to be essential in heart regeneration in zebrafish. Signaling mechanisms were discovered that drive lung fibrosis and pathological lung vascular inward remodeling underlying pulmonary hypertension.5 The latter findings were instrumental to establish novel sGC (soluble guanylate cyclase)-stimulator therapy in the clinical arena of pulmonary hypertension treatment.MPI-HLR researchers also made several seminal observations on the role of stem cells and morphogenetic pathways controlling stem cell fates6 and discovered a main regulator of cardiomyocyte-specific RNA splicing. In the developing heart, spatial differences in oxygenation were found to control cardiac progenitor cell expansion and cardiac morphogenesis via the HIF1α/Sirt1/Hes1 complex, preventing formation of congenital heart defects. Regarding physical stimuli, MPI-HLR researchers have demonstrated that the G-protein–coupled receptor P2Y2 and the cation channel PIEZO1 are key components of the mechanotransduction cascade initiated by blood flow over endothelial cells.Never Walk Alone: Networking and AlliancesThe MPI-HLR enjoys an enormous degree of scientific freedom and financial independence because of the continuous support by the MPS. Moreover, an esprit de corps has emerged, which is fostered and supported by numerous social networking events, which bring together all people working at the institute from senior PIs, postdocs, students, and technicians to animal care takers, administrative and technical maintenance staff, and visiting guests. Although the MPI-HLR is strong and large enough to be self-sufficient, it is never a good advice to walk alone. Therefore, the institute closely cooperates with several different partners not only for training of students but also as part of research alliances focusing on cardiovascular and lung diseases. The Excellence Cluster Cardiopulmonary System, funded via the Excellence Initiative of the German government, is a joint project between the MPI-HLR, the medical schools at the universities of Giessen and Frankfurt, and the Kerckhoff Hospital. Moreover, the institute plays a pivotal role in several research consortia sponsored by the state of Hesse and 2 newly founded national research centers, the German Center for Lung Research and the German Center for Cardiovascular Research. Furthermore, MPI-HLR researchers participate in numerous DFG Collaborative Research Centers, EU (European Union) programs, and other international collaborations. Formal research agreements were signed with the Biomedicine Research Institute in Buenos Aires/Argentina IBIOBA, the Guangzhou Institutes of Biomedicine and Health (GIBH) in Guangzhou, China, to establish the MPS-Chinese Academy Center for Regenerative Medicine, the Fundación Centro Nacional de Investigaciones Cardiovasculares in Madrid, Spain, and the International Institute for Molecular and Cellular Biology in Warsaw, Poland.Training the Next GenerationIdentification and training of the best and brightest minds is at the core of the MPS. The MPI-HLR has developed a comprehensive program to support basic and advanced training of students and junior researchers at 4 different levels: (1) Outreach to undergraduate students. (2) Training of PhD and MD students. All PhD and MD students are enrolled in a graduate program, the International Max Planck Research School for Heart and Lung Research (IMPRS-HLR), which was established in 2008. (3) Support for postdoctoral career development. (4) Mentoring program for junior PIs, who have just started independent research groups. During the past years, several junior group leaders have accepted tenured professorships in Germany or abroad, demonstrating that the MPI-HLR has found the right approach. In summary, top-quality research training has become a hallmark of the MPI-HLR, which has emerged as an ideal workplace for young, motivated researchers, who receive all possible support from more established colleagues.Future ChallengesAt present, the MPI-HLR is flowering, but a standstill means falling behind. This is why it is crucial, especially in the rapid pace of scientific discoveries, to prepare for future challenges. The MPI-HLR will continue to invest into additional research groups, which will require support from the MPS and external funding organizations. It is also of paramount importance to set the priorities right and identify or define newly emerging research areas. Basic research at the MPI-HLR will not be replaced by translational and clinical research but will be instrumental for innovative applied approaches, which will be realized by strengthening the alliance with the neighboring universities/medical schools.Sources of FundingResearch in the authors' laboratories is mainly funded by the Max Planck Society (MPS), the Deutsche Forschungsgemeinschaft (DFG), the Deutsches Zentrum for Herz- und Kreislaufforschung (DZHK), the Deutsches Zentrum für Lungenforschung (DZL), the European Research Council (ERC), and the Foundation Leducq.DisclosuresNone.FootnotesThe opinions expressed in News & Views are not necessarily those of the editors or of the American Heart Association.Correspondence to Thomas Braun, MD, PhD, Max Planck Institute for Heart and Lung Research Ludwigstr. 43, D-61231 Bad Nauheim, Germany. E-mail [email protected]References1. Lörchner H, Pöling J, Gajawada P, Hou Y, Polyakova V, Kostin S, Adrian-Segarra JM, Boettger T, Wietelmann A, Warnecke H, Richter M, Kubin T, Braun T. Myocardial healing requires Reg3β-dependent accumulation of macrophages in the ischemic heart.Nat Med. 2015; 21:353–362. doi: 10.1038/nm.3816.CrossrefMedlineGoogle Scholar2. Strilic B, Yang L, Albarrán-Juárez J, Wachsmuth L, Han K, Müller UC, Pasparakis M, Offermanns S. Tumour-cell-induced endothelial cell necroptosis via death receptor 6 promotes metastasis.Nature. 2016; 536:215–218. doi: 10.1038/nature19076.CrossrefMedlineGoogle Scholar3. Wilhelm K, Happel K, Eelen G, et al. FOXO1 couples metabolic activity and growth state in the vascular endothelium.Nature. 2016; 529:216–220. doi: 10.1038/nature16498.CrossrefMedlineGoogle Scholar4. Reischauer S, Stone OA, Villasenor A, et al. Cloche is a bHLH-PAS transcription factor that drives haemato-vascular specification.Nature. 2016; 535:294–298. doi: 10.1038/nature18614.CrossrefMedlineGoogle Scholar5. Savai R, Al-Tamari HM, Sedding D, Kojonazarov B, Muecke C, Teske R, Capecchi MR, Weissmann N, Grimminger F, Seeger W, Schermuly RT, Pullamsetti SS. Pro-proliferative and inflammatory signaling converge on FoxO1 transcription factor in pulmonary hypertension.Nat Med. 2014; 20:1289–1300. doi: 10.1038/nm.3695.CrossrefMedlineGoogle Scholar6. Caputo L, Witzel HR, Kolovos P, Cheedipudi S, Looso M, Mylona A, van IJcken WF, Laugwitz KL, Evans SM, Braun T, Soler E, Grosveld F, Dobreva G. The Isl1/Ldb1 complex orchestrates genome-wide chromatin organization to instruct differentiation of multipotent cardiac progenitors.Cell Stem Cell. 2015; 17:287–299. doi: 10.1016/j.stem.2015.08.007.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails April 28, 2017Vol 120, Issue 9 Advertisement Article InformationMetrics © 2017 American Heart Association, Inc.https://doi.org/10.1161/CIRCRESAHA.117.310763PMID: 28450360 Originally publishedApril 28, 2017 PDF download Advertisement SubjectsAnimal Models of Human DiseaseBasic Science ResearchMyocardial RegenerationTranslational StudiesVascular Biology