prof. dr. C.F. (Cor) Calkhoven

Cor Calkhoven studied biology and chemistry at the University of Groningen where he also received his PhD. During his PhD-study he discovered a specific gene regulatory mechanism in cancer and metabolism that laid the foundation for his current work. In 1996, Cor moved to the Max Delbrück Center for Molecular Medicine (MDC) in Berlin, with a Marie Curie Postdoctoral fellowship. In 2000, he was rewarded with a Helmholtz fellowship to start his own research group. At the MDC, he identified mRNA-regulatory elements that control translation of key factors in cellular differentiation and cancer. In 2005, Cor moved to the Leibniz Institute for Age Research - Fritz Lipmann Institute (FLI), in Jena, where his lab developed a research interest in the common regulatory mechanisms of ageing, metabolism and cancer. The current focus of his lab is understanding the mechanisms of gene-regulation that are controlled by the nutrient and energy sensitive mTORC1 signaling pathway, and its involvement in health, disease and lifespan determination. In 2013, Cor’s lab joined ERIBA at the UMCG to continue studying the molecular basis of ageing and age-related diseases.

LIST OF PUBLICATIONS

WooKee Min W., Bruhn C., Grigaravicius P., Zhou Z-W., Li F., Krüger A., Siddeek B., Greulich K-O., Popp O., Meisezahl C., Calkhoven C.F, Bürkle A., Xu X. and Wang Z-Q. (2013) Poly(ADP-ribose) binding to Chk1 at stalled replication forks is required for S-phase checkpoint activation. Nat. Commun. 4:2993

Dey S., Savant S., Teske B.F., Hatzoglou M., Calkhoven C.F. and Wek R.C. (2012) Transcriptional repression of ATF4 by C/EBPb differentially regulates the integrated stress response. J. Biol. Chem. 287, 21936-21949.

Mielke N., Schwarzer R., Calkhoven C.F., Kaufman R., Dorken B., Leutz A. and Jundt F. (2011) Eukaryotic initiation factor 2α phosphorylation is required for B cell maturation and function in mice. Haematologica. 96, 1261-1268.

Luther J., Driessler F., Megges M., Hess A., Herbort B., Mandic V., Zaiss M.M., Reichardt A., Zech C., Tuckermann J.P., Calkhoven C.F., Wagner E.F., Schett G. and David J-P. (2011) Elevated Fra-1 expression causes severe Lipodystrophy. Journal of Cell Science. 124, 1465-76.

Müller, C., Bremer, A., Schreiber, S., Eichwald, S. and Calkhoven, C.F. (2010). Nucleolar retention of a translational C/EBPa isoform stimulates rDNA transcription and cell size. EMBO J. 29, 897-909.

Müller, C. and Calkhoven, C.F (2010). C/EBPa enters the nucleolus. Cell Cycle 9, 1229-1230.

Wethmar, K., Bégay, V., Smink, J.J., Zaragoza, K., Wiesenthal, V., Dörken, B., Calkhoven, C.F. and Leutz, A. (2010). C/EBPbDuORF mice – a genetic model for uORF-mediated translational control in mammals. Genes & Dev. 24, 15-20.

Juenemann K., Weisse C., Reichmann D., Kaether C., Calkhoven C.F., and Schilling G. (2010) Modulation of mutant Huntingtin N-terminal cleavage and its effect on aggregation and cell death. Neurotox Res. 20, 120-33.

Van Gorp, A.G.M., van der Vos, K., Brenkman, A.B., Bremer, A., van den Broek, N., Zwartkruis, F., Hershey, J.W., Burgering, B.M.T., Calkhoven, C.F. and Coffer, P.J. (2008) AGC kinases regulate phosphorylation and activation of eukaryotic translation initiation factor 4B. Oncogene 28, 95-106.

Wiesenthal, V., Leutz, A. and Calkhoven, C.F. (2006). Analysis of translation initiation using a Translation Control Reporter System (TCRS). Nature Protocols 1, 1531-1537.

Wiesenthal, V., Leutz, A. and Calkhoven, C.F. (2006). A Translation Control Reporter System (TCRS) for the analysis of translationally controlled processes in the vertebrate cell. Nucleic Acids Res. 34, e23.

Jundt, F., Raetzel, N., Müller, C., Calkhoven C.F., Kley, K., Mathas, S., Lietz, A., Leutz, A. and Dörken, B. (2005). A rapamycin derivative (everolimus) controls proliferation through down-regulation of truncated CCAAT enhancer binding protein b and NF-kB activity in Hodgkin and anaplastic large cell lymphomas. Blood 106, 1801-1807.

Müller, C., Calkhoven, C.F., Sha, X. and Leutz, A. (2004). C/EBPa Requires a SWI/SNF complex for proliferation arrest. J. Biol. Chem. 279, 7353-7358.

Calkhoven, C.F., Müller, C., Martin, R., Krosl, G., Pietsch, H., Hoang, T. and Leutz, A. (2003). Translational control of SCL isoform expression in hematopoietic lineage choice. Genes & Dev. 17, 959-964.

Calkhoven, C.F.*, Müller, C. and Leutz, A. (2002). Translational control of gene expression and disease. Trends in Molecular Medicine. 8, 577-583.

Calkhoven, C.F.*, Müller, C. and Leutz, A. (2000). Translational control of C/EBPa and C/EBPb isoform expression. Genes & Dev. 14, 1920-1932.

Calkhoven, C.F., Snippe, L., and AB, G. (1997). Differential stimulation by CCAAT / enhancer- binding protein a isoforms of the estrogen- activated promoter of the very- low- density apolipoprotein II gene. Eur. J. Biochem. 249, 113-120.

Calkhoven, C.F., Gringhuis, S., and AB, G. (1997). The chicken CCAAT / enhancer-binding protein a gene. Cloning, characterisation and tissue distribution. Gene 196, 219-229.

Calkhoven, C.F., and AB, G. (1996). Multiple steps in the regulation of transcription- factor level and activity. Biochem. J. 317, 329-342.

Calkhoven, C.F., Bouwman, P. R., Snippe, L., and AB, G. (1994). Translation start site multiplicity of the CCAAT/enhancer binding protein a mRNA is dictated by a small 5' open reading frame. Nucleic Acids Res. 22, 5540-5547.

Calkhoven, C.F., AB, G. and Wijnholds, J. (1992). cC/EBP, a chicken transcription factor of the leucine-zipper C/EBP family. Nucleic Acids Res. 20, 4093.

(*) First- and corresponding author

RECENT LECTURES AND ORAL PRESENTATIONS

2014

Zing conference on the Biology of Human Aging, Oropesa, Spain. mTORC1-C/EBPb regulation of healthspan and its translational implications (invited)

CSHL meeting: Molecular Mechanisms of Aging. Cold Spring Harbor, USA. The physiology of uORF regulation.

Cancer Research UK – London Research Institute, London, UK: c-Myc-mTORC1 and mTORC1-C/EBP regulation in cancer (invited).

Erasmus Medical Centre, Rotterdam, the Netherlands. c-Myc-mTORC1 and mTORC1-C/EBP regulation in leukaemia and lymphoma (invited).

CSHL meeting: Translational Control, Cold Spring Harbor, USA. Session Chair: translation regulatory elements. Introductory talk (invited).

2013

EMBO Conference: Protein synthesis and translational control, EMBL, Heidelberg, Germany. mTORC1-regulated translation of the C/EBPb-mRNA determines health- and life-span in mice.

Cellular Aspects of mRNA fate, 12th International meeting, Université Pierre et Marie Curie Paris, France.Regulation of C/EBPb-mRNA translation through mTORC1/4E-BP signalling controls metabolic reprogramming in mice (invited).

2012

CSHL meeting: Molecular Mechanisms of Aging. Cold Spring Harbor, USA. C/EBPb-mRNA translation links mTORC1 signalling to caloric restriction type metabolic reprogramming in mice.

CSHL meeting: Translational Control, Cold Spring Harbor, USA. uORF-controlled C/EBPb-mRNA translation links mTORC1 signaling to caloric restriction type metabolic reprogramming in mice.

Third Annual Mayo Clinic Robert and Arlene Kogod Center on Aging Conference, Mayo Clinic, Rochester MN, USA. C/EBPb-mRNA translation links mTORC1 signalling to caloric restriction type metabolic reprogramming in mice (invited).

Cell Symposium: Angiogenesis, Metabolic Regulation, and Cancer Biology, Leuven, Belgium. c-Myc suppresses mTORC1 to attenuate mitochondrial respiration and ROS production in cancer cells.

The German Association for Aging Research (DGfA) meeting, Frankfurt, Germany. C/EBPb-mRNA translation links mTORC1 signalling to caloric restriction type metabolic reprogramming in mice (invited).

University Tumor Centrum Research Seminar, University Hospital FSU, Jena, Germany. Cancer Cell Metabolism (invited).

Postgraduate Symposium on Cancer Research, Dornburg, Germany. Myc controls mTORC1 signalling to balance metabolism with survival.

2011

Cell Symposia: Metabolism & Aging. Cape Cod, USA. Abrogation of mTOR controlled C/EBPb-LIP translation improves metabolic performance in mice.

Workshop: Genome, Cancer and Ageing, Monaco. Coupling translational control to life span - Abrogation of mTOR controlled C/EBPb-LIP translation improves metabolic performance in mice.

Medizinische Hochschule Hannover, Germany. Control of mRNA-translation and its potential involvement in cancer (invited).

Jena Centre of the Biology of Ageing (JCBA). Post-transcriptional control of gene expression in Ageing.

Postgraduate Symposium on Cancer Research, Dornburg, Germany. Myc controls mTORC1 signaling to balance metabolism with survival. 

2010

CSHL meeting: Molecular Mechanisms of Aging. Cold Spring Harbor, USA. C/EBPb-uORF deficiency mimics caloric restriction induced metabolic reprogramming in mice.

CSHL meeting: Translational Control, Cold Spring Harbor, USA. The oncomir miR-155 stimulates uORF-dependent translation into the proliferation promoting C/EBPb-LIP.

CSHL meeting: Translational Control, Cold Spring Harbor, USA. TRIM37 associates with the C/EBPa-3’UTR to stimulate C/EBPa-p30 translation.

The German Association for Aging Research (DGfA) meeting, Jena, Germany. Abrogation of mTOR controlled C/EBPb-LIP translation mimics the physiology of caloric restriction in mice

FLI retreat, Oberwiesenthal, Germany.Translation of C/EBPa and -b mRNAs - a matter of Life and Death.

Postgraduate Symposium on Cancer Research, Dornburg, Germany. The oncomir miR-155 stimulates uORF-dependent translation into the proliferation promoting C/EBPb-LIP

Institute of Toxicology and Genetics (ITG) – Karlsruhe Institute of Technology (KIT)/KIT, Karlsruhe, Germany. Translational Control of Gene Expression.

Scientific Advisory Board meeting at the FLI. Coupling translational control to life span –
C/EBPb-uORF deficiency mimics caloric restriction induced metabolic reprogramming