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24 results on '"Carell, T."'

1. Depletion of pyruvate kinase (PK) activity causes glycolytic intermediate imbalances and reveals a PK-TXNIP regulatory axis

Author

Enginyeria Electrònica, Elèctrica i Automàtica, Universitat Rovira i Virgili, Nieborak A; Lukauskas S; Capellades J; Heyn P; Santos GS; Motzler K; Zeigerer A; Bester R; Protzer U; Schelter F; Wagner M; Carell T; Hruscha A; Schmid B; Yanes O; Schneider R, Enginyeria Electrònica, Elèctrica i Automàtica, Universitat Rovira i Virgili, and Nieborak A; Lukauskas S; Capellades J; Heyn P; Santos GS; Motzler K; Zeigerer A; Bester R; Protzer U; Schelter F; Wagner M; Carell T; Hruscha A; Schmid B; Yanes O; Schneider R

Abstract

Cancer cells convert more glucose into lactate than healthy cells, what results in their growth advantage. Pyruvate kinase (PK) is a key rate limiting enzyme in this process, what makes it a promising potential therapeutic target. However, currently it is still unclear what consequences the inhibition of PK has on cellular processes. Here, we systematically investigate the consequences of PK depletion for gene expression, histone modifications and metabolism.Epigenetic, transcriptional and metabolic targets were analysed in different cellular and animal models with stable knockdown or knockout of PK.Depleting PK activity reduces the glycolytic flux and causes accumulation of glucose-6-phosphate (G6P). Such metabolic perturbation results in stimulation of the activity of a heterodimeric pair of transcription factors MondoA and MLX but not in a major reprogramming of the global H3K9ac and H3K4me3 histone modification landscape. The MondoA:MLX heterodimer upregulates expression of thioredoxin-interacting protein (TXNIP) - a tumour suppressor with multifaceted anticancer activity. This effect of TXNIP upregulation extends beyond immortalised cancer cell lines and is applicable to multiple cellular and animal models.Our work shows that actions of often pro-tumorigenic PK and anti-tumorigenic TXNIP are tightly linked via a glycolytic intermediate. We suggest that PK depletion stimulates the activity of MondoA:MLX transcription factor heterodimers and subsequently, increases cellular TXNIP levels. TXNIP-mediated inhibition of thioredoxin (TXN) can reduce the ability of cells to scavenge reactive oxygen species (ROS) leading to the oxidative damage of cellular structures including DNA. These findings highlight an important regulatory axis affecting tumour suppression mechanisms

Published
2023

2. N6-methyladenosine (m6A) recruits and repels proteins to regulate mRNA homeostasis

Author

Edupuganti, V.S.R.R., Geiger, S., Lindeboom, R.G.H., Shi, H., Hsu, P.J., Lu, Z., Wang, S., Baltissen, M.P.A., Jansen, P. W., Rossa, M., Muller, M, Stunnenberg, H., He, C., Carell, T., Vermeulen, M., Edupuganti, V.S.R.R., Geiger, S., Lindeboom, R.G.H., Shi, H., Hsu, P.J., Lu, Z., Wang, S., Baltissen, M.P.A., Jansen, P. W., Rossa, M., Muller, M, Stunnenberg, H., He, C., Carell, T., and Vermeulen, M.

Abstract

Contains fulltext : 177835.pdf (publisher's version ) (Closed access)

Published
2017

3. N6-methyladenosine (m6A) recruits and repels proteins to regulate mRNA homeostasis

Author

Edupuganti, V.S.R.R., Geiger, S., Lindeboom, R.G.H., Shi, H., Hsu, P.J., Lu, Z., Wang, S., Baltissen, M.P.A., Jansen, P. W., Rossa, M., Muller, M, Stunnenberg, H., He, C., Carell, T., Vermeulen, M., Edupuganti, V.S.R.R., Geiger, S., Lindeboom, R.G.H., Shi, H., Hsu, P.J., Lu, Z., Wang, S., Baltissen, M.P.A., Jansen, P. W., Rossa, M., Muller, M, Stunnenberg, H., He, C., Carell, T., and Vermeulen, M.

Abstract

Contains fulltext : 177835.pdf (publisher's version ) (Closed access)

Published
2017

4. Active DNA demethylation at enhancers during the vertebrate phylotypic period

Author

Bogdanovic, O., Smits, A.H., de la Calle Mustienes, E., Tena, J.J., Ford, E., Williams, R., Senanayake, U., Schultz, M.D., Hontelez, S., Kruijsbergen, I. van, Rayon, T., Gnerlich, F., Carell, T., Veenstra, G.J.C., Manzanares, M., Sauka-Spengler, T., Ecker, J.R., Vermeulen, M., Gomez-Skarmeta, J.L., Lister, R., Bogdanovic, O., Smits, A.H., de la Calle Mustienes, E., Tena, J.J., Ford, E., Williams, R., Senanayake, U., Schultz, M.D., Hontelez, S., Kruijsbergen, I. van, Rayon, T., Gnerlich, F., Carell, T., Veenstra, G.J.C., Manzanares, M., Sauka-Spengler, T., Ecker, J.R., Vermeulen, M., Gomez-Skarmeta, J.L., and Lister, R.

Abstract

Contains fulltext : 157230.pdf (publisher's version ) (Closed access)

Published
2016

5. M. Vrabel and T. Carell for Cycloadditions in Bioorthogonal Chemistry

Author

Carell, T., Vrabel, M., Yang, M., Yang, Y., Chen, P.R., Dommerholt, J., Rutjes, F.P.J.T., Delft, F.L. van, Herner, A., Lin, Q., Wu, H., Devaraj, N.K., Kath-Schorr, S., Carell, T., Vrabel, M., Yang, M., Yang, Y., Chen, P.R., Dommerholt, J., Rutjes, F.P.J.T., Delft, F.L. van, Herner, A., Lin, Q., Wu, H., Devaraj, N.K., and Kath-Schorr, S.

Abstract

Item does not contain fulltext

Published
2016

6. Active DNA demethylation at enhancers during the vertebrate phylotypic period

Author

Bogdanovic, O., Smits, A.H., de la Calle Mustienes, E., Tena, J.J., Ford, E., Williams, R., Senanayake, U., Schultz, M.D., Hontelez, S., Kruijsbergen, I. van, Rayon, T., Gnerlich, F., Carell, T., Veenstra, G.J.C., Manzanares, M., Sauka-Spengler, T., Ecker, J.R., Vermeulen, M., Gomez-Skarmeta, J.L., Lister, R., Bogdanovic, O., Smits, A.H., de la Calle Mustienes, E., Tena, J.J., Ford, E., Williams, R., Senanayake, U., Schultz, M.D., Hontelez, S., Kruijsbergen, I. van, Rayon, T., Gnerlich, F., Carell, T., Veenstra, G.J.C., Manzanares, M., Sauka-Spengler, T., Ecker, J.R., Vermeulen, M., Gomez-Skarmeta, J.L., and Lister, R.

Abstract

Contains fulltext : 157230.pdf (publisher's version ) (Closed access)

Published
2016

7. M. Vrabel and T. Carell for Cycloadditions in Bioorthogonal Chemistry

Author

Carell, T., Vrabel, M., Yang, M., Yang, Y., Chen, P.R., Dommerholt, J., Rutjes, F.P.J.T., Delft, F.L. van, Herner, A., Lin, Q., Wu, H., Devaraj, N.K., Kath-Schorr, S., Carell, T., Vrabel, M., Yang, M., Yang, Y., Chen, P.R., Dommerholt, J., Rutjes, F.P.J.T., Delft, F.L. van, Herner, A., Lin, Q., Wu, H., Devaraj, N.K., and Kath-Schorr, S.

Abstract

Contains fulltext : 166241.pdf (Publisher’s version ) (Open Access)

Published
2016

8. Active DNA demethylation at enhancers during the vertebrate phylotypic period

Author

Bogdanovic, O., Smits, A.H., de la Calle Mustienes, E., Tena, J.J., Ford, E., Williams, R., Senanayake, U., Schultz, M.D., Hontelez, S., Kruijsbergen, I. van, Rayon, T., Gnerlich, F., Carell, T., Veenstra, G.J.C., Manzanares, M., Sauka-Spengler, T., Ecker, J.R., Vermeulen, M., Gomez-Skarmeta, J.L., Lister, R., Bogdanovic, O., Smits, A.H., de la Calle Mustienes, E., Tena, J.J., Ford, E., Williams, R., Senanayake, U., Schultz, M.D., Hontelez, S., Kruijsbergen, I. van, Rayon, T., Gnerlich, F., Carell, T., Veenstra, G.J.C., Manzanares, M., Sauka-Spengler, T., Ecker, J.R., Vermeulen, M., Gomez-Skarmeta, J.L., and Lister, R.

Abstract

Contains fulltext : 157230.pdf (publisher's version ) (Closed access)

Published
2016

9. M. Vrabel and T. Carell for Cycloadditions in Bioorthogonal Chemistry

Author

Carell, T., Vrabel, M., Yang, M., Yang, Y., Chen, P.R., Dommerholt, J., Rutjes, F.P.J.T., Delft, F.L. van, Herner, A., Lin, Q., Wu, H., Devaraj, N.K., Kath-Schorr, S., Carell, T., Vrabel, M., Yang, M., Yang, Y., Chen, P.R., Dommerholt, J., Rutjes, F.P.J.T., Delft, F.L. van, Herner, A., Lin, Q., Wu, H., Devaraj, N.K., and Kath-Schorr, S.

Abstract

Contains fulltext : 166241.pdf (Publisher’s version ) (Open Access)

Published
2016

11. Characterization of acute myeloid leukemia based on levels of global hydroxymethylation

Author

Kroeze, L., Aslanyan, M.G., Rooij, A. van, Koorenhof-Scheele, T.N., Massop, M., Carell, T., Boezeman, J.B., Marie, J.P., Halkes, C.J., Witte, T.J.M. de, Huls, G.A., Suciu, S., Wevers, R.A., Reijden, B.A. van der, Jansen, J.H., Kroeze, L., Aslanyan, M.G., Rooij, A. van, Koorenhof-Scheele, T.N., Massop, M., Carell, T., Boezeman, J.B., Marie, J.P., Halkes, C.J., Witte, T.J.M. de, Huls, G.A., Suciu, S., Wevers, R.A., Reijden, B.A. van der, and Jansen, J.H.

Abstract

Contains fulltext : 137617.pdf (publisher's version ) (Closed access), Patients with acute myeloid leukemia (AML) frequently harbor mutations in genes involved in the DNA (hydroxy)methylation pathway (DNMT3A, TET2, IDH1, and IDH2). In this study, we measured 5-hydroxymethylcytosine (5hmC) levels in 206 clinically and molecularly well-characterized younger adult AML patients (

Published
2014

12. Tet oxidizes thymine to 5-hydroxymethyluracil in mouse embryonic stem cell DNA

Author

Pfaffeneder, T., Spada, F., Wagner, M., Brandmayr, C., Laube, S.K., Eisen, D., Truss, M., Steinbacher, J., Hackner, B., Kotljarova, O., Schuermann, D., Michalakis, S., Kosmatchev, O., Schiesser, S., Steigenberger, B., Raddaoui, N., Kashiwazaki, G., Muller, U., Spruijt, C.G., Vermeulen, M., Leonhardt, H., Schar, P., Muller, M., Carell, T., Pfaffeneder, T., Spada, F., Wagner, M., Brandmayr, C., Laube, S.K., Eisen, D., Truss, M., Steinbacher, J., Hackner, B., Kotljarova, O., Schuermann, D., Michalakis, S., Kosmatchev, O., Schiesser, S., Steigenberger, B., Raddaoui, N., Kashiwazaki, G., Muller, U., Spruijt, C.G., Vermeulen, M., Leonhardt, H., Schar, P., Muller, M., and Carell, T.

Abstract

Item does not contain fulltext

Published
2014

13. Characterization of acute myeloid leukemia based on levels of global hydroxymethylation

Author

Kroeze, L., Aslanyan, M.G., Rooij, A. van, Koorenhof-Scheele, T.N., Massop, M., Carell, T., Boezeman, J.B., Marie, J.P., Halkes, C.J., Witte, T.J.M. de, Huls, G.A., Suciu, S., Wevers, R.A., Reijden, B.A. van der, Jansen, J.H., Kroeze, L., Aslanyan, M.G., Rooij, A. van, Koorenhof-Scheele, T.N., Massop, M., Carell, T., Boezeman, J.B., Marie, J.P., Halkes, C.J., Witte, T.J.M. de, Huls, G.A., Suciu, S., Wevers, R.A., Reijden, B.A. van der, and Jansen, J.H.

Abstract

Contains fulltext : 137617.pdf (publisher's version ) (Closed access), Patients with acute myeloid leukemia (AML) frequently harbor mutations in genes involved in the DNA (hydroxy)methylation pathway (DNMT3A, TET2, IDH1, and IDH2). In this study, we measured 5-hydroxymethylcytosine (5hmC) levels in 206 clinically and molecularly well-characterized younger adult AML patients (

Published
2014

14. Tet oxidizes thymine to 5-hydroxymethyluracil in mouse embryonic stem cell DNA

Author

Pfaffeneder, T., Spada, F., Wagner, M., Brandmayr, C., Laube, S.K., Eisen, D., Truss, M., Steinbacher, J., Hackner, B., Kotljarova, O., Schuermann, D., Michalakis, S., Kosmatchev, O., Schiesser, S., Steigenberger, B., Raddaoui, N., Kashiwazaki, G., Muller, U., Spruijt, C.G., Vermeulen, M., Leonhardt, H., Schar, P., Muller, M., Carell, T., Pfaffeneder, T., Spada, F., Wagner, M., Brandmayr, C., Laube, S.K., Eisen, D., Truss, M., Steinbacher, J., Hackner, B., Kotljarova, O., Schuermann, D., Michalakis, S., Kosmatchev, O., Schiesser, S., Steigenberger, B., Raddaoui, N., Kashiwazaki, G., Muller, U., Spruijt, C.G., Vermeulen, M., Leonhardt, H., Schar, P., Muller, M., and Carell, T.

Abstract

Item does not contain fulltext

Published
2014

15. Characterization of acute myeloid leukemia based on levels of global hydroxymethylation

Author

Kroeze, L., Aslanyan, M.G., Rooij, A. van, Koorenhof-Scheele, T.N., Massop, M., Carell, T., Boezeman, J.B., Marie, J.P., Halkes, C.J., Witte, T.J.M. de, Huls, G.A., Suciu, S., Wevers, R.A., Reijden, B.A. van der, Jansen, J.H., Kroeze, L., Aslanyan, M.G., Rooij, A. van, Koorenhof-Scheele, T.N., Massop, M., Carell, T., Boezeman, J.B., Marie, J.P., Halkes, C.J., Witte, T.J.M. de, Huls, G.A., Suciu, S., Wevers, R.A., Reijden, B.A. van der, and Jansen, J.H.

Abstract

Contains fulltext : 137617.pdf (publisher's version ) (Closed access), Patients with acute myeloid leukemia (AML) frequently harbor mutations in genes involved in the DNA (hydroxy)methylation pathway (DNMT3A, TET2, IDH1, and IDH2). In this study, we measured 5-hydroxymethylcytosine (5hmC) levels in 206 clinically and molecularly well-characterized younger adult AML patients (

Published
2014

16. DNA methylation and differential gene regulation in photoreceptor cell death.

Author

Farinelli, Pietro, Perera, A, Arango-Gonzalez, B, Trifunovic, D, Wagner, M, Carell, T, Biel, M, Zrenner, E, Michalakis, S, Paquet-Durand, Francois, Ekström, Per, Farinelli, Pietro, Perera, A, Arango-Gonzalez, B, Trifunovic, D, Wagner, M, Carell, T, Biel, M, Zrenner, E, Michalakis, S, Paquet-Durand, Francois, and Ekström, Per

Abstract

Retinitis pigmentosa (RP) defines a group of inherited degenerative retinal diseases causing progressive loss of photoreceptors. To this day, RP is still untreatable and rational treatment development will require a thorough understanding of the underlying cell death mechanisms. Methylation of the DNA base cytosine by DNA methyltransferases (DNMTs) is an important epigenetic factor regulating gene expression, cell differentiation, cell death, and survival. Previous studies suggested an involvement of epigenetic mechanisms in RP, and in this study, increased cytosine methylation was detected in dying photoreceptors in the rd1, rd2, P23H, and S334ter rodent models for RP. Ultrastructural analysis of photoreceptor nuclear morphology in the rd1 mouse model for RP revealed a severely altered chromatin structure during retinal degeneration that coincided with an increased expression of the DNMT isozyme DNMT3a. To identify disease-specific differentially methylated DNA regions (DMRs) on a genomic level, we immunoprecipitated methylated DNA fragments and subsequently analyzed them with a targeted microarray. Genome-wide comparison of DMRs between rd1 and wild-type retina revealed hypermethylation of genes involved in cell death and survival as well as cell morphology and nervous system development. When correlating DMRs with gene expression data, we found that hypermethylation occurred alongside transcriptional repression. Consistently, motif analysis showed that binding sites of several important transcription factors for retinal physiology were hypermethylated in the mutant model, which also correlated with transcriptional silencing of their respective target genes. Finally, inhibition of DNMTs in rd1 organotypic retinal explants using decitabine resulted in a substantial reduction of photoreceptor cell death, suggesting inhibition of DNA methylation as a potential novel treatment in RP.

Published
2014

17. Dynamic Readers for 5-(Hydroxy)Methylcytosine and Its Oxidized Derivatives

Author

Spruijt, C.G., Gnerlich, F., Smits, A.H., Pfaffeneder, T., Jansen, P.W.T.C., Bauer, C., Münzel, M., Wagner, M., Müller, M., Khan, F., Eberl, H.C., Mensinga, A., Brinkman, A.B., Lephikov, K., Müller, U., Walter, J., Boelens, R., van Ingen, H., Leonhardt, H., Carell, T., Vermeulen, M., Spruijt, C.G., Gnerlich, F., Smits, A.H., Pfaffeneder, T., Jansen, P.W.T.C., Bauer, C., Münzel, M., Wagner, M., Müller, M., Khan, F., Eberl, H.C., Mensinga, A., Brinkman, A.B., Lephikov, K., Müller, U., Walter, J., Boelens, R., van Ingen, H., Leonhardt, H., Carell, T., and Vermeulen, M.

Abstract

Item does not contain fulltext

Published
2013

18. Dynamic readers for 5-(hydroxy)methylcytosine and its oxidized derivatives

Author

Biomolecular Mass Spectrometry and Proteomics, Sub Biomol.Mass Spectrometry & Proteom., Sub NMR Spectroscopy, Spruijt, C.G., Gnerlich, F., Smits, A.H., Pfaffeneder, T., Jansen, P.W.T.C., Bauer, C., Munzel, M., Wagner, M., Müller, M., Khan, F., Eberl, H.C., Mensinga, A., Brinkman, A.B., Lephikov, K., Muller, U., Walter, J., Boelens, R., van Ingen, H., Leonhardt, H., Carell, T., Biomolecular Mass Spectrometry and Proteomics, Sub Biomol.Mass Spectrometry & Proteom., Sub NMR Spectroscopy, Spruijt, C.G., Gnerlich, F., Smits, A.H., Pfaffeneder, T., Jansen, P.W.T.C., Bauer, C., Munzel, M., Wagner, M., Müller, M., Khan, F., Eberl, H.C., Mensinga, A., Brinkman, A.B., Lephikov, K., Muller, U., Walter, J., Boelens, R., van Ingen, H., Leonhardt, H., and Carell, T.

Published
2013

19. Dynamic Readers for 5-(Hydroxy)Methylcytosine and Its Oxidized Derivatives

Author

Spruijt, C.G., Gnerlich, F., Smits, A.H., Pfaffeneder, T., Jansen, P.W.T.C., Bauer, C., Münzel, M., Wagner, M., Müller, M., Khan, F., Eberl, H.C., Mensinga, A., Brinkman, A.B., Lephikov, K., Müller, U., Walter, J., Boelens, R., van Ingen, H., Leonhardt, H., Carell, T., Vermeulen, M., Spruijt, C.G., Gnerlich, F., Smits, A.H., Pfaffeneder, T., Jansen, P.W.T.C., Bauer, C., Münzel, M., Wagner, M., Müller, M., Khan, F., Eberl, H.C., Mensinga, A., Brinkman, A.B., Lephikov, K., Müller, U., Walter, J., Boelens, R., van Ingen, H., Leonhardt, H., Carell, T., and Vermeulen, M.

Abstract

Item does not contain fulltext

Published
2013

20. Dynamic Readers for 5-(Hydroxy)Methylcytosine and Its Oxidized Derivatives

Author

Spruijt, C.G., Gnerlich, F., Smits, A.H., Pfaffeneder, T., Jansen, P.W.T.C., Bauer, C., Münzel, M., Wagner, M., Müller, M., Khan, F., Eberl, H.C., Mensinga, A., Brinkman, A.B., Lephikov, K., Müller, U., Walter, J., Boelens, R., van Ingen, H., Leonhardt, H., Carell, T., Vermeulen, M., Spruijt, C.G., Gnerlich, F., Smits, A.H., Pfaffeneder, T., Jansen, P.W.T.C., Bauer, C., Münzel, M., Wagner, M., Müller, M., Khan, F., Eberl, H.C., Mensinga, A., Brinkman, A.B., Lephikov, K., Müller, U., Walter, J., Boelens, R., van Ingen, H., Leonhardt, H., Carell, T., and Vermeulen, M.

Abstract

Item does not contain fulltext

Published
2013

21. Dynamic readers for 5-(hydroxy)methylcytosine and its oxidized derivatives

Author

Biomolecular Mass Spectrometry and Proteomics, Sub Biomol.Mass Spectrometry & Proteom., Sub NMR Spectroscopy, Spruijt, C.G., Gnerlich, F., Smits, A.H., Pfaffeneder, T., Jansen, P.W.T.C., Bauer, C., Munzel, M., Wagner, M., Müller, M., Khan, F., Eberl, H.C., Mensinga, A., Brinkman, A.B., Lephikov, K., Muller, U., Walter, J., Boelens, R., van Ingen, H., Leonhardt, H., Carell, T., Biomolecular Mass Spectrometry and Proteomics, Sub Biomol.Mass Spectrometry & Proteom., Sub NMR Spectroscopy, Spruijt, C.G., Gnerlich, F., Smits, A.H., Pfaffeneder, T., Jansen, P.W.T.C., Bauer, C., Munzel, M., Wagner, M., Müller, M., Khan, F., Eberl, H.C., Mensinga, A., Brinkman, A.B., Lephikov, K., Muller, U., Walter, J., Boelens, R., van Ingen, H., Leonhardt, H., and Carell, T.

Published
2013

22. Dynamic readers for 5-(hydroxy)methylcytosine and its oxidized derivatives

Author

Biomolecular Mass Spectrometry and Proteomics, Sub Biomol.Mass Spectrometry & Proteom., Sub NMR Spectroscopy, Spruijt, C.G., Gnerlich, F., Smits, A.H., Pfaffeneder, T., Jansen, P.W.T.C., Bauer, C., Munzel, M., Wagner, M., Müller, M., Khan, F., Eberl, H.C., Mensinga, A., Brinkman, A.B., Lephikov, K., Muller, U., Walter, J., Boelens, R., van Ingen, H., Leonhardt, H., Carell, T., Biomolecular Mass Spectrometry and Proteomics, Sub Biomol.Mass Spectrometry & Proteom., Sub NMR Spectroscopy, Spruijt, C.G., Gnerlich, F., Smits, A.H., Pfaffeneder, T., Jansen, P.W.T.C., Bauer, C., Munzel, M., Wagner, M., Müller, M., Khan, F., Eberl, H.C., Mensinga, A., Brinkman, A.B., Lephikov, K., Muller, U., Walter, J., Boelens, R., van Ingen, H., Leonhardt, H., and Carell, T.

Published
2013

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