EXC 147:  Cardio-Pulmonary System

• Subject Area: Medicine
• Term: from 2006 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 24676099

• Final Report Year: 2019

Final Report Abstract

Heart and lung diseases are the leading causes of death and represent the highest socioeconomic burden of all diseases worldwide, with multiple interactions and largely unresolved treatment challenges. The Excellence Cluster Cardio-Pulmonary System (ECCPS), comprises the universities and medical hospitals of Frankfurt and Giessen and the Max-Planck Institute for Heart and Lung Research in Bad Nauheim, and was created as a Joint Research Centre to combine basic science approaches and bedside clinical research in the following research areas: • Stem/progenitor cells in cardio-pulmonary development, organ maintenance and regeneration • Vascular and cardiac remodelling processes and tailoring of reverse-remodelling therapy • Angiogenesis and alveogenesis in physiology, regeneration and repair • Matrix homeostasis and adaptive versus maladaptive mesenchymal responses in fibrosis • Redox-dependent signalling and interference strategies in hypoxia, ischemia and reoxygenation • Vascular and alveolar barrier integrity during inflammation and repair • The interface between the endocrine system, metabolism and the vasculature • The identification of biomarkers and molecular signatures for personalized medicine ECCPS scientists have made several ground-breaking contributions to these major areas in car-diopulmonary science. This is evidenced by top ranking publications in all of the dedicated research areas, the coordination of large national and international research consortia and - most importantly - the translation of several key findings into clinical use and exploitation. The latter is documented by successfully completed and ongoing phase II/III trials and filed patents. In ECCPS II, we have included several innovative aspects (e.g. epigenetics, metabolomics, in-vivo molecular imaging) in the existing research areas and have set up a novel international research area with the Imperial College London and global partners to combat the lung vascular diseases that represent major public health problems in resourcepoor areas of the world. In addition, we have established a sustainable technology platform that complements existing infrastructure and guarantees all of the ECCPS faculty access to cutting edge technology (e.g. bioinformatics of “omics”, high resolution imaging). Extending our efforts to support young scientists, we have established an ECCPS Academy, by combining the successful graduate programs set up in ECCPS I with postdoctoral and career development programs in basic and clinical cardiopulmonary research. These measures lent further support to the mission of the ECCPS, to decipher the molecular pathogenesis of and create tailored therapy for vascular and parenchymal heart and lung diseases.

Link to the final report

https://dx.doi.org/10.2314/KXP:1697279635

Publications

• Angiopoietin-2 sensitizes endothelial cells to TNF-α and has a crucial role in the induction of inflammation. Nat Med 12:235-39, 2006
  Fiedler U, Reiss Y, Scharpfenecker M, Grunow V, Koidl S, Thurston G, Gale NW, Witzenrath M, Rosseau S, Suttorp N, Sobke A, Herrmann M, Preissner KT, Vajkoczy P, Augustin HG
  
• Intracoronary bone marrow-derived progenitor cells in acute myocardial infarction. N Engl J Med 355:1210-21, 2006
  Schachinger V, Erbs S, Elsasser A, Haberbosch W, Hambrecht R, Holschermann H, Yu J, Corti R, Mathey DG, Hamm CW, Suselbeck T, Assmus B, Tonn T, Dimmeler S, Zeiher AM
  
• Transcoronary transplantation of progenitor cells after myocardial infarction. N Engl J Med 355:1222-32, 2006
  Assmus B, Honold J, Schachinger V, Britten MB, Fischer-Rasokat U, Lehmann R, Teupe C, Pistorius K, Martin H, Abolmaali ND, Tonn T, Dimmeler S, Zeiher AM
  
• Extracellular RNA constitutes a natural procoagulant cofactor in blood coagulation. Proc Natl Acad Sci USA 104:6388-93, 2007
  Kannemeier C, Shibamiya A, Nakazawa F, Trusheim H, Ruppert C, Markart P, Song Y, Tzima E, Kennerknecht E, Niepmann M, von Bruehl ML, Sedding D, Massberg S, Günther A, Engelmann B, Preissner KT
  
• SIRT1 controls endothelial angiogenic functions during vascular growth. Genes Dev 21:2644-58, 2007
  Potente M, Ghaeni L, Baldessari D, Mostoslavsky R, Rossig L, Dequiedt F, Haendeler J, Mione M, Dejana E, Alt FW, Zeiher AM, Dimmeler S
  
• Del-1, an endogenous leukocyte-endothelial adhesion inhibitor, limits inflame cell recruitment. Science 322:1101-4, 2008
  Choi EY, Chavakis E, Czabanka MA, Langer HF, Fraemohs L, Economopoulou M, Kundu RK, Orlandi A, Zheng YY, Prieto DA, Ballantyne CM, Constant SL, Aird WC, Papayannopoulou T, Gahmberg CG, Udey MC, Vajkoczy P, Quertermous T, Dimmeler S, Weber C, Chavakis T
  
• Efficient homing of multipotent adult mesenchymal stem cells depends on FROUNT–mediated clustering of CCR2. Cell Stem Cell 2:566-575, 2008
  Belema-Bedada F, Uchida S, Martire A, Kostin S, Braun T
  
• G12-G13-LARG-mediated signaling in vascular smooth muscle is required for saltinduced hypertension. Nat Med 14:64-68, 2008
  Wirth A, Benyó Z, Lukasova M, Leutgeb B, Wettschureck N, Gorbey S, Orsy P, Horváth B, Maser-Gluth C, Greiner E, Lemmer B, Schütz G, Gutkind JS, Offermanns S
  
• Lung epithelial apoptosis in influenza virus pneumonia: The role of macrophage expressed TNF- related apoptosis-inducing ligand. J Exp Med 205:3065-77, 2008
  Herold S, Steinmueller M, von Wulffen W, Cakarova L, Pinto R, Pleschka S, Mack M, Kuziel WA, Corazza N, Brunner T, Seeger W, Lohmeyer J
  
• Acquisition of the contractile phenotype of arterial smooth muscle cells depends on the miR- 143/145 gene cluster. J Clin Invest 119:2634-47, 2009
  Boettger T, Beetz N, Kostin S, Schneider J, Krüger M, Hein L, Braun T
  
• An inducible autoregulatory loop between HIPK2 and Siah2 at the apex of the hypoxic response. Nat Cell Biol 11:85-91, 2009
  Calzado MA, de la Vega L, Möller A, Bowtell DL, Schmitz ML
  
• Anaphylactic shock depends on endothelial Gq/G11. J Exp Med 206:411-20, 2009
  Korhonen H, Fisslthaler B, Moers A, Wirth A, Habermehl D, Wieland T, Schütz G, Wettschureck N, Fleming I, Offermanns S.
  
• Angiotensin II impairs endothelial function via tyrosine phosphorylation of the endothelial nitric oxide synthase. J Exp Med 206:2889-96, 2009
  Loot AE, Schreiber JG, Fisslthaler B, Fleming I
  
• Epidermal growth factor-like 7 (EGFL7) modulates Notch signaling and effects neural stem cell renewal. Nat Cell Biol 11:873-80, 2009
  Schmidt MHH, Bicker F, Nikolic I, Meister J, Babuke T, Piciric S, Muller-Esterl W, Plate KH, Dikic I
  
• MicroRNA-92a controls angiogenesis and functional recovery of ischemic tissues in mice. Science 324:1710-13, 2009
  Bonauer A, Carmona G, Iwasaki M, Mione M, Koyanagi M, Fischer A, Burchfield J, Fox H, Doebele C, Ohtani K, Chavakis E, Potente M, Tjwa M, Urbich C, Zeiher A, Dimmeler S
  
• Stress Doppler echocardiography in relatives of patients with idiopathic and familial pulmonary arterial hypertension: results of a multicenter European analysis of pulmonary artery pressure response to exercise and hypoxia. Circulation 119:1747-57, 2009
  Grünig E, Weissmann S, Ehlken N, Fijalkowska A, Fischer C, Fourme T, Galié N, Ghofrani HA, Harrison RE, Huez S, Humbert M, Janssen B, Kober J, Koehler R, Machado RD, Mereles D, Naeije R, Olschewski H, Provencher S, Reichenberger F, Retailleau K, Rocchi G, Simonneau G, Torbicki A, Trembath R, Seeger W
  
• WNT1-inducible signalling protein-1 mediates pulmonary fibrosis in mice and is upregulated in humans with idiopathic pulmonary fibrosis. J Clin Invest 119:772-87, 2009
  Königshoff M, Kramer M, Balsara N, Wilhelm J, Amarie OV, Jahn A, Rose F, Fink L, Seeger W, Schaefer L, Günther A, Eickelberg O
  
• An autocrine lactate loop mediates insulin-dependent inhibition of lipolysis through GPR81. Cell Metab 11:311-19, 2010
  Ahmed K, Tunaru S, Tang C, Müller M, Gille A, Sassmann A, Hanson J, Offermanns S
  
• EphrinB2 regulates VEGFR2 function in developmental and tumour angiogenesis. Nature 65:487-91, 2010
  Sawamiphak S, Seidel S, Essmann CL, Wilkinson GA, Pitulescu M, Acker T, Acker- Palmer A
  
• Epithelial stress and apoptosis underlie Hermansky-Pudlak syndrome associated interstitial pneumonia. Am J Respir Crit Care Med 182:207-219, 2010
  Mahavadi P, Korfei M, Henneke I, Liebisch G, Schmitz G, Gochuico BR, Markart P, Seeger W, Ruppert C, Günther A
  
• The proteoglycan biglycan regulates expression of the B cell chemoattractant CXCL13 and aggravates murine lupus nephritis. J Clin Invest 120:4251-72, 2010
  Moreth K, Brodbeck R, Babelova A, Gretz N, Spieker T, Zeng-Brouwers J, Pfeilschifter J, Young M, Schaefer RM, Schaefer L
  
• cAMP phosphordiesterase inhibitors increases nitric oxide production by modulating dimethylarginine dimethylaminohydrolases. Circulation 123:1194-204, 2011
  Pullamsetti SS, Savai R, Schaefer MB, Wilhelm J, Ghofrani HA, Weissmann N, Schudt C, Fleming I, Mayer K, Leiper J, Seeger W, Grimminger F, Schermuly RT
  
• Inducible NOS inhibition reverses tobacco-smoke-induced emphysema and pulmonary hypertension in mice. Cell 147:293-305, 2011
  Seimetz M, Parajuli N, Pichl A, Veit F, Kwapiszewska G, Weisel FC, Milger K, Egemnazarov B, Turowska A, Fuchs B, Nikam S, Roth M, Sydykov A, Medebach T, Klepetko W, Jaksch P, Dumitrascu R, Garn H, Voswinckel R, Kostin S, Seeger W, Schermuly RT, Grimminger F, Ghofrani HA, Weissmann N
  
• Jumonji domain-containing protein 6 (Jmjd6) is required for angiogenic sprouting and regulates splicing of VEGF-receptor 1. Proc Natl Acad Sci USA 108:3276-81, 2011
  Boeckel JN, Guarani V, Koyanagi M, Röxe T, Lengeling A, Schermuly TR, Gellet P, Braun T, Zeiher A, Dimmeler S
  
• Lung endothelial monocyte-activating protein 2 is a mediator of cigarette smoke-induced emphysema in mice. J Clin Invest 121:2470-9, 2011
  Clauss M, Voswinckel R, Rajashekhar G, Sigua NL, Fehrenbach H, Rush NI, Schweitzer KS, Yildirim AÖ, Kamocki K, Fisher AJ, Gu Y, Safadi B, Nikam S, Hubbard WC, Tuder RM, Twigg HL 3rd, Presson RG, Sethi S, Petrache I
  
• MicroRNA-29 in aortic dilation: implications for aneurysm formation. Circ Res 109:1115-1119, 2011
  Boon RA, Seeger T, Heydt S, Fischer A, Hergenreider E, Horrevoets AJ, Vinciguerra M, Rosenthal N, Sciacca S, Pilato M, van Heijningen P, Essers J, Brandes RP, Zeiher AM, Dimmeler S
  
• Oncostatin M is a major mediator of cardiomyocyte dedifferentiation and remodeling. Cell Stem Cell 9:420-32, 2011
  Kubin T, Poling J, Kostin S, Gajawada P, Hein S, Rees W, Wietelmann A, Tanaka M, Lorchner H, Schimanski S, Szibor M, Warnecke H and Braun T
  
• Transcoronary concentration gradients of circulating microRNAs. Circulation 124:1936-44, 2011
  De Rosa S, Fichtlscherer S, Lehmann R, Assmus B, Dimmeler S, Zeiher AM
  
• A redox-regulated SUMO/acetylation switch of HIPK2 controls the survival threshold to oxidative stress. Mol Cell 46:472-483, 2012
  De la Vega L, Grishina I, Moreno R, Krüger M, Braun T, Schmitz ML
  
• Acetylation-dependent regulation of endothelial Notch signalling by the SIRT1 deacetylase. Nature 473: 234-8, 2011
  Guarani V, Deflorian G, Franco CA, Kruger M, Phng LK, Bentley K, Toussaint L, Dequiedt F, Mostoslavsky R, Schmidt MH, Zimmermann B, Brandes RP, Mione M, Westphal CH, Braun T, Zeiher AM, Gerhardt H, Dimmeler S, Potente M
  
• Acute myocardial infarction activates progenitor cells and increases Wnt signaling in the bone marrow. Eur Heart J 33:1911-1919, 2012
  Assmus B, Iwasaki M, Schächinger V, Roexe T, Koyanagi M, Iekushi K, Xu Q, Tonn T, Seifried E, Liebner S, Kranert WT, Grünwald F, Dimmeler S, Zeiher AM
  
• Alveolar epithelial cells orchestrate DC function in murine viral pneumonia. J Clin Invest 122:3652-3664, 2012
  Unkel B, Hoegner K, Clausen BE, Lewe-Schlosser P, Bodner J, Gattenloehner S, Janssen H, Seeger W, Lohmeyer J, Herold S
  
• Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs. Nature Cell Biol 14:249-256, 2012
  Hergenreider E, Heydt S, Treguer K, Boettger T, Horrevoets AJ, Zeiher AM, Scheffer MP, Frangakis AS, Yin X, Mayr M, Braun T, Urbich C, Boon RA, Dimmeler S
  
• Immune and inflammatory cell involvement in the pathology of idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med 186:897-908, 2012
  Savai R, Pullamsetti SS, Kolbe J, Bieniek E, Voswinckel R, Fink L, Scheed A, Ritter C, Dahal BK, Vater A, Klussmann S, Ghofrani HA, Weissmann N, Klepetko W, Banat GA, Seeger W, Grimminger F, Schermuly RT
  
• Nox4 is a protective reactive oxygen species generating vascular NADPH oxidase. Circ Res 110:1217-1225, 2012
  Schröder K, Zhang M, Benkhoff S, Mieth A, Pliquett R, Kosowski J, Kruse C, Luedike P, Michaelis UR, Weissmann N, Dimmeler S, Shah AM, Brandes RP
  
• Procontractile G protein-mediated signaling pathways antagonistically regulate smooth muscle differentiation in vascular remodeling. J Exp Med 209:2277-2290, 2012
  Althoff TF, Juarez JA, Troidl K, Tang C, Wang S, Wirth A, Takefuji M, Wettschureck N, Offermanns S
  
• Regulation of cardiac microRNAs by bone marrow mononuclear cell therapy in myocardial infarction. Circulation 125:1765-73, 2012
  Iekushi K, Seeger F, Assmus B, Zeiher AM, Dimmeler S
  
• Classical transient receptor potential channel 1 in hypoxia-induced pulmonary hypertension. Am J Respir Crit Care Med 188: 1451-1459, 2013
  Malczyk M, Veith C, Fuchs B, Hofmann K, Storch U, Schermuly RT, Witzenrath M, Ahlbrecht K, Fecher-Trost C, Flockerzi V, Ghofrani HA, Grimminger F, Seeger W, Gudermann T, Dietrich A, Weissmann N
  
• Effect of shock wave-facilitated intracoronary cell therapy on LVEF in patients with chronic heart failure: the CELL- WAVE randomized clinical trial. J Am Med Assoc 309:1622-1631, 2013
  Assmus B, Walter DH, Seeger FH, Leistner DM, Steiner J, Ziegler I, Lutz A, Khaled W, Klotsche J, Tonn T, Dimmeler S, Zeiher AM
  
• G13 controls angiogenesis through regulation of VEGFR-2 expression. Dev Cell 25:427-434, 2013
  Sivaraj KK, Takefuji M, Schmidt I, Adams RH, Offermanns S, Wettschureck N
  
• Imatinib mesylate as add-on therapy for pulmonary arterial hypertension: results of the randomized IMPRES study. Circulation 127:1128-1138, 2013
  Hoeper MM, Barst RJ, Bourge RC, Feldman J, Frost AE, Galié N, Gómez-Sánchez MA, Grimminger F, Grünig E, Hassoun PM, Morrell NW, Peacock AJ, Satoh T, Simonneau G, Tapson VF, Torres F, Lawrence D, Quinn DA, Ghofrani HA
  
• Inhibition of microRNA-92a protects against ischemia/reperfusion injury in a large-animal model. Circulation 128:1066-1075, 2013
  Hinkel R, Penzkofer D, Zühlke S, Fischer A, Husada W, Xu QF, Baloch E, van Rooij E, Zeiher AM, Kupatt C, Dimmeler S
  
• Macrophage-expressed IFN-beta contributes to apoptotic alveolar epithelial cell injury in severe influenza virus pneumonia. PLoS Pathog 9:e1003188, 2013
  Hogner K, Wolff T, Pleschka S, Plog S, Gruber AD, Kalinke U, Walmrath HD, Bodner J, Gattenlohner S, Lewe-Schlosser P, Matrosovich M, Seeger W, Lohmeyer J, Herold S
  
• MicroRNA-223 antagonizes angiogenesis by targeting β1 integrin and preventing growth factor signaling in endothelial cells. Circ Res 113:1320-1330, 2013
  Shi L, Fisslthaler B, Zippel N, Frömel T, Hu J, Elgheznawy A, Heide H, Popp R, Fleming I
  
• MicroRNA-34a regulates cardiac ageing and function. Nature 495:107-110, 2013
  Boon RA, Iekushi K, Lechner S, Seeger T, Fischer A, Heydt S, Kalua D, Treguer K, Carmona G, Bonauer A, Horrevoets AJ, Didler N, Girmatsion Z, Biliczki P, Ehrlich JR, Katus HA, Müller OJ, Potente M, Zeiher AM, Dimmeler S
  
• Myf5-positive satellite cells contribute to Pax7-dependent long-term maintenance of adult muscle stem cells. Cell Stem Cell 13:590-601, 2013
  Günther S, Kim, J, Kostin S, Leppe, C Fan CM, Braun T
  
• NADPH oxidase 4 limits bone mass by promoting osteoclastogenesis. J Clin Invest. 123:4731-4738, 2013
  Goettsch C, Babelova A, Trummer O, Erben RG, Rauner M, Rammelt S, Weissmann N, Weinberger V, Benkhoff S, Kampschulte M, Obermayer-Pietsch B, Hofbauer LC, Brandes RP, Schröder K
  
• Platelet-derived nucleotides promote tumor-cell transendothelial migration and metastasis via P2Y2 receptor. Cancer Cell 24:130-137, 2013
  Schumacher D, Strilic B, Sivaraj KK, Wettschureck N, Offermanns S
  
• RhoGEF12 controls cardiac remodeling by integrating G-protein- and integrin-dependent signaling cascades. J Exp Med 210: 665-673, 2013
  Takefuji M Krüger M, Sivaraj KK, Kaibuchi K, Offermanns S, Wettschureck N
  
• Riociguat for the treatment of chronic thromboembolic pulmonary hypertension. N Engl J Med 369:319-329, 2013
  Ghofrani HA, D'Armini AM, Grimminger F, Hoeper MM, Jansa P, Kim NH, Mayer E, Simonneau G, Wilkins MR, Fritsch A, Neuser D, Weimann G, Wang C, CHEST-1 Study Group
  
• Riociguat for the treatment of pulmonary arterial hypertension. N Engl J Med 369:330-340, 2013
  Ghofrani HA, Galie N, Grimminger F, Grunig E, Humbert M, Jing ZC, Keogh AM, Langleben D, Kilama MO, Fritsch A, Neuser D, Rubin LJ, PATENT-1 Study Group
  
• The polarity protein Scrib is essential for directed endothelial cell migration. Circ Res 112:924-934, 2013
  Michaelis UR, Chavakis E, Kruse C, Jungblut B, Kaluza D, Wandzioch K, Manavski Y, Heide H, Santoni MJ, Potente M, Eble JA, Borg JP, Brandes RP
  
• glia cells regulate Notch signaling and retinal angiogenesis via the generation of 19,20-dihydroxydocosapentaenoic acid. J Exp Med 211:281-295, 2014
  Hu J, Popp R, Frömel T, Ehling M, Awwad K, Adams RH, Hammes HP, Fleming I. Müller
  
• Inhaled granulocyte/macrophage colony-stimulating factor as treatment of pneumonia-associated acute respiratory distress syndrome. Am J Respir Crit Care Med 189:609-611, 2014
  Herold S, Hoegner K, Vadasz I, Gessler T, Wilhelm J, Mayer K, Morty RE, Walmrath HD, Seeger W, Lohmeyer J
  
• Long-term clinical outcome after intracoronary application of bone marrow-derived mononuclear cells for acute myocardial infarction: Migratory capacity of administered cells determines event-free survival. Eur Heart J 35:1275-1283, 2014
  Assmus B, Leistner DM, Schächinger V, Erbs S, Elsässer A, Haberbosch W, Hambrecht R, Sedding D, Yu J, Corti R, Mathey DG, Barth C, Mayer-Wehrstein C, Burck I, Sueselbeck T, Dill T, Hamm CW, Tonn T, Dimmeler S, Zeiher AM
  
• Prehospital ticagrelor in ST-segment elevation myocardial infarction. N Engl J Med. 371:1016-27, 2014
  Montalescot G, van 't Hof AW, Lapostolle F, Silvain J, Lassen JF, Bolognese L, Cantor WJ, Cequier A, Chettibi M, Goodman SG, Hammett CJ, Huber K, Janzon M, Merkely B, Storey RF, Zeymer U, Stibbe O, Ecollan P, Heutz WM, Swahn E, Collet JP, Willems FF, Baradat C, Licour M, Tsatsaris A, Vicaut E, Hamm CW; ATLANTIC Investigators
  
• Proproliferative and inflammatory signaling converge on FoxO1 transcription factor in pulmonary hypertension. Nature Med 20:1289-1300, 2014
  Savai R, Al-Tamari HM, Sedding D, Kojonazarov B, Muecke C, Teske R, Capecchi MR, Weissmann N, Grimminger F, Seeger W, Schermuly RT, Pullamsetti S
  
• RBM24 is a major regulator of muscle-specific alternative splicing. Dev Cell 31:87-99, 2014
  Yang J, Hung L-H, Licht T, Kostin S, Looso M, Khrameeva E, Bindereif A, Schneider A, Braun T
  
• Stimulation of soluble guanylate cyclase prevents cigarette smoke-induced pulmonary hypertension and emphysema. Am J Respir Crit Care Med 189: 1359-1373, 2014
  Weissmann N, Lobo B, Pichl A, Parajuli N, Seimetz M, Puig-Pey R, Ferrer E, Peinado VI, Domínguez-Fandos D, Fysikopoulos A, Stasch JP, Ghofrani HA, Coll-Bonfill N, Frey R, Schermuly RT, García-Lucio J, Blanco I, Bednorz M, Tura-Ceide O, Tadele E, Brandes RP, Grimminger J, Klepetko W, Jaksch P, Rodriguez-Roisin R, Seeger W, Grimminger F, Barberà JA
  
• The long noncoding RNA MALAT1 regulates endothelial cell function and vessel growth. Circ Res 114:1389-1397, 2014
  Michalik KM, You X, Manavski Y, Doddaballapur A, Zörnig M, Braun T, John D, Ponomareva Y, Chen W, Uchida S, Boon RA, Dimmeler S
  
• Vitamin D promotes vascular regeneration. Circulation 130:976-986, 2014
  Wong MS, Leisegang MS, Kruse C, Vogel J, Schürmann C, Dehne N, Weigert A, Herrmann E, Brüne B, Shah AM, Steinhilber D, Offermanns S, Carmeliet G, Badenhoop K, Schröder K, Brandes RP
  
• Dicer cleavage by calpain determines platelet microRNA levels and function in diabetes. Circ Res 117:157-165, 2015
  Elgheznawy A, Shi L, Hu J, Wittig I, Laban H, Pircher J, Mann A, Provost P, Randriamboavonjy V, Fleming I
  
• Genetic compensation induced by deleterious mutations but not gene knockdowns. Nature 524:230-233, 2015
  Rossi A, Kontarakis Z, Gerri C, Nolte H, Holper S, Kruger M, Stainier DY
  
• Intraindividual response to treatment with pirfenidone in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 191:110-3, 2015
  Loeh B, Drakopanagiotakis F, Bandelli GP, von der Beck D, Tello S, Cordani E, Rizza E, Barrocu L, Markart P, Seeger W, Guenther A, Albera C
  
• Loss of FFA2 and FFA3 increases insulin secretion and improves glucose tolerance in type 2 diabetes. Nat Med 21: 173-177, 2015
  Tang C, Ahmed K, Gille A, Lu S, Gröne HJ, Tunaru S, Offermanns S
  
• Macrophage and cancer cell cross-talk via CCR2 and CX3CR1 is a fundamental mechanism driving lung cancer. Am J Respir Crit Care Med 191:437-447, 2015
  Schmall A, Al-Tamari HM, Herold S, Kampschulte M, Weigert A, Wietelmann A, Vipotnik N, Grimminger F, Seeger W, Pullamsetti SS, Savai R
  
• Myocardial healing requires Reg3beta-dependent accumulation of macrophages in the ischemic heart. Nature Med 21:353-362, 2015
  Lorchner H, Poling J, Gajawada P, Hou Y, Polyakova V, Kostin S, Adrian-Segarra JM, Boettger T, Wietelmann A, Warnecke H, Richter M, Kubin T, Braun T
  
• Regulation of endoplasmic reticulum turnover by selective autophagy. Nature 522:354-358, 2015
  Khaminets A, Heinrich T, Mari M, Grumati P, Huebner AK, Akutsu M, Liebmann L, Stolz A, Nietzsche S, Koch N, Mauthe M, Kalona I, Qualmann B, Weis J, Reggiori F, Kurth I, Hübner CA, Dikic I
  
• The intersection of the extrinsic hedgehog and WNT/Wingless signals with the intrinsic Hox code underpins branching pattern and tube shape diversity in the drosophila airways. PLoS Genet 11:e1004929, 2015
  Matsuda R, Hosono C, Saigo K, Samakovlis C
  
• The Isl1/Ldb1 complex orchestrates genome-wide chromatin organization to instruct differentiation of multipotent cardiac progenitors. Cell Stem Cell 17:287-299, 2015
  Caputo L, Witzel HR, Kolovos P, Cheedipudi S, Looso M, Mylona A, van IJcken WF, Laugwitz KL, Evans SM, Braun T, Soler E, Grosveld P, Dobreva G
  
• The NADPH oxidase Nox4 has antiatherosclerotic functions. Eur Heart J 36:3447-3456, 2015
  Schürmann C, Rezende F, Kruse C, Yasar Y, Löwe O, Fork C, van de Sluis B, Bremer R, Weissmann N, Shah AM, Jo H, Brandes RP, Schröder K
  
• Transient junction anisotropies orient annular cell polarization in the Drosophila airway tubes. Nat Cell Biol 17:1569-1576, 2015
  Hosono C, Matsuda R, Adryan B, Samakovlis C
  
• Adenosine-to-inosine RNA editing controls cathepsin S expression in atherosclerosis by enabling HuR-mediated posttranscriptional regulation. Nature Med 22:1140-1150, 2016
  Stellos K, Gatsiou A, Stamatelopoulos K, Perisic Matic L, John D, Lunella FF, Jae N, Rossbach O, Amrhein C, Sigala F, Boon RA, Fürtig B, Manavski Y, You X, Uchida S, Keller T, Boeckel JN, Franco-Cereceda A, Chen W, Schwalbe H, Bindereif A, Eriksson P, Hedin U, Zeiher AM, Dimmeler S
  
• Cloche is a bHLH-PAS transcription factor that drives haematovascular specification. Nature 535:294-298, 2016
  Reischauer S, Stone OA, Villasenor A, Chi N, Jin SW, Martin M, Lee MT, Fukuda N, Marass M, Witty A, Fiddes I, Kuo T, Chung WS, Salek S, Lerrigo R, Alsiö J, Luo S, Tworus D, Augustine SM, Mucenieks S, Nystedt B, Giraldez AJ, Schroth GP, Andersson O, Stainier DY
  
• Endothelial cation channel PIEZO1 controls blood pressure by mediating flow-induced ATP release. J Clin Invest 126:4527-4536, 2016
  Wang S, Chennupati R, Kaur H, Iring A, Wettschureck N, Offermanns S
  
• FOXO1 couples metabolic activity and growth state in the vascular endothelium. Nature 529:216-220, 2016
  Wilhelm K, Happel K, Eelen G, Schoors S, Oellerich MF, Lim R, Zimmermann B, Aspalter IM, Franco CA, Boettger T, Braun T, Fruttiger M, Rajewsky K, Keller C, Brüning JC, Gerhardt H, Carmeliet P, Potente M
  
• Macrophage-epithelial paracrine crosstalk inhibits lung edema clearance during influenza infection. J Clin Invest 126:1566-1580, 2016
  Peteranderl C, Morales-Nebreda L, Selvakumar B, Lecuona E, Vadasz I, Morty RE, Schmoldt C, Bespalowa J, Wolff T, Pleschka S, Mayer K, Gattenloehner S, Fink L, Lohmeyer J, Seeger W, Sznajder JI, Mutlu GM, Budinger GR, Herold S
  
• Phosphoribosylation of ubiquitin promotes serine ubiquitination and impairs conventional ubiquitination. Cell 167:1636-1649, 2016
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