Research Groups

Gene Regulation In Ageing and Age-Related Diseases

Ageing, metabolic disorders and cancer share common biological mechanisms. Cellular factors that are involved in sensing nutrient (food) and energy availability are decisively involved in ageing and lifespan determination as well as in the development of age-related diseases like cancer or metabolic diseases. The primary research focus of the Calkhoven lab is determining how metabolic and other growth signals control the expression of specific sets of genes that can alter the organism’s normal function or contribute to disease.

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  • Cor Calkhoven Visit

    Group leader of the Laboratory of Gene regulation in ageing and age-related diseases

    Research fields

    Transcriptional and post-transcriptional gene regulation, cancer, metabolism, ageing, lifespan determination

    Research Associates
    Christine Müller
    PhD Students
    Clément Karch
    Josephine Hartung
    Gertrud Kortman
  • Currently, the Calkhoven lab studies a specific pathway (mTORC1-pathway) that senses if enough nutrients and energy are available to regulate cell growth, through the control of protein synthesis and/or other metabolic processes. The Calkhoven lab are particular interested in the function of mRNA control elements, protein factors and microRNAs that are involved in mTORC1-controlled processes. Using mouse models they examine the function of these elements, and other factors, on organismal health and life span determination. In addition, they study the modification of gene-regulatory proteins by cellular metabolites and how this regulates cell function under different nutrition conditions. With the aim of ‘translating’ the fundamental research into clinical-pharmacological applications, the lab is also involved in developing reporter-systems for potential compound screening strategies.

    • Ackermann T, Zuidhof HR, Müller C, Kortman G, Rutten MGS, Broekhuis MJC, Zaini MA, Hartleben G and Calkhoven CF.(2023) C/EBPβ-LIP mediated activation of the malate-aspartate shuttle sensitizes cells to glycolysis inhibition.Molecular Metabolism  
    • Zuidhof, H.R. and Calkhoven, C.F. (2022) Oncogenic and tumour-suppressive functions of FTO. Cancer Research.  
    • Müller C, Zidek LM, Eichwald S, Kortman G, Koster M and Calkhoven CF. (2022) Enhanced C/EBPβ function promotes hypertrophic versus hyperplastic fat tissue growth and prevents steatosis in response to high-fat diet feeding. eLife.  
    • Sterken BA, Ackermann T, Zuidhof HR, Kortman G, Hernandez-Segura A, Müller C, Broekhuis M, Spierings D, Gurvey V, and Calkhoven CF. (2022) C/EBPβ isoform-specific regulation of migration and invasion in triple-negative breast cancer cells. NPJ Breast Cancer.  
    • de Leeuw, A, Oude Luttikhuis, MAM, Wellen, AC, Müller, C and Calkhoven C.F. (2021) Obesity and its impact on COVID-19. Journal of Molecular Medicine.
    • Ackermann T, Zuidhof HR, Kortman, G, Rutten, MGS, Broekhuis, M, Zaini, MA, Hartleben, G and Calkhoven, CF. (2020) C/EBPβ-LIP induces the malate aspartate shuttle causing reliance on glycolysis for NADH regeneration and cell survival. BioRxiv.
    • Müller, C, Zidek, LM, Eichwald, S and Calkhoven C.F. (2020) C/EBPβ regulates hypertrophic versus hyperplastic fat tissue growth. BioRxiv.
    • Van der Voort PHJ, Moser J, Zandstra DF, Muller Kobold AC, Knoester M, Calkhoven CF, Hamming I and Meurs M. (2020) Leptin levels in SARS-CoV-2 infection related respiratory failure: A cross-sectional study and a phathophysiological framework on the role of fat tissue. Heliyon.  
    • Niehrs C. and Calkhoven CF. (2020) The emerging role of C/EBPβ and epigenetic DNA methylation in ageing. Trends in Genetics.
    • Bakula D, Ablasser A, Aguzzi A, Antebi A, Barzilai N, Bittner M-I, Borch Jensen M, Calkhoven CF, Chen D, de Grey ADNJ, Feige JN, Georgievskaya A, Gladyshev VN, Golato T, Gudkov AV, Hoppe T, Kaeberlein M, Katajisto P, Kennedy BK, Lal U, Martin-Villalba A, Moskalev AA, Ozerov I, Petr MA, Reason, Rubinsztein DC, Tyshkovskiy A, Vanhaelen Q, Zhavoronkov A, Scheibye-Knudsen M. (2019) Latest advances in aging research and drug discovery. Aging.    
    • Ackermann T, Hartleben G, Müller C, Mastrobuoni G, Groth M, Sterken BA, Zaini MA, Youssef SA, Zuidhof HR, Krauss SR, Kortman G, de Haan G, de Bruin A, Wang Z-Q, Platzer M, Kempa S, Calkhoven CF. (2019) C/EBPβ-LIP induces metabolic reprogramming by regulating the let-7/LIN28B circuit. Commun Biol.
    • Hartleben G, Müller C, Krämer A, Schimmel H, Zidek LM, Dornblut C, Winkler R, Eichwald S, Kortman G, Kosan C, Kluiver J, Petersen I, van den Berg A, Wang Z-Q, Calkhoven. CF. (2018) Tuberous sclerosis complex is required for tumor maintenance in MYC-driven Burkitt’s lymphoma. EMBO Journal.
    • Müller C, Zidek LM, Ackermann T, de Jong T, Liu P, Kliche V, Zaini MA, Kortman G, Harkema L, Verbeek DS, Tuckermann JP, von Maltzahn J, de Bruin A, Guryev V, Wang ZQ, Calkhoven CF. (2018) Reduced expression of C/EBPβ-LIP extends health- and lifespan in mice. Elife.
    • Sahm A, Bens M, Szafranski, K, Holtze S, Groth M, Görlach M, Calkhoven CF, Müller C, Schwab M, Kestler HA, Cellerino A, Burda  H, Hildebrandt T, Dammann  P and Platzer M (2018) Long-lived rodents reveal signatures of positive selection in genes associated with lifespan and eusociality. PLoS Genetics.
    • Zaini MA, Müller C, de Jong TV, Ackermann T, Hartleben G, Kortman G, Gührs KH, Fusetti F, Krämer OH, Guryev V and Calkhoven CF (2018) p300 and SIRT1 regulated acetylation switch of C/EBPα controls mitochondrial function. Cell Reports.
    • Zaini MA, Müller C, de Jong TV, Ackermann T, Hartleben G, Kortman G, Gührs KH, Fusetti F, Krämer OH, Guryev V and Calkhoven CF (2018) p300 and SIRT1 regulated acetylation switch of C/EBPα controls mitochondrial function. Cell Reports.  
    • Hu D, Essig K, Guimaraes JC, Alterauge D, Edelmann S, Heiseke A , Floess S, Klein J, Maiser A, Marschall S, Hrabĕ de Angelis M, Leonhardt H, Calkhoven CF, Huehn J, Krug A, Baumjohann D, Zavolan M and Heissmeyer V (2017) Roquin suppresses PI3K-mTOR signaling to control protein biosynthesis, T cell differentiation and Treg effector function. Immunity
    • Sin O, de Jong T, Kudron M , Zaini A , Aprile FA , Seinstra R, Mata-Cabana A, Stroo E, Willinge Prins R, Martineau C, Wang HH, Hogewerf W, Steinhof A, Wanker EE, Vendruscolo M, Calkhoven CF, Reinke V, Guryev V, Nollen EAA. (2017) Identification of an RNA Pol III-associated regulator of small non-coding RNAs that is linked with disease-associated protein agregation. Molecular Cell.
    • Zaini MA, Müller C, Ackermann T, Reinshagen J, Kortman G, Pless O, Calkhoven CF. (2017) A screening strategy for the discovery of drugs that reduce C/EBPβ-LIP translation with potential calorie restriction mimetic properties. Scientific Reports.
    • In K, Zaini MA, Müller C, Warren AJ, von Lindern M, Calkhoven CF. (2016) Shwachman-Bodian Diamond Syndrome (SBDS) Protein deficiency impairs translation re-initiation from C/EBPa and C/EBPb mRNAs. Nucleic Acids Research.
    • Zidek LM, Ackermann T, Hartleben G, Eichwald S, Kortman G, Kiehntopf M, Leutz A, Sonenberg N, Wang Z-Q, von Maltzahn J, Müller C, and Calkhoven CF. (2015) Deficiency in mTORC1-controlled C/EBPβ-mRNA translation improves metabolic health in mice. EMBO Reports.
    • Min W, Bruhn C, Grigaravicius P, Zhou ZW, Li F, Krüger A, Siddeek B, Greulich KO, Popp O, Meisezahl C, Calkhoven CF, Bürkle A, Xu X, Wang ZQ. (2013) Poly(ADP-ribose) binding to Chk1 at stalled replication forks is required for S-phase checkpoint activation. Nature Communications.
    • Dey S, Savant S, Teske BF, Hatzoglou M, Calkhoven CF, Wek RC. (2012) Transcriptional repression of ATF4 gene by CCAAT/enhancer-binding protein β (C/EBPβ) differentially regulates integrated stress response. The journal of biological chemistry.
    • Mielke N, Schwarzer R, Calkhoven CF, Kaufman RJ, Dörken B, Leutz A, Jundt F. (2011) Eukaryotic initiation factor 2alpha phosphorylation is required for B-cell maturation and function in mice. Haematologica.
    • Luther J, Driessler F, Megges M, Hess A, Herbort B, Mandic V, Zaiss MM, Reichardt A, Zech C, Tuckermann JP, Calkhoven CF, Wagner EF, Schett G, David JP. (2011) Elevated Fra-1 expression causes severe lipodystrophy. Journal of cell science.
    • Juenemann K, Weisse C, Reichmann D, Kaether C, Calkhoven CF, Schilling G. (2010) Modulation of mutant huntingtin N-terminal cleavage and its effect on aggregation and cell death. Neurotoxicity research.
    • Müller C, Calkhoven CF. (2010) C/EBPα enters the nucleolus. Cell Cycle.
    • Müller C, Bremer A, Schreiber S, Eichwald S, Calkhoven CF. (2010) Nucleolar retention of a translational C/EBPalpha isoform stimulates rDNA transcription and cell size. The EMBO Journal.
    • Wethmar K, Bégay V, Smink JJ, Zaragoza K, Wiesenthal V, Dörken B, Calkhoven CF, Leutz A. (2010) C/EBPbetaDeltauORF mice--a genetic model for uORF-mediated translational control in mammals. Genes & Development.
    • van Gorp AG, van der Vos KE, Brenkman AB, Bremer A, van den Broek N, Zwartkruis F, Hershey JW, Burgering BM, Calkhoven CF, Coffer PJ. (2008) AGC kinases regulate phosphorylation and activation of eukaryotic translation initiation factor 4B. Oncogene.
    • Wiesenthal V, Leutz A, Calkhoven CF. (2006) Analysis of translation initiation using a translation control reporter system. Nature Protocols.
    • Wiesenthal V, Leutz A, Calkhoven CF. (2006) A translation control reporter system (TCRS) for the analysis of translationally controlled processes in the vertebrate cell. Nucleic Acids Research.
    • Jundt F, Raetzel N, Müller C, Calkhoven CF, Kley K, Mathas S, Lietz A, Leutz A, Dörken B. (2005) A rapamycin derivative (everolimus) controls proliferation through down-regulation of truncated CCAAT enhancer binding protein {beta} and NF-{kappa}B activity in Hodgkin and anaplastic large cell lymphomas. Blood.
    • Müller C, Calkhoven CF, Sha X, Leutz A. (2003) The CCAAT enhancer-binding protein alpha (C/EBPalpha) requires a SWI/SNF complex for proliferation arrest. The journal of biological chemistry.
    • Calkhoven CF, Müller C, Martin R, Krosl G, Pietsch H, Hoang T, Leutz A. (2003) Translational control of SCL-isoform expression in hematopoietic lineage choice. Genes & Development.
    • Calkhoven CF, Müller C, Leutz A. (2002) Translational control of gene expression and disease. Trends in molecular medicine.
    • Calkhoven CF, Müller C, Leutz A. (2000) Translational control of C/EBPalpha and C/EBPbeta isoform expression. Genes & Development.
    • Calkhoven CF, Snippe L, Ab G. (1997) Differential stimulation by CCAAT/enhancer-binding protein alpha isoforms of the estrogen-activated promoter of the very-low-density apolipoprotein II gene. European journal of biochemistry.
    • Calkhoven CF, Gringhuis SI, Ab G. (1999) The chicken CCAAT/enhancer binding protein alpha gene. Cloning, characterisation and tissue distribution. Gene.
    • Calkhoven CF, Ab G. (1996) Multiple steps in the regulation of transcription-factor level and activity. The biochemical journal.
    • Calkhoven CF, Bouwman PR, Snippe L, Ab G. (1994) Translation start site multiplicity of the CCAAT/enhancer binding protein alpha mRNA is dictated by a small 5' open reading frame. Nucleic Acids Research.
    • Calkhoven CF, Ab G, Wijnholds J. (1992) c/CEPB, a chicken transcription factor of the leucine-zipper C/EBP family [corrected].. Nucleic Acids Research.
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