EXC 229:  Zelluläre Stressantworten bei Alters-assoziierten Erkrankungen

• Fachliche Zuordnung: Medizin
• Förderung: Förderung von 2007 bis 2018
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 39010820

• Erstellungsjahr: 2020

Zusammenfassung der Projektergebnisse

Der demografische Wandel moderner westlicher Gesellschaften, mit ständig steigenden Lebenserwartungen und dem damit verbundenen erhöhten Risiko für altersassoziierte Krankheiten wie z.B. Diabetes, Fettleibigkeit, Haut-, Nieren- oder neurodegenerativen Erkrankungen, stellen für den Einzelnen und die Gesellschaft eine enorme Herausforderung dar. Die Entdeckung, dass durch Modifizierung definierter Signalwege die Lebensspanne verlängert und gleichzeitig das Auftreten altersassoziierter Krankheiten verzögert werden kann, bildet die Basis für die wissenschaftliche Mission des Kölner Exzellenzclusters CECAD in dem molekulare und zelluläre Mechanismen des Alterns aufgeklärt werden, um neue Ansätze für Prävention, Diagnose und Behandlung altersassoziierter Krankheiten zu definieren. CECAD hat dazu aktiv herausragende Grundlagenwissenschaftler*innen und Kliniker*innen rekrutiert, die im Verbund an der Universität zu Köln (UoC), den Max-Planck-Instituten für Biologie des Alterns (MPI AGE) und für Stoffwechselforschung (MPI MR) und dem Deutschen Zentrum für neurodegenerative Erkrankungen (DZNE) arbeiten. Darüber hinaus hat CECAD zusammen mit der Universität zu Köln massive infrastrukturelle Veränderungen vorgenommen, die CECAD als eines der weltweit führenden Zentren der Alternsforschung etabliert haben. Durch eine zielgerichtete Rekrutierungsstrategie wurde ein internationales und integratives Forschungsumfeld mit einem hohen Anteil von Wissenschaftler*innen geschaffen. Parallel dazu wurden Bildungsmaßnahmen aufgebaut, um die weltweit besten wissenschaftlichen Talente auf allen akademischen Ebenen besser auszubilden. Insgesamt haben all diese Entwicklungen zu einer intensiven Zusammenarbeit der Wissenschaftler*innen und einem raschen Anstieg der Forschungsdynamik geführt, die es ermöglicht haben, neuartige Grundprinzipien für das Altern und altersassoziierte Krankheiten aufzudecken und potenzielle neue Interventionsziele zu identifizieren. Während sich die Arbeiten zunächst auf die Definition der Rolle zellautonomer Qualitätskontrollmechanismen beim Altern und bei altersassoziierten Krankheiten konzentrierten, zeigen neue Erkenntnisse aus der zweiten Periode, dass zellautonome Mechanismen entscheidend durch die wechselseitige Kommunikation zwischen verschiedenen Organismen und durch Signale aus der Umwelt beeinflusst werden und so Langlebigkeit und Gesundheit kontrollieren, was neue Ansatzpunkte für therapeutische Optionen eröffnet. Daher wird CECAD zukünftig sein Forschungsprogramm erweitern und Kernstrukturen und Bildungsprogramme in diesen Bereichen unterstützen, während gleichzeitig seine Translationsstudien durch den Einbezug einzigartiger Patientenkohortendaten verbessert werden. Zusammengenommen werden diese Bemühungen aller am CECAD beteiligten PIs und Institutionen es ermöglichen, CECADs führende Rolle in der internationalen Alterungsforschung und als Ausbildungsort für Alternsforscher auf allen akademischen Ebenen zu festigen und auszubauen.

Link zum Abschlussbericht

https://dx.doi.org/10.2314/GBV:1697037887

Projektbezogene Publikationen (Auswahl)

• (2011) CDC-48/p97 coordinates CDT-1 degradation with GINS chromatin dissociation to ensure faithful DNA replication. Mol Cell, Volume 44, 1, 7 October 2011: 85-96
  Franz A, Orth M, Pirson P, Sonneville R, Blow J, Gartner A, Stemmann O, Hoppe T
  
• (2008) C. elegans dauer formation and the molecular basis of plasticity. Genes Dev 22: 2149-65
  Fielenbach N, Antebi A
  
• (2008) Endothelial cell-specific NF-kappaB inhibition protects mice from atherosclerosis. Cell Metab 8: 372-83
  Gareus R, Kotsaki E, Xanthoulea S, van der Made I, Gijbels MJ, Kardakaris R, Polykratis A, Kollias G, de Winther MP, Pasparakis M
  
• (2008) Epidermal insulin/IGF-1 signalling control interfollicular morphogenesis and proliferative potential through Rac activation. EMBO J 27: 2091-101
  Stachelscheid H, Ibrahim H, Koch L, Schmitz A, Tscharntke M, Wunderlich FT, Scott J, Michels C, Wickenhauser C, Haase I, Brüning JC, Niessen CM
  
• (2008) Function of TRADD in tumor necrosis factor receptor 1 signaling and in TRIF-dependent inflammatory responses. Nat Immunol 9: 1037-46
  Ermolaeva MA, Michallet MC, Papadopoulou N, Utermohlen O, Kranidioti K, Kollias G, Tschopp J, Pasparakis M
  
• (2008) Prohibitins control cell proliferation and apoptosis by regulating OPA1-dependent cristae morphogenesis in mitochondria. Genes Dev 22: 476-88
  Merkwirth C, Dargazanli S, Tatsuta T, Geimer S, Lower B, Wunderlich FT, von Kleist-Retzow JC, Waisman A, Westermann B, Langer T
  
• (2009) Acid sphingomyelinase is a key regulator of cytotoxic granule secretion by primary T lymphocytes. Nat Immunol 10: 761-8
  Herz J, Pardo J, Kashkar H, Schramm M, Kuzmenkina E, Bos E, Wiegmann K, Wallich R, Peters PJ, Herzig S, Schmelzer E, Krönke M, Simon MM, Utermohlen O
  
• (2009) Amino-acid imbalance explains extension of lifespan by dietary restriction in Drosophila. Nature 462: 1061-4
  Grandison RC, Piper MD, Partridge L
  
• (2009) An intersubunit signaling network coordinates ATP hydrolysis by m-AAA proteases. Mol Cell 35: 574-85
  Augustin S, Gerdes F, Lee S, Tsai FT, Langer T, Tatsuta T
  
• (2009) Identification of a putative lysosomal cobalamin exporter altered in the cblF defect of vitamin B12 metabolism. Nat Genet 41: 234-9
  Rutsch F, Gailus S, Miousse IR, Suormala T, Sagne C, Toliat MR, Nürnberg G, Wittkampf T, Buers I, Sharifi A, Stucki M, Becker C, Baumgartner M, Robenek H, Marquardt T, Hohne W, Gasnier B, Rosenblatt DS, Fowler B, Nürnberg P
  
• (2009) Inactivation of the Fto gene protects from obesity. Nature 458: 894-8
  Fischer J, Koch L, Emmerling C, Vierkotten J, Peters T, Brüning JC, Ruther U
  
• (2009) Methylation of 12S rRNA is necessary for in vivo stability of the small subunit of the mammalian mitochondrial ribosome. Cell Metab 9: 386-97
  Metodiev MD, Lesko N, Park CB, Camara Y, Shi Y, Wibom R, Hultenby K, Gustafsson CM, Larsson NG
  
• (2009) Nuclear hormone receptor regulation of microRNAs controls developmental progression. Science 324: 95-8
  Bethke A, Fielenbach N, Wang Z, Mangelsdorf DJ, Antebi A
  
• (2009) Persistent transcription-blocking HAT lesions trigger somatic growth attenuation associated with longevity. Nat Cell Biol 11: 604-15
  Garinis GA, Uittenboogaard LM, Stachelscheid H, Fousteri M, van Ijcken W, Breit TM, van Steeg H, Mullenders LH, van der Horst GT, Brüning JC, Niessen CM, Hoeijmakers JH, Schumacher B
  
• (2009) Random point mutations with major effects on protein-coding genes are the driving force behind premature aging in mtDNA mutator mice. Cell Metab 10: 131-8
  Edgar D, Shabalina I, Camara Y, Wredenberg A, Calvaruso MA, Nijtmans L, Nedergaard J, Cannon B, Larsson NG, Trifunovic A
  
• (2009) Riboflavin kinase couples TNF receptor 1 to NADPH oxidase. Nature 460: 1159-63
  Yazdanpanah B, Wiegmann K, Tchikov V, Krut O, Pongratz C, Schramm M, Kleinridders A, Wunderlich T, Kashkar H, Utermohlen O, Brüning JC, Schutze S, Krönke M
  
• (2009) The genetic interactome of prohibitins: coordinated control of cardiolipin and phosphatidylethanolamine by conserved regulators in mitochondria. J Cell Biol 184: 583-96
  Osman C, Haag M, Potting C, Rodenfels J, Dip PV, Wieland FT, Brugger B, Westermann B, Langer T
  
• (2010) Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet 376: 1164-74
  Hallek M, Fischer K, Fingerle-Rowson G, Fink AM, Busch R, Mayer J, Hensel M, Hopfinger G, Hess G, von Grünhagen U, Bergmann M, Catalano J, Zinzani PL, Caligaris-Cappio F, Seymour JF, Berrebi A, Jäger U, Cazin B, Trneny M, Westermann A, Wendtner CM, Eichhorst BF, Staib P, Bühler A, Winkler D, Zenz T, Böttcher S, Ritgen M, Mendila M, Kneba M, Döhner H, Stilgenbauer S; International Group of Investigators; German Chronic Lymphocytic Leukaemia Study Group
  
• (2010) Mechanisms of life span extension by rapamycin in the fruit fly Drosophila melanogaster. Cell Metab 11: 35-46
  Bjedov I, Toivonen JM, Kerr F, Slack C, Jacobson J, Foley A, Partridge L
  
• (2011) CEP152 is a genome maintenance protein disrupted in Seckel syndrome. Nat Genet 43: 23-6
  Kalay E, Yigit G, Aslan Y, Brown KE, Pohl E, Bicknell LS, Kayserili H, Li Y, Tuysuz B, Nürnberg G, Kiess W, Koegl M, Baessmann I, Buruk K, Toraman B, Kayipmaz S, Kul S, Ikbal M, Turner DJ, Taylor MS, Aerts J, Scott C, Milstein K, Dollfus H, Wieczorek D, Brunner HG, Hurles M, Jackson AP, Rauch A, Nürnberg P, Karaguzel A, Wollnik B
  
• (2011) FADD prevents RIP3-mediated epithelial cell necrosis and chronic intestinal inflammation. Nature 477: 330-4
  Welz PS, Wullaert A, Vlantis K, Kondylis V, Fernandez-Majada V, Ermolaeva M, Kirsch P, Sterner-Kock A, van Loo G, Pasparakis M
  
• (2011) High-fat feeding promotes obesity via insulin receptor/PI3K-dependent inhibition of SF-1 VMH neurons. Nat Neurosci 14: 911-8
  Klöckener T, Hess S, Belgardt BF, Paeger L, Verhagen LA, Husch A, Sohn JW, Hampel B, Dhillon H, Zigman JM, Lowell BB, Williams KW, Elmquist JK, Horvath TL, Kloppenburg P, Brüning JC
  
• (2011) MTERF4 regulates translation by targeting the methyltransferase NSUN4 to the mammalian mitochondrial ribosome. Cell Metab 13: 527-39
  Camara Y, Asin-Cayuela J, Park CB, Metodiev MD, Shi Y, Ruzzenente B, Kukat C, Habermann B, Wibom R, Hultenby K, Franz T, Erdjument-Bromage H, Tempst P, Hallberg BM, Gustafsson CM, Larsson NG
  
• (2011) Obesity-induced over-expression of miRNA-143 inhibits insulin-stimulated AKT activation and impairs glucose metabo- lism. Nat Cell Biol 13: 434-46
  Jordan SD, Kruger M, Willmes DM, Redemann N, Wunderlich FT, Bronneke HS, Merkwirth C, Kashkar H, Olkkonen VM, Bottger T, Braun T, Seibler J, Brüning JC
  
• (2011) Role for insulin signaling in catecholaminergic neurons in control of energy homeostasis. Cell Metab 13: 720-8
  Könner AC, Hess S, Tovar S, Mesaros A, Sánchez-Lasheras C, Evers N, Verhagen LA, Brönneke HS, Kleinridders A, Hampel B, Kloppenburg P, Brüning JC
  
• (2011) The Machado-Joseph disease deubiquitylase ATX-3 couples longevity and proteostasis. Nat Cell Biol 13: 273-81
  Kuhlbrodt K, Janiesch PC, Kevei E, Segref A, Barikbin R, Hoppe T
  
• (2012) A steroid receptor-microRNA switch regulates life span in response to signals from the gonad. Science 338: 1472-6
  Shen Y, Wollam J, Magner D, Karalay O, Antebi A
  
• (2012) Intramitochondrial transport of phosphatidic acid in yeast by a lipid transfer protein. Science 338: 815-8
  Connerth M, Tatsuta T, Haag M, Klecker T, Westermann B, Langer T
  
• (2013) aPKClambda controls epidermal homeostasis and stem cell fate through regulation of division orientation. J Cell Biol 202: 887-900
  Niessen MT, Scott J, Zielinski JG, Vorhagen S, Sotiropoulou PA, Blanpain C, Leitges M, Niessen CM
  
• (2013) DNA damage in germ cells induces an innate immune response that triggers systemic stress resistance. Nature 501: 416-20
  Ermolaeva MA, Segref A, Dakhovnik A, Ou HL, Schneider JI, Utermohlen O, Hoppe T, Schumacher B
  
• (2013) Insulin/IGF-1 controls epidermal morphogenesis via regulation of FoxO-mediated p63 inhibition. Dev Cell 26: 176-87
  Günschmann C, Stachelscheid H, Akyuz MD, Schmitz A, Missero C, Brüning JC, Niessen CM
  
• (2013) Mitochondrial dynamics controlled by mitofusins regulate Agrp neuronal activity and diet-induced obesity. Cell 155: 188-99
  Dietrich MO, Liu ZW, Horvath TL
  
• (2013) Obesity-induced overexpression of miR-802 impairs glucose metabolism through silencing of Hnf1b. Nature 494: 111-5
  Kornfeld JW, Baitzel C, Konner AC, Nicholls HAT, Vogt MC, Herrmanns K, Scheja L, Haumaitre C, Wolf AM, Knippschild U, Seibler J, Cereghini S, Heeren J, Stoffel M, Brüning JC
  
• (2013) The actin cross-linker Filamin/Cheerio mediates tumor malignancy downstream of JNK signaling. J Cell Sci 126: 927-38
  Kulshammer E, Uhlirova M
  
• (2013) TRIAP1/PRELI complexes prevent apoptosis by mediating intramitochondrial transport of phosphatidic acid. Cell Metab 18: 287-95
  Potting C, Tatsuta T, Konig T, Haag M, Wai T, Aaltonen MJ, Langer T
  
• (2014) CLUH regulates mitochondrial biogenesis by binding mRNAs of nuclear-encoded mitochondrial proteins. J Cell Biol 207: 213-23
  Gao J, Schatton D, Martinelli P, Hansen H, Pla-Martin D, Barth E, Becker C, Altmueller J, Frommolt P, Sardiello M, Rugarli EI
  
• (2014) DAF-16/FOXO and EGL-27/GATA promote developmental growth in response to persistent somatic DNA damage. Nat Cell Biol 16: 1168-1179
  Mueller MM, Castells-Roca L, Babu V, Ermolaeva MA, Müller RU, Frommolt P, Williams AB, Greiss S, Schneider JI, Benzing T, Schermer B, Schumacher B
  
• (2014) Hexosamine pathway metabolites enhance protein quality control and prolong life. Cell 156: 1167-78
  Denzel MS, Storm NJ, Gutschmidt A, Baddi R, Hinze Y, Jarosch E, Sommer T, Hoppe T, Antebi A
  
• (2014) Loss of UCP2 attenuates mitochondrial dysfunction without altering ROS production and uncoupling activity. PloS Genet 10: e1004385
  Kukat A, Dogan SA, Edgar D, Mourier A, Jacoby C, Maiti P, Mauer J, Becker C, Senft K, Wibom R, Kudin AP, Hultenby K, Flogel U, Rosenkranz S, Ricquier D, Kunz WS, Trifunovic A
  
• (2014) Neonatal insulin action impairs hypothalamic neurocircuit formation in response to maternal high-fat feeding. Cell 156: 495-509
  Vogt MC, Paeger L, Hess S, Steculorum SM, Awazawa M, Hampel B, Neupert S, Nicholls HT, Mauer J, Hausen AC, Predel R, Kloppenburg P, Horvath TL, Brüning JC
  
• (2014) RIPK1 maintains epithelial homeostasis by inhibiting apoptosis and necroptosis. Nature 513: 90-4
  Dannappel M, Vlantis K, Kumari S, Polykratis A, Kim C, Wachsmuth L, Eftychi C, Lin J, Corona T, Hermance N, Zelic M, Kirsch P, Basic M, Bleich A, Kelliher M, Pasparakis M
  
• (2014) Signaling by IL-6 promotes alternative activation of macrophages to limit endotoxemia and obesity-associated resistance to insulin. Nat Immunol 15: 423-30
  Mauer J, Chaurasia B, Goldau J, Vogt MC, Ruud J, Nguyen KD, Theurich S, Hausen AC, Schmitz J, Bronneke HS, Estevez E, Allen TL, Mesaros A, Partridge L, Febbraio MA, Chawla A, Wunderlich FT, Brüning JC
  
• (2014) The i-AAA protease YME1L and OMA1 cleave OPA1 to balance mitochondrial fusion and fission. J Cell Biol 204: 919-29
  Anand R, Wai T, Baker MJ, Kladt N, Schauss AC, Rugarli E, Langer T
  
• (2014) Tissue-specific loss of DARS2 activates stress responses independently of respiratory chain deficiency in the heart. Cell Metab 19: 458-69
  Dogan SA, Pujol C, Maiti P, Kukat A, Wang S, Hermans S, Senft K, Wibom R, Rugarli EI, Trifunovic A
  
• (2014) Unexpected role of the steroid-deficiency protein ecdysoneless in pre-mRNA splicing. PloS Genet 10: e1004287
  Claudius AK, Romani P, Lamkemeyer T, Jindra M, Uhlirova M
  
• (2015) A critical period for experience-dependent remodeling of adult-born neuron connectivity. Neuron 85: 710-7
  Bergami M, Masserdotti G, Temprana SG, Motori E, Eriksson TM, Gobel J, Yang SM, Conzelmann KK, Schinder AF, Gotz M, Berninger B
  
• (2015) A synergistic interaction between Chk1- and MK2 inhibitors in KRAS-mutant cancer. Cell Jul 2, 162(1): 146-159
  Dietlein F, Kalb B, Jokic M, Noll EM, Strong A, Tharun A, Ozretić L, Künstlinger H, Kambartel K, Randerath WJ, Jüngst C, Schmitt A, Torgovnick A, Richters A, Rauh D, Siedek F, Persigehl T, Mauch C, Bartkova J, Bradley A, Sprick MR, Trumpp A, Rad R, Saur D, Bartek J, Wolf J, Büttner R, Thomas RK, Reinhardt HC
  
• (2015) Hypothalamic Agrp neurons drive stereotypic behaviors beyond feeding. Cell 160: 1222-32
  Dietrich MO, Zimmer MR, Bober J, Horvath TL
  
• (2015) Hypothalamic POMC neurons promote cannabinoidinduced feeding. Nature 519: 45-50
  Koch M, Varela L, Kim JG, Kim JD, Hernandez-Nuno F, Simonds SE, Castorena CM, Vianna CR, Elmquist JK, Morozov YM, Rakic P, Bechmann I, Cowley MA, Szigeti-Buck K, Dietrich MO, Gao XB, Diano S, Horvath TL
  
• (2015) Hypothalamic UDP Increases in Obesity and Promotes Feeding via P2Y6-Dependent Activation of AgRP Neurons. Cell 162: 1404-17
  Steculorum SM, Paeger L, Bremser S, Evers N, Hinze Y, Idzko M, Kloppenburg P, Brüning JC
  
• (2015) Imbalanced OPA1 processing and mitochondrial fragmentation cause heart failure in mice. Science 350: aad0116
  Wai T, Garcia-Prieto J, Baker MJ, Merkwirth C, Benit P, Rustin P, Ruperez FJ, Barbas C, Ibanez B, Langer T
  
• (2015) Interplay among Drosophila transcription factors Ets21c, Fos and Ftz-F1 drives JNK-mediated tumor malignancy. Dis Model Mech 8: 1279-93
  Kulshammer E, Mundorf J, Kilinc M, Frommolt P, Wagle P, Uhlirova M
  
• (2015) The Ras-Erk-ETS signalling pathway is a drug target for longevity. Cell 162: 72-83
  Slack C, Alic N, Foley A, Cabecinha M, Hoddinott MP, Partridge L
  
• (2016) AgRP Neurons Control Systemic Insulin Sensitivity via Myostatin Expression in Brown Adipose Tissue. Cell 165: 125-138
  Steculorum SM, Ruud J, Karakasilioti I, Backes H, Engstrom Ruud L, Timper K, Hess ME, Tsaousidou E, Mauer J, Vogt MC, Paeger L, Bremser S, Klein AC, Morgan DA, Frommolt P, Brinkkotter PT, Hammerschmidt P, Benzing T, Rahmouni K, Wunderlich FT et al.
  
• (2016) Chromatin-associated degradation is defined by UBXN-3/FAF1 to safeguard DNA replication fork progression. Nat Commun 7: 10612
  Franz A, Pirson PA, Pilger D, Halder S, Achuthankutty D, Kashkar H, Ramadan K, Hoppe T
  
• (2016) CLPP coordinates mitoribosomal assembly through the regulation of ERAL1 levels. EMBO J 35: 2566-2583
  Szczepanowska K, Maiti P, Kukat A, Hofsetz E, Nolte H, Senft K, Becker C, Ruzzenente B, Hornig- Do HT, Wibom R, Wiesner RJ, Krüger M, Trifunovic A
  
• (2016) Dicer1-miR-328-Bace1 signalling controls brown adipose tissue differentiation and function. Nat Cell Biol 18: 328-36
  Oliverio M, Schmidt E, Mauer J, Baitzel C, Hansmeier N, Khani S, Konieczka S, Pradas-Juni M, Brodesser S, Van TM, Bartsch D, Bronneke HS, Heine M, Hilpert H, Tarcitano E, Garinis GA, Frommolt P, Heeren J, Mori MA, Brüning JC et al.
  
• (2016) E4 ligase-specific ubiquitination hubs coordinate DNA double-strand-break repair and apoptosis. Nat Struct Mol Biol 23: 995-1002
  Ackermann L, Schell M, Pokrzywa W, Kevei E, Gartner A, Schumacher B, Hoppe T
  
• (2016) Hypothalamic feedforward inhibition of thalamocortical network controls arousal and consciousness. Nat Neurosci 19: 290-8
  Herrera CG, Cadavieco MC, Jego S, Ponomarenko A, Korotkova T, Adamantidis A
  
• (2016) Importance of rare gene copy number alterations for personalized tumor characterization and survival analysis. Genome Biol 17: 204
  Seifert M, Friedrich B, Beyer A
  
• (2016) Insulin and TOR signal in parallel through FOXO and S6K to promote epithelial wound healing. Nat Commun 7: 12972
  Kakanj P, Moussian B, Gronke S, Bustos V, Eming SA, Partridge L, Leptin M
  
• (2016) Isavuconazole treatment for mucormycosis: a single-arm open-label trial and case-control analysis. Lancet Infect Dis 16: 828-837
  Marty FM, Ostrosky-Zeichner L, Cornely OA, Mullane KM, Perfect JR, Thompson GR, 3rd, Alangaden GJ, Brown JM, Fredricks DN, Heinz WJ, Herbrecht R, Klimko N, Klyasova G, Maertens JA, Melinkeri SR, Oren I, Pappas PG, Racil Z, Rahav G, Santos R et al.
  
• (2016) Mechanical regulation of transcription drives Polycomb mediated gene silence during lineage I. Nat Cell Biol 18: 864-75
  Le HQ, Ghatak S, Yeung CYC, Tellkamp F, Gunschmann C, Dieterich C, Yeroslaviz A, Habermann B, Pombo A, Niessen CM, Wickström SA
  
• (2016) Mondo complexes regulate TFEB via TOR inhibition to promote longevity in response to gonadal signals. Nat Commun 7: 10944
  Nakamura S, Karalay O, Jager PS, Horikawa M, Klein C, Nakamura K, Latza C, Templer SE, Dieterich C, Antebi A
  
• (2016) mTORC1 and mTORC2 regulate skin morphogenesis and epidermal barrier formation. Nat Commun 7: 13226
  Ding X, Bloch W, Iden S, Ruegg MA, Hall MN, Leptin M, Partridge L, Eming SA
  
• (2016) Myeloid-Cell-Derived VEGF Maintains Brain Glucose Uptake and Limits Cognitive Impairment in Obesity. Cell 165: 882-95
  Jais A, Solas M, Backes H, Chaurasia B, Kleinridders A, Theurich S, Mauer J, Steculorum SM, Hampel B, Goldau J, Alber J, Forster CY, Eming SA, Schwaninger M, Ferrara N, Karsenty G, Brüning JC
  
• (2016) On the dependency of cellular protein levels on mRNA abundance. Cell 165: 535-50
  Liu Y, Beyer A, Aebersold R
  
• (2016) Restricted diet delays accelerated ageing and genomic stress in HAT-repair-deficient mice. Nature 537: 427-431
  Vermeij WP, Dolle ME, Reiling E, Jaarsma D, Payan-Gomez C, Bombardieri CR, Wu H, Roks AJ, Botter SM, van der Eerden BC, Youssef SA, Kuiper RV, Nagarajah B, van Oostrom CT, Brandt RM, Barnhoorn S, Imholz S, Pennings JL, de Bruin A, Gyenis A, Pothof J, Vijg J, van Steeg H, Hoeijmakers JHJ
  
• (2016) RIPK1 counteracts ZBP1-mediated necroptosis to inhibit inflammation. Nature 540: 124-128
  Lin J, Kumari S, Kim C, Van TM, Wachsmuth L, Polykratis A, Pasparakis M
  
• (2016) Somatic increase of CCT8 mimics proteostasis of human pluripotent stem cells and extends C. elegans lifespan. Nat Commun 7: 13649
  Noormohammadi A, Khodakarami A, Gutierrez-Garcia R, Lee HJ, Koyuncu S, Konig T, Schindler C, Saez I, Fatima A, Dieterich C, Vilchez D
  
• (2016) The Mitochondrial m-AAA Protease Prevents Demyelination and Hair Greying. PloS Genet 12: e1006463
  Wang S, Jacquemyn J, Murru S, Martinelli P, Barth E, Langer T, Niessen CM, Rugarli EI
  
• (2016) The ubiquitin ligase Ubr4 controls stability of podocin/MEC-2 supercomplexes. Hum Mol Genet 25: 1328-44
  Rinschen MM, Bharill P, Wu X, Kohli P, Reinert MJ, Kretz O, Saez I, Schermer B, Hohne M, Bartram MP, Aravamudhan S, Brooks BR, Vilchez D, Huber TB, Müller RU, Krüger M, Benzing T
  
• (2016). Loss of OMA1 delays neurodegeneration by preventing stress-induced OPA1 processing in mitochondria. J Cell Biol. 212, 157-166
  Korwitz A, Merkwirth C, Richter-Dennerlein R, Tröder SE, Sprenger HG, Quiros PM, López- Otín C, Rugarli EI, Langer T
  
• (2017) A microRNA screen reveals that elevated hepatic ectodysplasin A expression contributes to obesity-induced insulin resistance in skeletal muscle. Nat Med 23: 1466-1473
  Awazawa M, Gabel P, Tsaousidou E, Nolte H, Krüger M, Schmitz J, Ackermann PJ, Brandt C, Altmuller J, Motameny S, Wunderlich FT, Kornfeld JW, Bluher M, Brüning JC
  
• (2017) A post-transcriptional program coordinated by CSDE1 prevents intrinsic neural differentiation of human embryonic stem cells. Nat Commun 8: 1456
  Ju Lee H, Bartsch D, Xiao C, Guerrero S, Ahuja G, Schindler C, Moresco JJ, Yates JR, 3rd, Gebauer F, Bazzi H, Dieterich C, Kurian L, Vilchez D
  
• (2017) DARS2 protects against neuroinflammation and apoptotic neuronal loss, but is dispensable for myelin producing cells. Hum Mol Genet 26: 4181-4189
  Aradjanski M, Dogan SA, Lotter S, Wang S, Hermans S, Wibom R, Rugarli E, Trifunovic A
  
• (2017) Dynamic changes in the mouse skeletal muscle proteome during denervation-induced atrophy. Dis Model Mech 10: 881-896
  Lang F, Aravamudhan S, Nolte H, Turk C, Holper S, Muller S, Gunther S, Blaauw B, Braun T, Krüger M
  
• (2017) E-cadherin integrates mechanotransduction and EGFR signaling to control junctional tissue polarization and tight junction positioning. Nat Commun 8: 1250
  Rübsam M, Mertz AF, Kubo A, Marg S, Jungst C, Goranci-Buzhala G, Schauss AC, Horsley V, Dufresne ER, Moser M, Ziegler W, Amagai M, Wickström SA, Niessen CM
  
• (2017) Energy imbalance alters Ca2+ handling and excitability of POMC neurons. Elife 6
  Paeger L, Pippow A, Hess S, Paehler M, Klein AC, Husch A, Pouzat C, Brüning JC, Kloppenburg P
  
• (2017) Gamma oscillations organize top-down signalling to hypothalamus and enable food seeking. Nature 542: 232-236
  Carus-Cadavieco M, Gorbati M, Ye L, Bender F, van der Veldt S, Kosse C, Borgers C, Lee SY, Ramakrishnan C, Hu Y, Denisova N, Ramm F, Volitaki E, Burdakov D, Deisseroth K, Ponomarenko A, Korotkova T
  
• (2017) IL-6/Stat3-Dependent Induction of a Distinct, Obesity-Associated NK Cell Subpopulation Deteriorates Energy and Glucose Homeostasis. Cell Metab 26: 171-184
  Theurich S, Tsaousidou E, Hanssen R, Lempradl AM, Mauer J, Timper K, Schilbach K, Folz- Donahue K, Heilinger C, Sexl V, Pospisilik JA, Wunderlich FT, Brüning JC
  
• (2017) Inflammation and metabolism in tissue repair and regeneration. Science 356: 1026-1030
  Eming SA, Wynn TA, Martin P
  
• (2017) Multilayered Reprogramming in Response to Persistent HAT Damage in C. elegans. Cell Rep 20: 2026-2043
  Edifizi D, Nolte H, Babu V, Castells-Roca L, Mueller MM, Brodesser S, Krüger M, Schumacher B
  
• (2017) Retrograde transport of TrkB-containing autophagosomes via the adaptor AP-2 mediates neuronal complexity and prevents neurodegeneration. Nat Commun 8: 14819
  Kononenko NL, Classen GA, Kuijpers M, Puchkov D, Maritzen T, Tempes A, Malik AR, Skalecka A, Bera S, Jaworski J, Haucke V
  
• (2017) Small nucleoli are a cellular hallmark of longevity. Nat Commun 8: 16083
  Tiku V, Jain C, Raz Y, Nakamura S, Heestand B, Liu W, Spath M, Suchiman HED, Müller RU, Slagboom PE, Partridge L, Antebi A
  
• (2017) The epidermal polarity protein Par3 is a non-cell autonomous suppressor of malignant melanoma. J Exp Med 214: 339-358
  Mescher M, Jeong P, Knapp SK, Rubsam M, Saynisch M, Kranen M, Landsberg J, Schlaak M, Mauch C, Tuting T, Niessen CM, Iden S
  
• (2017) The ubiquitin ligase CHIP integrates proteostasis and aging by regulation of insulin receptor turnover. Cell 169: 470-82
  Tawo R, Pokrzywa W, Kevei E, Akyuz ME, Balaji V, Arian S, Höhfeld J, Hoppe T
  
• (2017) YAP-mediated mechanotransduction determines the podocyte’s response to damage. Sci Signal 10
  Rinschen MM, Grahammer F, Hoppe AK, Kohli P, Hagmann H, Kretz O, Bertsch S, Hohne M, Gobel H, Bartram MP, Gandhirajan RK, Krüger M, Brinkkoetter PT, Huber TB, Kann M, Wickström SA, Benzing T, Schermer B
  
• (2017). IL-6 Improves Energy and Glucose Homeostasis in Obesity via Enhanced Central IL-6 trans-Signaling. Cell Rep. 2017 Apr 11;19(2):267-280
  Timper K, Denson JL, Steculorum SM, Heilinger C, Engström-Ruud L, Wunderlich CM, Rose- John S, Wunderlich FT, Brüning JC
  
• (2017). The Sense of Smell Impacts Metabolic Health and Obesity. Cell Metab. 2017 Jul 5;26(1):198- 211.e5
  Riera CE, Tsaousidou E, Halloran J, Follett P, Hahn O, Pereira MMA, Ruud LE, Alber J, Tharp K, Anderson CM, Brönneke H, Hampel B, Filho CDM, Stahl A, Brüning JC, Dillin A
  
• 2017). Serine ADP-Ribosylation depends on HPF1. Mol Cell Mar 2;65(5):932- 940.e6
  Bonfiglio JJ, Fontana P, Zhang Q, Colby T, Gibbs-Seymour I, Atanassov I, Bartlett E, Zaja R, Ahel I, Matic I
  
• (2018) Adhesion forces and cortical tension couple cell proliferation and differentiation to drive epidermal stratification. Nat Cell Biol 20: 69-80
  Miroshnikova YA, Le HQ, Schneider D, Thalheim T, Rubsam M, Bremicker N, Polleux J, Kamprad N, Tarantola M, Wang I, Balland M, Niessen CM, Galle J, Wickstöm SA
  
• (2018) Diet-Induced Growth Is Regulated via Acquired Leptin Resistance and Engages a Pomc-Somatostatin-Growth Hormone Circuit. Cell Rep. May 8; 23(6): 1728–1741
  Löhr H, Hess S, Pereira MMA, Reinoß P, Leibold S, Schenkel C, Wunderlich CM, Kloppenburg P, Brüning JC, Hammerschmidt M
  
• (2018) Food Perception Primes Hepatic ER Homeostasis viaMelanocortin-Dependent Control of mTOR Acti-vation. Cell 175, 1321–1335
  Brandt C, Nolte H, Henschke S, Engstrom Ruud L, Awazawa M, Morgan DA, Gabel P, Sprenger H-G, Hess ME, Günther S, Langer T, Rahmouni K, Fenselau F, Krüger M, Brüning JC
  
• (2018). AATF suppresses apoptosis, promotes proliferation and is critical for Krasdriven lung cancer. Oncogene 2018 Mar;37(11):1503-1518
  Welcker D, Jain M, Khurshid S, Jokić M, Höhne M, Schmitt A; Frommolt P, Niessen CM, Spiro J, Persigehl T, Witterheim M, Büttner R, Fanciulli M, Schermer B, Reinhardt HC, Benzing T, Höpker K
  
• (2018). Atf3 links loss of epithelial polarity to defects in cell differentiation and cytoarchitecture. PloS Genet 14: e1007241–32
  Donohoe CD, Csordás G, Correia A, Jindra M, Klein C, Habermann B, Uhlirova M
  
• (2018). CLPP deficiency protects against metabolic syndrome but hinders adaptive thermogenesis. EMBO Rep. 2018 Mar 27. Pii: e45126
  Becker C, Kukat A, Szczepanowska K, Hermans S, Senft K, Brandscheid CP, Maiti P, Trifunovic A
  
• (2018). Loss of the mitochondrial i-AAA protease YME1L leads to ocular dysfunction and spinal axonopathy. EMBO Mol Med. 2018 Nov 2. Pii: e9288
  Sprenger HG, Wani G, Hesseling A, König T, Patron M, MacVicar T, Ahola S, Wai T, Barth E, Rugarli EI, Bergami M, Langer T
  
• (2018). The Cdkn1aSUPER Mouse as a Tool to Study p53-Mediated Tumor Suppression. Cell Rep. 2018 Oct 23;25(4):1027-1039.e6
  Torgovnick A, Heger JM, Liaki V, Isensee J, Schmitt A, Knittel G, Riabinska A, Beleggia F, Laurien L, Leeser U, Jüngst C, Siedek F, Vogel W, Klümper N, Nolte H, Wittersheim M, Tharun L, Castiglione R, Krüger M, Schauss A, Perner S, Pasparakis M, Büttner R, Persigehl T, Hucho T, Herter-Sprie GS, Schumacher B, Reinhardt HC
  
• L (2017) A proteomic atlas of insulin signaling reveals tissue-specific mechanisms of longevity assurance. Mol Syst Biol 13: 939
  Tain LS, Sehlke R, Jain C, Chokkalingam M, Nagaraj N, Essers P, Rassner M, Gronke S, Froelich J, Dieterich C, Mann M, Alic N, Beyer A, Partridge L