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1. mTORC1 regulates cell survival under glucose starvation through 4EBP1/2-mediated translational reprogramming of fatty acid metabolism

Author

Levy, Tal, Voeltzke, Kai, Hruby, Laura, Alasad, Khawla, Bas, Zuelal, Snaebjörnsson, Marteinn, Marciano, Ran, Scharov, Katerina, Planque, Mélanie, Vriens, Kim, Christen, Stefan, Funk, Cornelius M., Hassiepen, Christina, Kahler, Alisa, Heider, Beate, Picard, Daniel, Lim, Jonathan K. M., Stefanski, Anja, Bendrin, Katja, Vargas-Toscano, Andres, Kahlert, Ulf D., Stühler, Kai, Remke, Marc, Elkabets, Moshe, Grünewald, Thomas G. P., Reichert, Andreas S., Fendt, Sarah-Maria, Schulze, Almut, Reifenberger, Guido, Rotblat, Barak, and Leprivier, Gabriel

Published
2024
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2. Trigonelline is an NAD+ precursor that improves muscle function during ageing and is reduced in human sarcopenia

Author

Membrez, Mathieu, Migliavacca, Eugenia, Christen, Stefan, Yaku, Keisuke, Trieu, Jennifer, Lee, Alaina K., Morandini, Francesco, Giner, Maria Pilar, Stiner, Jade, Makarov, Mikhail V., Garratt, Emma S., Vasiloglou, Maria F., Chanvillard, Lucie, Dalbram, Emilie, Ehrlich, Amy M., Sanchez-Garcia, José Luis, Canto, Carles, Karagounis, Leonidas G., Treebak, Jonas T., Migaud, Marie E., Heshmat, Ramin, Razi, Farideh, Karnani, Neerja, Ostovar, Afshin, Farzadfar, Farshad, Tay, Stacey K. H., Sanders, Matthew J., Lillycrop, Karen A., Godfrey, Keith M., Nakagawa, Takashi, Moco, Sofia, Koopman, René, Lynch, Gordon S., Sorrentino, Vincenzo, and Feige, Jerome N.

Published
2024
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3. Herz

Author

Christen, Stefan, Banz, Yara, Vogt, Peter, Karlin, Kirill, Cerny, Thomas, Cerny, Thomas, editor, and Karlin, Kirill, editor

Published
2023
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7. Herz

Author

Christen, Stefan, Vogt, Peter, Cerny, Thomas, editor, and Karlin, Kirill, editor

Published
2019
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8. Aneuploid yeast strains exhibit defects in cell growth and passage through START.

Author

Thorburn, Rebecca R, Gonzalez, Christian, Brar, Gloria A, Christen, Stefan, Carlile, Thomas M, Ingolia, Nicholas T, Sauer, Uwe, Weissman, Jonathan S, and Amon, Angelika

Subjects
Chromosomes, Artificial, Yeast, Humans, Saccharomyces cerevisiae, Aneuploidy, Cyclin-Dependent Kinases, Cyclins, Amino Acids, Intracellular Signaling Peptides and Proteins, Saccharomyces cerevisiae Proteins, Repressor Proteins, Signal Transduction, Protein Biosynthesis, Transcription, Genetic, Gene Expression Regulation, Fungal, Active Transport, Cell Nucleus, Metabolome, G1 Phase Cell Cycle Checkpoints, Chromosomes, Artificial, Yeast, Transcription, Genetic, Gene Expression Regulation, Fungal, Active Transport, Cell Nucleus, Developmental Biology, Biological Sciences, Medical and Health Sciences
Abstract

Aneuploidy, a chromosome content that is not a multiple of the haploid karyotype, is associated with reduced fitness in all organisms analyzed to date. In budding yeast aneuploidy causes cell proliferation defects, with many different aneuploid strains exhibiting a delay in G1, a cell cycle stage governed by extracellular cues, growth rate, and cell cycle events. Here we characterize this G1 delay. We show that 10 of 14 aneuploid yeast strains exhibit a growth defect during G1. Furthermore, 10 of 14 aneuploid strains display a cell cycle entry delay that correlates with the size of the additional chromosome. This cell cycle entry delay is due to a delayed accumulation of G1 cyclins that can be suppressed by supplying cells with high levels of a G1 cyclin. Our results indicate that aneuploidy frequently interferes with the ability of cells to grow and, as with many other cellular stresses, entry into the cell cycle.

Published
2013

10. SUCLA2 mutations cause global protein succinylation contributing to the pathomechanism of a hereditary mitochondrial disease

Author

Gut, Philipp, Matilainen, Sanna, Meyer, Jesse G., Pällijeff, Pieti, Richard, Joy, Carroll, Christopher J., Euro, Liliya, Jackson, Christopher B., Isohanni, Pirjo, Minassian, Berge A., Alkhater, Reem A., Østergaard, Elsebet, Civiletto, Gabriele, Parisi, Alice, Thevenet, Jonathan, Rardin, Matthew J., He, Wenjuan, Nishida, Yuya, Newman, John C., Liu, Xiaojing, Christen, Stefan, Moco, Sofia, Locasale, Jason W., Schilling, Birgit, Suomalainen, Anu, and Verdin, Eric

Published
2020
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11. Evidence for an alternative fatty acid desaturation pathway increasing cancer plasticity

Author

Vriens, Kim, Christen, Stefan, Parik, Sweta, Broekaert, Dorien, Yoshinaga, Kazuaki, Talebi, Ali, and Dehairs, Jonas

Subjects
Physiological aspects, Research, Cancer cells -- Physiological aspects -- Research, Cancer research, Fatty acid metabolism -- Research, Cancer, Fatty acids, Lung cancer, Tumors, Neurophysiology, Liver, Liver cancer
Abstract

Author(s): Kim Vriens [sup.1] [sup.2] , Stefan Christen [sup.1] [sup.2] , Sweta Parik [sup.1] [sup.2] [sup.3] [sup.4] , Dorien Broekaert [sup.1] [sup.2] , Kazuaki Yoshinaga [sup.5] [sup.6] , Ali Talebi [...], Most tumours have an aberrantly activated lipid metabolism.sup.1,2 that enables them to synthesize, elongate and desaturate fatty acids to support proliferation. However, only particular subsets of cancer cells are sensitive to approaches that target fatty acid metabolism and, in particular, fatty acid desaturation.sup.3. This suggests that many cancer cells contain an unexplored plasticity in their fatty acid metabolism. Here we show that some cancer cells can exploit an alternative fatty acid desaturation pathway. We identify various cancer cell lines, mouse hepatocellular carcinomas, and primary human liver and lung carcinomas that desaturate palmitate to the unusual fatty acid sapienate to support membrane biosynthesis during proliferation. Accordingly, we found that sapienate biosynthesis enables cancer cells to bypass the known fatty acid desaturation pathway that is dependent on stearoyl-CoA desaturase. Thus, only by targeting both desaturation pathways is the in vitro and in vivo proliferation of cancer cells that synthesize sapienate impaired. Our discovery explains metabolic plasticity in fatty acid desaturation and constitutes an unexplored metabolic rewiring in cancers. In several human and mouse cancer cell lines and carcinomas, a sapienate biosynthesis pathway underpins metabolic plasticity by allowing these cells to bypass stearoyl-CoA desaturase-dependent fatty acid desaturation.

Published
2019
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12. Organ-Specific Cancer Metabolism and Its Potential for Therapy

Author

Elia, Ilaria, Schmieder, Roberta, Christen, Stefan, Fendt, Sarah-Maria, Rosenthal, Walter, Editor-in-chief, Barrett, James E., Series editor, Flockerzi, Veit, Series editor, Frohman, Michael A., Series editor, Geppetti, Pierangelo, Series editor, Hofmann, Franz B., Series editor, Michel, Martin C., Series editor, Page, Clive P., Series editor, Thorburn, Andrew M., Series editor, Wang, KeWei, Series editor, and Herzig, Stephan, editor

Published
2016
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13. Long-term outcome following successful endoscopic closure of tracheo-oesophageal fistulas with two cardiac amplatzer septal occluders in a patient with oesophageal cancer.

Author

Schreder, Theresa, Borbély, Yves, Christen, Stefan, Wiest, Reiner, Räber, Lorenz, and Günther, Gunar

Subjects
ESOPHAGEAL cancer, CANCER patients, FISTULA, CARDIAC patients, MUCUS
Abstract

Acquired tracheo-oesophageal fistulas (TEFs) are rare and challenging complications in the course of oesophageal cancer. While surgery is the only curative treatment option for TEFs many patients are not eligible for surgery. Endoscopic treatment approaches such as tracheal-and/or oesophageal-stenting are available, but associated with complications like the development of new fistulas and mucus retention. Offlabel- use of cardiac amplatzer occluder devices to close TEFs has been reported in few case-reports with inconsistent short-term outcomes. We report a case of successful closure of two adjacent TEFs with two partially overlapping cardiac amplatzer occluder devices. The insertion of a 12 mm and a 9 mm device was successful and without complications. The patient tolerated the cardiac amplatzer-devices well and could resume oral food uptake after 2 months. Two years after closure, the patient remained free of symptoms suggesting complete sealing of the fistulas. [ABSTRACT FROM AUTHOR]

Published
2024
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15. Pyruvate Kinase Isoform Expression Alters Nucleotide Synthesis to Impact Cell Proliferation

Author

Lunt, Sophia Y., Muralidhar, Vinayak, Hosios, Aaron M., Israelsen, William J., Gui, Dan Y., Newhouse, Lauren, Ogrodzinski, Martin, Hecht, Vivian, Xu, Kali, Acevedo, Paula N. Marín, Hollern, Daniel P., Bellinger, Gary, Dayton, Talya L., Christen, Stefan, Elia, Ilaria, Dinh, Anh T., Stephanopoulos, Gregory, Manalis, Scott R., Yaffe, Michael B., Andrechek, Eran R., Fendt, Sarah-Maria, and Vander Heiden, Matthew G.

Published
2015
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17. 4EBP1/2 support tumorigenicity and cell survival during energetic stress by translationally regulating fatty acid synthesis

Author

Levy, Tal, primary, Voeltzke, Kai, additional, Hauffe, Laura, additional, Alasad, Khawla, additional, Snaebjörnsson, Marteinn, additional, Marciano, Ran, additional, Scharov, Katerina, additional, Planque, Mélanie, additional, Vriens, Kim, additional, Christen, Stefan, additional, Funk, Cornelius M, additional, Hassiepen, Christina, additional, Kahler, Alisa, additional, Heider, Beate, additional, Picard, Daniel, additional, Lim, Jonathan KM, additional, Bas, Zuelal, additional, Bendrin, Katja, additional, Vargas-Toscano, Andres, additional, Kahlert, Ulf, additional, Remke, Marc, additional, Elkabets, Moshe, additional, Grünewald, Thomas GP, additional, Reichert, Andreas S., additional, Fendt, Sarah-Maria, additional, Schulze, Almut, additional, Reifenberger, Guido, additional, Rotblat, Barak, additional, and Leprivier, Gabriel, additional

Published
2022
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20. Fatty acid carbon is essential for dNTP synthesis in endothelial cells

Author

Schoors, Sandra, Bruning, Ulrike, Missiaen, Rindert, Queiroz, Karla C.S., Borgers, Gitte, Elia, Ilaria, Zecchin, Annalisa, Cantelmo, Anna Rita, Christen, Stefan, Goveia, Jermaine, Heggermont, Ward, Godde, Lucica, Vinckier, Stefan, Van Veldhoven, Paul P., Eelen, Guy, Schoonjans, Luc, Gerhardt, Holger, Dewerchin, Mieke, Baes, Myriam, De Bock, Katrien, Ghesquiere, Bart, Lunt, Sophia Y., Fendt, Sarah-Maria, and Carmeliet, Peter

Subjects
Physiological aspects, Fatty acids -- Physiological aspects, Carbon -- Physiological aspects, Endothelium -- Physiological aspects, Deoxynucleotides -- Physiological aspects, Deoxyribonucleotides -- Physiological aspects
Abstract

Angiogenesis relies on the proliferation and migration of endothelial cells (1). The importance of endothelial cell proliferation for expansive growth of the vascular network has long been recognized (2). While [...], The metabolism of endothelial cells during vessel sprouting remains poorly studied. Here we report that endothelial loss of CPT1A, a rate-limiting enzyme of fatty acid oxidation (FAO), causes vascular sprouting defects due to impaired proliferation, not migration, of human and murine endothelial cells. Reduction of FAO in endothelial cells did not cause energy depletion or disturb redox homeostasis, but impaired de novo nucleotide synthesis for DNA replication. Isotope labelling studies in control endothelial cells showed that fatty acid carbons substantially replenished the Krebs cycle, and were incorporated into aspartate (a nucleotide precursor), uridine monophosphate (a precursor of pyrimidine nucleoside triphosphates) and DNA. CPT1A silencing reduced these processes and depleted endothelial cell stores of aspartate and deoxyribonucleoside triphosphates. Acetate (metabolized to acetyl-CoA, thereby substituting for the depleted FAO-derived acetyl-CoA) or a nucleoside mix rescued the phenotype of CPT1A-silenced endothelial cells. Finally, CPT1 blockade inhibited pathological ocular angiogenesis in mice, suggesting a novel strategy for blocking angiogenesis.

Published
2015
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26. Inferring causal metabolic signals that regulate the dynamic TORC1‐dependent transcriptome

Author

Oliveira, Ana Paula, Dimopoulos, Sotiris, Busetto, Alberto Giovanni, Christen, Stefan, Dechant, Reinhard, Falter, Laura, Haghir Chehreghani, Morteza, Jozefczuk, Szymon, Ludwig, Christina, Rudroff, Florian, Schulz, Juliane Caroline, González, Asier, Soulard, Alexandre, Stracka, Daniele, Aebersold, Ruedi, Buhmann, Joachim M, Hall, Michael N, Peter, Matthias, Sauer, Uwe, and Stelling, Jörg

Published
2015
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32. Correction: Corrigendum: Fatty acid carbon is essential for dNTP synthesis in endothelial cells

Author

Schoors, Sandra, Bruning, Ulrike, Missiaen, Rindert, Queiroz, Karla C. S., Borgers, Gitte, Elia, Ilaria, Zecchin, Annalisa, Cantelmo, Anna Rita, Christen, Stefan, Goveia, Jermaine, Heggermont, Ward, Goddë, Lucica, Vinckier, Stefan, Van Veldhoven, Paul P., Eelen, Guy, Schoonjans, Luc, Gerhardt, Holger, Dewerchin, Mieke, Baes, Myriam, De Bock, Katrien, Ghesquière, Bart, Lunt, Sophia Y., Fendt, Sarah-Maria, and Carmeliet, Peter

Published
2015
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35. Evidence for an alternative fatty acid desaturation pathway increasing cancer plasticity

Author

UCL - (SLuc) Service de gastro-entérologie et hépatologie pédiatrique, UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, Vriens, Kim, Christen, Stefan, Parik, Sweta, Broekaert, Dorien, Yoshinaga, Kazuaki, Talebi, Ali, Dehairs, Jonas, Escalona-Noguero, Carmen, Schmieder, Roberta, Cornfield, Thomas, Charlton, Catriona, Romero-Pérez, Laura, Rossi, Matteo, Rinaldi, Gianmarco, Orth, Martin F., Boon, Ruben, Kerstens, Axelle, Kwan, Suet Ying, Faubert, Brandon, Méndez-Lucas, Andrés, Kopitz, Charlotte C., Chen, Ting, Fernandez-Garcia, Juan, Duarte, João A. G., Schmitz, Arndt A., Steigemann, Patrick, Najimi, Mustapha, Hägebarth, Andrea, Van Ginderachter, Jo A., Sokal, Etienne, Gotoh, Naohiro, Wong, Kwok-Kin, Verfaillie, Catherine, Derua, Rita, Munck, Sebastian, Yuneva, Mariia, Beretta, Laura, DeBerardinis, Ralph J., Swinnen, Johannes V., Hodson, Leanne, Cassiman, David, Verslype, Chris, Christian, Sven, Grünewald, Sylvia, Grünewald, Thomas G. P., Fendt, Sarah-Maria, UCL - (SLuc) Service de gastro-entérologie et hépatologie pédiatrique, UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, Vriens, Kim, Christen, Stefan, Parik, Sweta, Broekaert, Dorien, Yoshinaga, Kazuaki, Talebi, Ali, Dehairs, Jonas, Escalona-Noguero, Carmen, Schmieder, Roberta, Cornfield, Thomas, Charlton, Catriona, Romero-Pérez, Laura, Rossi, Matteo, Rinaldi, Gianmarco, Orth, Martin F., Boon, Ruben, Kerstens, Axelle, Kwan, Suet Ying, Faubert, Brandon, Méndez-Lucas, Andrés, Kopitz, Charlotte C., Chen, Ting, Fernandez-Garcia, Juan, Duarte, João A. G., Schmitz, Arndt A., Steigemann, Patrick, Najimi, Mustapha, Hägebarth, Andrea, Van Ginderachter, Jo A., Sokal, Etienne, Gotoh, Naohiro, Wong, Kwok-Kin, Verfaillie, Catherine, Derua, Rita, Munck, Sebastian, Yuneva, Mariia, Beretta, Laura, DeBerardinis, Ralph J., Swinnen, Johannes V., Hodson, Leanne, Cassiman, David, Verslype, Chris, Christian, Sven, Grünewald, Sylvia, Grünewald, Thomas G. P., and Fendt, Sarah-Maria

Abstract

Most tumours have an aberrantly activated lipid metabolism1,2 that enables them to synthesize, elongate and desaturate fatty acids to support proliferation. However, only particular subsets of cancer cells are sensitive to approaches that target fatty acid metabolism and, in particular, fatty acid desaturation3. This suggests that many cancer cells contain an unexplored plasticity in their fatty acid metabolism. Here we show that some cancer cells can exploit an alternative fatty acid desaturation pathway. We identify various cancer cell lines, mouse hepatocellular carcinomas, and primary human liver and lung carcinomas that desaturate palmitate to the unusual fatty acid sapienate to support membrane biosynthesis during proliferation. Accordingly, we found that sapienate biosynthesis enables cancer cells to bypass the known fatty acid desaturation pathway that is dependent on stearoyl-CoA desaturase. Thus, only by targeting both desaturation pathways is the in vitro and in vivo proliferation of cancer cells that synthesize sapienate impaired. Our discovery explains metabolic plasticity in fatty acid desaturation and constitutes an unexplored metabolic rewiring in cancers.

Published
2019

38. Abstract 1906: PFKFB4, much more than just a glycolytic gene

Author

Phillips, Emma L., primary, Bethke, Frederic, additional, Balss, Jörg, additional, Pusch, Stefan, additional, Christen, Stefan, additional, Schnölzer, Martina, additional, Habel, Antje, additional, Capper, David, additional, Deimling, Andreas Von, additional, Fendt, Sarah-Maria, additional, Lichter, Peter, additional, and Goidts, Violaine, additional

Published
2018
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39. Evidence for an association between Tako-Tsubo cardiomyopathy and bronchial asthma: Retrospective analysis in a primary care hospital

Author

Von Blotzheim Leonardo Glutz, Christen Stefan, Wieser Stephan, Ulrich Silvia, and Huber Lars C.

Abstract

© Blotzheim et al. Objective: We investigated the prevalence of bronchial asthma in patients with Tako Tsubo Syndrome (TTS). Design: This retrospective case series study was conducted in a primary care hospital in Zurich Switzerland. Data of all patients with newly diagnosed TTS (2002 2012) were assessed electronically by the use of ICD 10. Asthma prevalence was compared to published epidemiologic data. Setting: Bronchial asthma is characterized by airway inflammation and during attack release of endogenous catecholamines. Sympathomimetic drugs are the mainstay of treatment for asthma patients. Likewise catecholamine mediated diffuse microvascular myocardial dysfunction seems to be of critical importance for the development of TTS. Results: 20 cases of TTS were identified. 90 were female showed a median age of 70±13y [25y 90y] an apical and/or midventricular ballooning pattern with preserved basal function and a median initial LVEF of 34±9 [25 55]. 65 of patients underwent coronary angiography to rule out significant coronary artery disease. Hypertension was present in 45 of patients 35 were smokers none was suffering from diabetes. Prevalence of asthma in patients with TTS was significantly higher compared to the normal population (25 vs. 7 p=0.012). In 30 of the TTS patients an iatrogenic cause for development of TTS was identified. Conclusion: Prevalence of asthma was significantly higher in patients with TTS compared to epidemiologic data from an age matched population. Phenotypes of patients developing obstructive ventilatory disease and TTS might share common pathogenic mechanisms beyond the use of bronchodilatators. In addition we identified other iatrogenic etiologies in patients with TTS.

Published
2014

40. α-ketoglutarate orchestrates macrophage activation through metabolic and epigenetic reprogramming

Author

Liu, Pu-Ste, primary, Wang, Haiping, additional, Li, Xiaoyun, additional, Chao, Tung, additional, Teav, Tony, additional, Christen, Stefan, additional, Di Conza, Giusy, additional, Cheng, Wan-Chen, additional, Chou, Chih-Hung, additional, Vavakova, Magdalena, additional, Muret, Charlotte, additional, Debackere, Koen, additional, Mazzone, Massimiliano, additional, Huang, Hsien-Da, additional, Fendt, Sarah-Maria, additional, Ivanisevic, Julijana, additional, and Ho, Ping-Chih, additional

Published
2017
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44. Dual loss of succinate dehydrogenase (SDH) and complex I activity is necessary to recapitulate the metabolic phenotype of SDH mutant tumors

Author

Lorendeau, Doriane, Rinaldi, Gianmarco, Boon, Ruben, Spincemaille, Pieter, Metzger, Kristine, Jäger, Christian, Christen, Stefan, Dong, Xiangyi, Kuenen, Sabine, Voordeckers, Karin, Verstreken, Patrik, Cassiman, David, Vermeersch, Pieter, Verfaillie, Catherine, Hiller, Karsten, Fendt, Sarah-Maria, Lorendeau, Doriane, Rinaldi, Gianmarco, Boon, Ruben, Spincemaille, Pieter, Metzger, Kristine, Jäger, Christian, Christen, Stefan, Dong, Xiangyi, Kuenen, Sabine, Voordeckers, Karin, Verstreken, Patrik, Cassiman, David, Vermeersch, Pieter, Verfaillie, Catherine, Hiller, Karsten, and Fendt, Sarah-Maria

Published
2016

45. Pyruvate Kinase Isoform Expression Alters Nucleotide Synthesis to Impact Cell Proliferation

Author

Harvard University--MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Department of Biology, Massachusetts Institute of Technology. Department of Chemical Engineering, Koch Institute for Integrative Cancer Research at MIT, Lunt, Sophia Y., Muralidhar, Vinayak, Hosios, Aaron Marc, Gui, Dan Yi, Hecht, Vivian, Xu, Kali, Acevedo, Paula N. Marin, Bellinger, Gary, Dayton, Talya Lucia, Dinh, Anh T., Stephanopoulos, Gregory, Manalis, Scott R., Yaffe, Michael B., Vander Heiden, Matthew G., Israelsen, William J., Newhouse, Lauren, Ogrodzinski, Martin, Hollern, Daniel P., Christen, Stefan, Elia, Ilaria, Andrechek, Eran R., Fendt, Sarah-Maria, Manalis, Scott R, Yaffe, Michael B, Hecht, Vivian Chaya, Harvard University--MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Department of Biology, Massachusetts Institute of Technology. Department of Chemical Engineering, Koch Institute for Integrative Cancer Research at MIT, Lunt, Sophia Y., Muralidhar, Vinayak, Hosios, Aaron Marc, Gui, Dan Yi, Hecht, Vivian, Xu, Kali, Acevedo, Paula N. Marin, Bellinger, Gary, Dayton, Talya Lucia, Dinh, Anh T., Stephanopoulos, Gregory, Manalis, Scott R., Yaffe, Michael B., Vander Heiden, Matthew G., Israelsen, William J., Newhouse, Lauren, Ogrodzinski, Martin, Hollern, Daniel P., Christen, Stefan, Elia, Ilaria, Andrechek, Eran R., Fendt, Sarah-Maria, Manalis, Scott R, Yaffe, Michael B, and Hecht, Vivian Chaya

Abstract

Metabolic regulation influences cell proliferation. The influence of pyruvate kinase isoforms on tumor cells has been extensively studied, but whether PKM2 is required for normal cell proliferation is unknown. We examine how PKM2 deletion affects proliferation and metabolism in nontransformed, nonimmortalized PKM2-expressing primary cells. We find that deletion of PKM2 in primary cells results in PKM1 expression and proliferation arrest. PKM1 expression, rather than PKM2 loss, is responsible for this effect, and proliferation arrest cannot be explained by cell differentiation, senescence, death, changes in gene expression, or prevention of cell growth. Instead, PKM1 expression impairs nucleotide production and the ability to synthesize DNA and progress through the cell cycle. Nucleotide biosynthesis is limiting, as proliferation arrest is characterized by severe thymidine depletion, and supplying exogenous thymine rescues both nucleotide levels and cell proliferation. Thus, PKM1 expression promotes a metabolic state that is unable to support DNA synthesis., United States. Dept. of Defense. Congressionally Directed Medical Research Programs (Postdoctoral Award W81XWH-12-1-0466), Smith Family Foundation, Burroughs Wellcome Fund, Damon Runyon Cancer Research Foundation, Stern Family, American Association for Cancer Research, National Cancer Institute (U.S.) (NIH 5P30CA1405141), National Cancer Institute (U.S.) (R01CA168653)

Published
2016

46. Legionella native valve endocarditis case report and review of literature

Author

Baumgartner, Verena Anna, Eich, Gerhard, Christen, Stefan, Chmiel, Corinne, Baumgartner, Verena Anna, Eich, Gerhard, Christen, Stefan, and Chmiel, Corinne

Abstract

Background: Legionella native valve endocarditis is exceedingly rare, and to the best of our knowledge, this is the first case complicated by a septic spleen infarction.

Published
2016

47. Reduction of falls and fractures after permanent pacemaker implantation in elderly patients with sinus node dysfunction

Author

Brenner, Roman, primary, Ammann, Peter, additional, Yoon, See-Il, additional, Christen, Stefan, additional, Hellermann, Jens, additional, Girod, Grégoire, additional, Knaus, Urs, additional, Duru, Firat, additional, Krasniqi, Nazmi, additional, Ramsay, David, additional, Sticherling, Christian, additional, Lippuner, Kurt, additional, and Kühne, Michael, additional

Published
2016
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48. Pyruvate kinase isoform expression alters nucleotide synthesis to impact cell proliferation

Author

Lunt, Sophia Y., Muralidhar, Vinayak, Israelsen, William J., Newhouse, Lauren, Ogrodzinski, Martin, Xu, Kali, Hollern, Daniel P., Bellinger, Gary, Christen, Stefan, Elia, Ilaria, Dinh, Anh T., Stephanopoulos, Gregory, Manalis, Scott R., Yaffe, Michael B., Andrechek, Eran R., Fendt, Sarah-Maria, Vander Heiden, Matthew G., Hosios, Aaron Marc, Gui, Dan Yi, Acevedo, Paula N. Marin, Dayton, Talya Lucia, Manalis, Scott R, Yaffe, Michael B, Hecht, Vivian Chaya, Harvard University--MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Department of Biology, Massachusetts Institute of Technology. Department of Chemical Engineering, Koch Institute for Integrative Cancer Research at MIT, Lunt, Sophia Y., Muralidhar, Vinayak, Hosios, Aaron Marc, Gui, Dan Yi, Hecht, Vivian, Xu, Kali, Acevedo, Paula N. Marin, Bellinger, Gary, Dayton, Talya Lucia, Dinh, Anh T., Stephanopoulos, Gregory, Manalis, Scott R., Yaffe, Michael B., and Vander Heiden, Matthew G.

Subjects
Cellular differentiation, Primary Cell Culture, Pyruvate Kinase, Biology, PKM2, Article, Mice, Animals, Molecular Biology, Cell Proliferation, Regulation of gene expression, Mice, Knockout, Cell growth, Nucleotides, Cell Cycle, Cell Biology, DNA, Cell cycle, Fibroblasts, Embryo, Mammalian, Molecular biology, Cell biology, Gene Expression Regulation, Cell culture, Metabolome, Signal transduction, Pyruvate kinase, Metabolic Networks and Pathways, Signal Transduction
Abstract

Metabolic regulation influences cell proliferation. The influence of pyruvate kinase isoforms on tumor cells has been extensively studied, but whether PKM2 is required for normal cell proliferation is unknown. We examine how PKM2 deletion affects proliferation and metabolism in nontransformed, nonimmortalized PKM2-expressing primary cells. We find that deletion of PKM2 in primary cells results in PKM1 expression and proliferation arrest. PKM1 expression, rather than PKM2 loss, is responsible for this effect, and proliferation arrest cannot be explained by cell differentiation, senescence, death, changes in gene expression, or prevention of cell growth. Instead, PKM1 expression impairs nucleotide production and the ability to synthesize DNA and progress through the cell cycle. Nucleotide biosynthesis is limiting, as proliferation arrest is characterized by severe thymidine depletion, and supplying exogenous thymine rescues both nucleotide levels and cell proliferation. Thus, PKM1 expression promotes a metabolic state that is unable to support DNA synthesis., United States. Dept. of Defense. Congressionally Directed Medical Research Programs (Postdoctoral Award W81XWH-12-1-0466), Smith Family Foundation, Burroughs Wellcome Fund, Damon Runyon Cancer Research Foundation, Stern Family, American Association for Cancer Research, National Cancer Institute (U.S.) (NIH 5P30CA1405141), National Cancer Institute (U.S.) (R01CA168653)

Published
2013

49. Characterization of carbon metabolism and glucose repression in yeasts

Author

Christen, Stefan, Sauer, Uwe, and Stelling, Jörg

Subjects
METABOLISCHE REGULATION, REPRESSORS (MOLECULAR GENETICS), METABOLIC REGULATION, CANDIDA (MYKOLOGIE), KOHLENSTOFFMETABOLISMUS (MIKROORGANISMEN), SACCHAROMYCETACEAE (MYKOLOGIE), GLUKOSE (BIOCHEMIE), Life sciences, CARBON METABOLISM (MICROORGANISMS), REGULATION OF SIGNAL TRANSDUCTION (BIOCOMMUNICATION), ddc:570, REPRESSOREN (MOLEKULARE GENETIK), CANDIDA (MYCOLOGY), REGULATION DER SIGNALTRANSDUKTION (BIOKOMMUNIKATION), SACCHAROMYCETACEAE (MYCOLOGY), GLUCOSE (BIOCHEMISTRY)
Published
2013

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