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Metabolism and Cancer


Research lines

  1. Ribosome biogenesis as a target of cancer therapy: study of the role of RPL5/RPL11/5S rRNA p53 Checkpoint in the Development and Treatment of DBA (Diamond Blackfan Anemia) and the role of c-Myc Driven Ribosome Biogenesis in the development of colorectal cancer.
  1. Role of nutrients in diabetes, obesity cancer and aging through mTORC1/S6K1 signaling: study of the role of amino acids and glucose in driving tumorigenesis and insulin resistance through mTORC1/ S6K1 and the molecular components through which biguanides suppress mTORC1 signaling.
  1. Role of mTORC1 signaling pathway in hepatocarcinoma: identification of the downstream effectors of mTORC1 by which the tumorigenesis is mediated and identification of mechanisms of resistance to RAD001/BEZ235.
  1. Study of molecular mechanisms responsible for the role of E2F1 in cancer: identification of the signaling pathway responsible for the activation of mTOR by E2F1 and the role of E2F1 in hepatocarcinoma.

Selected articles 

 

2017

 
Wise-Draper TM, Moorthy G, Salkeni MA, Karim NA, Thomas HE, Mercer CA, Beg MS, O'Gara S, Olowokure O, Fathallah H, Kozma SC, Thomas G, Rixe O, Desai P, Morris JC. (2017) A Phase Ib Study of the Dual PI3K/mTOR Inhibitor Dactolisib (BEZ235) Combined with Everolimus in Patients with Advanced Solid Malignancies Target Oncol. 2017 Jun;12(3):323-332. doi: 10.1007/s11523-017-0482-9. 
 
Arif A, Terenzi F, Potdar AA, Jia J, Sacks J, China A, Halawani D, Vasu K, Li X, Brown JM, Chen J, Kozma SC, Thomas G, Fox PL. (2017) EPRS is a critical mTORC1-S6K1 effector that influences adiposity in mice.Nature. 2017 Feb 16;542(7641):357-361
 
Gentilella, A.*, Morón-Duran, F., Fuentes, P., Zweig-Rocha, G., Riaño-Canalias, F., Pelletier, J., Ruiz, M., Turón, G., Tauler, A., Castaño, J., Bueno, C., Menéndez, P., Kozma, S. C., and Thomas, G.* Autogenous Control Of 5’TOP mRNA Stability By 40S Ribosomes, Mol Cell. 2017 Jul 6;67(1):55-70.e4. doi: 10.1016/j.molcel.2017.06.005. Epub 2017 Jun 29.  (*) corresponding author 
 
Zabala-Letona A., Arruabarrena-Aristorena A., Martín-Martín N., Fernandez-Ruiz S., Sutherland J.D., Clasquin M., Tomas-Cortazar J., Jimenez J., Torres I., Quang P., Ximenez-Embun P., Bago R.,  Ugalde-Olano A., Loizaga-Iriarte A., Lacasa-Viscasillas I.,  Unda M., Torrano V., Cabrera D.,  van Liempd S.M., Cendon Y., Castro E., Murray S., Revandkar A., Alimonti A., Zhang Y., Barnett A., Lein G., Pirman D., R. Cortazar A., Arreal L., Prudkin L., Astobiza I., Valcarcel-Jimenez L., Zuñiga-García P., Fernandez-Dominguez I., Piva M.,  Caro-Maldonado A., Sánchez-Mosquera P., Castillo-Martín M., Serra V., Beraza N., Gentilella A., Thomas G., Azkargorta M., Elortza F., Farràs R., Olmos D., Efeyan A., Anguita J., Muñoz J., Falcón-Pérez J.M., Barrio R. , Macarulla T., Mato J.M., Martinez-Chantar M.L., Cordon-Cardo C., Aransay A.M., Marks K., Baselga J., Tabernero J., Nuciforo P., Manning B.D., Marjon K., Carracedo A. (2017) mTORC1-dependent AMD1 regulation sustains  polyamine metabolism in prostate cancer.  Nature. 2017 Jul 6;547(7661):109-113.

 
2016
 
Cortes CL, Veiga SR, Almacellas E, Hernández-Losa J, Ferreres JC, Kozma SC, Ambrosio S, Thomas G, Tauler A. (2016) Effect of low doses of actinomycin D on neuroblastoma cell lines. Mol Cancer. 2016 Jan 4;15(1):1.            
 
 YiS. A., UmS. H., Lee, J., Yoo J. H., Bang, S. Y., Park E. K., Lee m. G., NamK. H., Jeon Y. J., Park, J. W., Rhie, J. W., Kozma, S. C., Thomas, G(*). and Han J. W.  S6K1 Phosphorylation of H2B Mediates EZH2 Trimethylation of H3: A Determinant of Early Adipogenesis.  Mol Cell. 2016 May 5;62(3):443-52.. Epub 2016 Apr 14.   IF: 14.018  doi: 10.1016/j.molcel.2016.03.011 (*) corresponding author 
 
Wang F., Alain T., Szretter  K. J., Stephenson K.,  Pol  J. G., Atherton M. J., Hoang H., Fonseca B. D., Zakaria C., Chen L., Rangwala Z., Hesch A., Sin Yan Chan E., Tuinman C., Suthar M. S., Jiang Z., Ashkar A. A., Thomas G., Kozma S. C., Gale M. Jr, K. Fitzgerald A., Diamond M. S., Mossman K., Sonenberg N., Wan Y. and Lichty B.D.  S6K-STING interaction regulates cytosolic DNA-mediated activation of the transcription factor IRF3. Nat Immunol. 2016 May;17(5):514-22. doi:10.1038/ni.3433. Epub 2016 Apr 4.  
 
 2015


Fouladi, M., Perentesis, J., Wagner, L.M., Vinks, A., Reid, J.M., Ahern, C.H., Thomas, G., Mercer, C., Krueger, D.A., Houghton, P., Doyle, A., Chen, H., Weigel, B.J., Blaney, S.M. (2015) A Phase I Study of Cixutumumab (IMC-A12) in Combination with Temsirolimus (CCI-779) in Children with Recurrent Solid Tumors: A Children's Oncology Group Phase 1 Consortium Report. Clinical Cancer Research, Apr 1;21(7):1558-65.  doi: 10.1158/1078-0432.CCR-14-0595. Epub 2014 Dec 2.   
 
Um, S. H., Sticker-Jantscheff, M., Chau, G. C., Vintersten, K., Mueller, M., Gangloff, Y. G., Adams, R.H., Spetz, J.-F., Elghazi, L., Pfluger, P.T., Pende M., Bernal-Mizrachi E., Tauler, A., Tschöp, M.H., Thomas, G. and Kozma S.C. (2015) S6K1 controls pancreatic β cell size independently of intrauterine growth restriction.J Clin Invest. 2015 Jul 1;125(7):2736-47. doi: 10.1172/JCI77030.
 
Pardo V, González-Rodríguez Á, Muntané J, Kozma SC, Valverde ÁM. (2015) Role of hepatocyte S6K1 in palmitic acid-induced endoplasmic reticulum stress, lipotoxicity, insulin resistance and in oleic acid-induced protection. Food Chem Toxicol. 2015 Jun;80:298-309. doi: 10.1016/j.fct.2015.03.029.
 
Meo-Evoli N, Almacellas E, Massucci F.A., Gentilella A., Ambrosio S, Kozma SC, Thomas G, and Tauler A. (2015) V-ATPase, a master effector of E2F1-mediated lysosomal trafficking, mTORC1 activation and autophagy. Oncotarget, Sep 29;6(29):28057-70
 
Cortés CKozma SCTauler A, Ambrosio S. (2015) MYCN concurrence with SAHA-induced cell death in human neuroblastoma cells. Cell Oncol (Dordr). 2015 Aug 26:38:341–352.
 
Gentilella A, Kozma SC, Thomas G. (2015) A liaison between mTOR signaling, ribosome biogenesis and cancer. Biochim Biophys Acta. 2015 Jul;1849(7):812-820. doi: 10.1016/j.bbagrm.2015.02.005. Epub 2015 Feb 28. Review. 
 
2014


Bursac S, Brdovcak MC, Donati G, Volarevic S. (2014)  Activation of the tumor suppressor p53 upon impairment of ribosome biogenesis. REVIEW. Biochimica et Biophysica Acta.Jun;1842(6):817-30.
 
 
 
2013
 
Donati, G., Peddigari, S., Mercer, C. A., Thomas, G. (2013) 5S rRNA is an essential component of a nascent ribosomal precursor complex that regulates the Hdm2-p53 checkpoint. Cell ReportsJul 11; 4 (1): 87-98.    
 
Teng, T., Mercer C. A., Hexley, P., Thomas, G (*)., Fumagalli, S. (2013) Loss of tumor suppressors RPL5/RPL11 does not induce cell cycle arrest, but impedes proliferation due to reduced ribosome content and translation capacity. Mol Cell Biol, 33 (23): 4660-71. Spotlighted Article (*) corresponding author
 
Zhu Y, Pires KM, Whitehead KJ, Olsen CD, Wayment B, Zhang YC, Bugger H, Ilkun O, Litwin SE, Thomas G, Kozma SC, Abel ED. (2013) Mechanistic target of rapamycin (Mtor) is essential for murine embryonic heart development and growth. PLoS One. 2013;8(1):e54221.
 
Guo F, Zhang S, Grogg M, Cancelas JA, Varney ME, Starczynowski DT, Du W, Yang JQ, Liu W, Zhu W, Thomas G, Kozma S, Pang Q, Zheng Y. (2013) Mouse gene targeting reveals an essential role of mTOR in hematopoietic stem cell engraftment and hematopoiesis. Haematologica. May 28. Sep;98(9):1353-8.            
 
Guo F, Li J, Du W, Zhang S, O'Connor M, Thomas G, Kozma S, Zingarelli B, Pang Q, Zheng Y. (2013) mTOR regulates DNA damage response through NF-κB-mediated FANCD2 pathway in hematopoietic cells. Leukemia. Leukemia. 2013 Oct;27(10):2040-6.
 
Teng T, Thomas G, Mercer CA. (2013) Growth control and ribosomopathies. Curr Opin Genet Dev. Feb; 23(1):63-71  Review.
 
Muñoz-Pinedo C, González-Suárez E, Portela A, Gentilella A, Esteller M. (2013) Exploiting tumor vulnerabilities: epigenetics, cancer metabolism and the mTOR pathway in the era of personalized medicine. Cancer Res. (2013  2013 Jul 15;73(14):4185-9.
 
 
2012
 
Thomas, H. E., Mercer, C. A., Carnevalli, L. S., Park, J., Andersen, J. B., Conner, E. A., Tanaka, K., Matsutani, T., Iwanami, A., Aronow, B. J., Manway, L., Maira, S. M., Thorgeirsson, S. S., Mischel, P. S., Thomas, G., and Kozma, S. C. (2012) mTOR Inhibitors Synergize on Regression, Reversal of Gene Expression, and Autophagy in Hepatocellular Carcinoma, Science Translational Medicine4, 139ra84 Commentary, Nature 485, 50. 
 
Fumagalli, S., Ivanenkov, V. V., Teng., T. ,Thomas, G .Supra-induction of p53 by Disruption of 40S and 60S Ribosome Biogenesis leads to the Activation of a Novel G2/M Checkpoint, Genes and Development, 26, 1028-40
 
Francisco R, Pérez-Perarnau A, Cortés C, Gil J, Tauler A, Ambrosio S. (2012) Histone deacetylase inhibition induces apoptosis and autophagy in human neuroblastoma cells.Cancer Lett. 2012 May 1;318(1):42-52. doi: 10.1016/j.canlet.2011.11.036. Epub 2011 Dec 17.
 
Espada L, Meo-Evoli N, Sancho P, Real S, Fabregat I, Ambrosio S, Tauler A. (2012) ROS production is essential for the apoptotic function of E2F1 in pheochromocytoma and neuroblastoma cell lines. PLoS One. 2012;7(12):e51544. doi: 10.1371/journal.pone.0051544. Epub 2012 Dec 12.
 
Piguet AC, Martins PJ, Kozma SC (2012) Rapamycin impacts positively on longevity, despite glucose intolerance induction. J Hepatol. 57:1368-9
 
Castañeda TR, Abplanalp W, Um SH, Pfluger PT, Schrott B, Brown K, Grant E, Carnevalli L, Benoit SC, Morgan DA, Gilham D, Hui DY, Rahmouni K, Thomas G, Kozma SC, Clegg DJ, Tschöp MH.  (2012) Metabolic control by S6 kinases depends on dietary lipids. PLoS One.7(3):e32631.
 
Tschöp MH, Speakman JR, Arch JR, Auwerx J, Brüning JC, Chan L, Eckel RH, Farese RV Jr, Galgani JE, Hambly C, Herman MA, Horvath TL, Kahn BB, Kozma SC, Maratos-Flier E, Müller TD, Münzberg H, Pfluger PT, Plum L, Reitman ML, Rahmouni K, Shulman GI, Thomas G, Kahn CR, Ravussin E.(2012) A guide to analysis of mouse energy metabolism. Nat Methods. Dec 28;9(1):57-63.
 
Donati G, Thomas G. (2012) Apoptosis in pluripotent stem cells: RPL11 strikes again. Cell Cycle, 11, 840.  Editorial.
 
Gentilella, A., and Thomas, G. (2012) Cancer biology: The director's cut, Nature 485, 50-51. Editorial
 
Teng, T., and Thomas, G., (Eds.) (2012) Ribosome Biogenesis, Cell Cycle Checkpoints and Cancer Progression, Chartridge Books Oxford, Oxford, England. Editorial
 

Wiczer, B. M., and Thomas, G. (2012) Phospholipase D and mTORC1: nutrients are what bring them together, Science signaling 5, pe13. Editorial 

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