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Christian   Frezza

Christian Frezza

Education

Ph.D. in Neurobiology,  School of Biosciences, University of Padova, Italy

Current position

Programme Leader Track, MRC Cancer Unit, University of Cambridge, UK 

Publications (since 2013)

  1. Sciacovelli, M., Goncalves, E., Johnson, T. I., Zecchini, V. R., da Costa, A. S., Gaude, E., Drubbel, A. V., Theobald, S. J., Abbo, S. R., Tran, M. G., Rajeeve, V., Cardaci, S., Foster, S., Yun, H., Cutillas, P., Warren, A., Gnanapragasam, V., Gottlieb, E., Franze, K., Huntly, B., Maher, E. R., Maxwell, P. H., Saez-Rodriguez, J. and Frezza, C. (2016). Fumarate is an epigenetic modifier that elicits epithelial-to-mesenchymal transition. Nature 537(7621): 544-547.

  2. Gammage, P. A., Gaude, E., Van Haute, L., Rebelo-Guiomar, P., Jackson, C. B., Rorbach, J., Pekalski, M. L., Robinson, A. J., Charpentier, M., Concordet, J. P., Frezza, C. and Minczuk, M. (2016). Near-complete elimination of mutant mtDNA by iterative or dynamic dose-controlled treatment with mtZFNs. Nucleic Acids Res 44(16): 7804-7816.

  3. Schurich, A., Pallett, L. J., Jajbhay, D., Wijngaarden, J., Otano, I., Gill, U. S., Hansi, N., Kennedy, P. T., Nastouli, E., Gilson, R., Frezza, C., Henson, S. M. and Maini, M. K. (2016). Distinct Metabolic Requirements of Exhausted and Functional Virus-Specific CD8 T Cells in the Same Host. Cell Rep 16(5): 1243-1252.

  4. Pell, V. R., Chouchani, E. T., Frezza, C., Murphy, M. P. and Krieg, T. (2016). Succinate metabolism: a new therapeutic target for myocardial reperfusion injury. Cardiovasc Res 111(2): 134-141.

  5. Frezza, C. (2016). Cancer metabolism: Addicted to serine. Nat Chem Biol 12(6): 389-390.

  6. Sciacovelli, M. and Frezza, C. (2016). Oncometabolites: Unconventional triggers of oncogenic signalling cascades. Free Radic Biol Med.

  7. Burrows, N., Cane, G., Robson, M., Gaude, E. J., Howat, W., Szlosarek, P. W., Pedley, R. B., Frezza, C., Ashcroft, M. and Maxwell, P. H. (2016). Hypoxia-induced nitric oxide production and tumour perfusion is inhibited by pegylated arginine deiminase (ADI-PEG20). Sci Rep 14(6): 22950.

  8. Kerr, E. M., Gaude, E., Turrell, F. K., Frezza, C. and Martins, C. P. (2016). Mutant Kras copy number defines metabolic reprogramming and therapeutic susceptibilities. Nature 531(7592): 110-113.

  9. Chouchani, E. T., Pell, V. R., James, A. M., Work, L. M., Saeb-Parsy, K., Frezza, C., Krieg, T. and Murphy, M. P. (2016). A Unifying Mechanism for Mitochondrial Superoxide Production during Ischemia-Reperfusion Injury. Cell Metab 23(2): 254-263.

  10. Koziol, M. J., Bradshaw, C. R., Allen, G. E., Costa, A. S., Frezza, C. and Gurdon, J. B. (2016). Identification of methylated deoxyadenosines in vertebrates reveals diversity in DNA modifications. Nat Struct Mol Biol 23(1): 24-30.

  11. Rodenhizer, D., Gaude, E., Cojocari, D., Mahadevan, R., Frezza, C., Wouters, B. G. and McGuigan, A. P. (2016). A three-dimensional engineered tumour for spatial snapshot analysis of cell metabolism and phenotype in hypoxic gradients. Nat Mater 15(2): 227-234.

  12. Block, K. I., Gyllenhaal, C., Lowe, L., Amedei, A., Amin, A. R., Amin, A., Aquilano, K., Arbiser, J., Arreola, A., Arzumanyan, A., Ashraf, S. S., Azmi, A. S., Benencia, F., Bhakta, D., Bilsland, A., Bishayee, A., Blain, S. W., Block, P. B., Boosani, C. S., Carey, T. E., Carnero, A., Carotenuto, M., Casey, S. C., Chakrabarti, M., Chaturvedi, R., Chen, G. Z., Chen, H., Chen, S., Chen, Y. C., Choi, B. K., Ciriolo, M. R., Coley, H. M., Collins, A. R., Connell, M., Crawford, S., Curran, C. S., Dabrosin, C., Damia, G., Dasgupta, S., DeBerardinis, R. J., Decker, W. K., Dhawan, P., Diehl, A. M., Dong, J. T., Dou, Q. P., Drew, J. E., Elkord, E., El-Rayes, B., Feitelson, M. A., Felsher, D. W., Ferguson, L. R., Fimognari, C., Firestone, G. L., Frezza, C., Fujii, H., Fuster, M. M., Generali, D., Georgakilas, A. G., Gieseler, F., Gilbertson, M., Green, M. F., Grue, B., Guha, G., Halicka, D., Helferich, W. G., Heneberg, P., Hentosh, P., Hirschey, M. D., Hofseth, L. J., Holcombe, R. F., Honoki, K., Hsu, H. Y., Huang, G. S., Jensen, L. D., Jiang, W. G., Jones, L. W., Karpowicz, P. A., Keith, W. N., Kerkar, S. P., Khan, G. N., Khatami, M., Ko, Y. H., Kucuk, O., Kulathinal, R. J., Kumar, N. B., Kwon, B. S., Le, A., Lea, M. A., Lee, H. Y., Lichtor, T., Lin, L. T., Locasale, J. W., Lokeshwar, B. L., Longo, V. D., Lyssiotis, C. A., MacKenzie, K. L., Malhotra, M., Marino, M., Martinez-Chantar, M. L., Matheu, A., Maxwell, C., McDonnell, E., Meeker, A. K., Mehrmohamadi, M., Mehta, K., Michelotti, G. A., Mohammad, R. M., Mohammed, S. I., Morre, D. J., Muralidhar, V., Muqbil, I., Murphy, M. P., Nagaraju, G. P., Nahta, R., Niccolai, E., Nowsheen, S., Panis, C., Pantano, F., Parslow, V. R., Pawelec, G., Pedersen, P. L., Poore, B., Poudyal, D., Prakash, S., Prince, M., Raffaghello, L., Rathmell, J. C., Rathmell, W. K., Ray, S. K., Reichrath, J., Rezazadeh, S., Ribatti, D., Ricciardiello, L., Robey, R. B., Rodier, F., Rupasinghe, H. P., Russo, G. L., Ryan, E. P., Samadi, A. K., Sanchez-Garcia, I., Sanders, A. J., Santini, D., Sarkar, M., Sasada, T., Saxena, N. K., Shackelford, R. E., Shantha Kumara, H. M., Sharma, D., Shin, D. M., Sidransky, D., Siegelin, M. D., Signori, E., Singh, N., Sivanand, S., Sliva, D., Smythe, C., Spagnuolo, C., Stafforini, D. M., Stagg, J., Subbarayan, P. R., Sundin, T., Talib, W. H., Thompson, S. K., Tran, P. T., Ungefroren, H., Vander Heiden, M. G., Venkateswaran, V., Vinay, D. S., Vlachostergios, P. J., Wang, Z., Wellen, K. E., Whelan, R. L., Yang, E. S., Yang, H., Yang, X., Yaswen, P., Yedjou, C., Yin, X., Zhu, J. and Zollo, M. (2015). Designing a broad-spectrum integrative approach for cancer prevention and treatment. Semin Cancer Biol 35 Suppl: S276-304.

  13. Hirschey, M. D., DeBerardinis, R. J., Diehl, A. M., Drew, J. E., Frezza, C., Green, M. F., Jones, L. W., Ko, Y. H., Le, A., Lea, M. A., Locasale, J. W., Longo, V. D., Lyssiotis, C. A., McDonnell, E., Mehrmohamadi, M., Michelotti, G., Muralidhar, V., Murphy, M. P., Pedersen, P. L., Poore, B., Raffaghello, L., Rathmell, J. C., Sivanand, S., Vander Heiden, M. G., Wellen, K. E. and Target Validation, T. (2015). Dysregulated metabolism contributes to oncogenesis. Semin Cancer Biol 35 Suppl: S129-150.

  14. Matheson, N. J., Sumner, J., Wals, K., Rapiteanu, R., Weekes, M. P., Vigan, R., Weinelt, J., Schindler, M., Antrobus, R., Costa, A. S., Frezza, C., Clish, C. B., Neil, S. J. and Lehner, P. J. (2015). Cell Surface Proteomic Map of HIV Infection Reveals Antagonism of Amino Acid Metabolism by Vpu and Nef. Cell Host Microbe 18(4): 409-423.

  15. Catanzaro, D., Gaude, E., Orso, G., Giordano, C., Guzzo, G., Rasola, A., Ragazzi, E., Caparrotta, L., Frezza, C. and Montopoli, M. (2015). Inhibition of glucose-6-phosphate dehydrogenase sensitizes cisplatin-resistant cells to death. Oncotarget 6(30): 30102-30114.

  16. Frezza, C. and Mauro, C. (2015). Editorial: The Metabolic Challenges of Immune Cells in Health and Disease. Front Immunol 6: 293.

  17. Tannahill, G. M., Iraci, N., Gaude, E., Frezza, C. and Pluchino, S. (2015). Metabolic reprograming of mononuclear phagocytes in progressive multiple sclerosis. Front Immunol 6: 106.

  18. Buescher, J. M., Antoniewicz, M. R., Boros, L. G., Burgess, S. C., Brunengraber, H., Clish, C. B., DeBerardinis, R. J., Feron, O., Frezza, C., Ghesquiere, B., Gottlieb, E., Hiller, K., Jones, R. G., Kamphorst, J. J., Kibbey, R. G., Kimmelman, A. C., Locasale, J. W., Lunt, S. Y., Maddocks, O. D., Malloy, C., Metallo, C. M., Meuillet, E. J., Munger, J., Noh, K., Rabinowitz, J. D., Ralser, M., Sauer, U., Stephanopoulos, G., St-Pierre, J., Tennant, D. A., Wittmann, C., Vander Heiden, M. G., Vazquez, A., Vousden, K., Young, J. D., Zamboni, N. and Fendt, S. M. (2015). A roadmap for interpreting (13)C metabolite labeling patterns from cells. Curr Opin Biotechnol 34: 189-201.

  19. Zheng, L., Cardaci, S., Jerby, L., MacKenzie, E. D., Sciacovelli, M., Johnson, T. I., Gaude, E., King, A., Leach, J. D., Edrada-Ebel, R., Hedley, A., Morrice, N. A., Kalna, G., Blyth, K., Ruppin, E., Frezza, C. and Gottlieb, E. (2015). Fumarate induces redox-dependent senescence by modifying glutathione metabolism. Nat Commun 6: 6001.

  20. Patella, F., Schug, Z. T., Persi, E., Neilson, L. J., Erami, Z., Avanzato, D., Maione, F., Hernandez-Fernaud, J. R., Mackay, G., Zheng, L., Reid, S., Frezza, C., Giraudo, E., Fiorio Pla, A., Anderson, K., Ruppin, E., Gottlieb, E. and Zanivan, S. (2015). Proteomics-based metabolic modeling reveals that fatty acid oxidation (FAO) controls endothelial cell (EC) permeability. Mol Cell Proteomics 14(3): 621-634.

  21. Chouchani, E. T., Pell, V. R., Gaude, E., Aksentijevic, D., Sundier, S. Y., Robb, E. L., Logan, A., Nadtochiy, S. M., Ord, E. N., Smith, A. C., Eyassu, F., Shirley, R., Hu, C. H., Dare, A. J., James, A. M., Rogatti, S., Hartley, R. C., Eaton, S., Costa, A. S., Brookes, P. S., Davidson, S. M., Duchen, M. R., Saeb-Parsy, K., Shattock, M. J., Robinson, A. J., Work, L. M., Frezza, C., Krieg, T. and Murphy, M. P. (2014). Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS. Nature 515(7527): 431-435.

  22. Yizhak, K., Gaude, E., Le Devedec, S., Waldman, Y. Y., Stein, G. Y., van de Water, B., Frezza, C. and Ruppin, E. (2014). Phenotype-based cell-specific metabolic modeling reveals metabolic liabilities of cancer. Elife 3.

  23. Yizhak, K., Le Devedec, S. E., Rogkoti, V. M., Baenke, F., de Boer, V. C., Frezza, C., Schulze, A., van de Water, B. and Ruppin, E. (2014). A computational study of the Warburg effect identifies metabolic targets inhibiting cancer migration. Mol Syst Biol 10: 744.

  24. Gaude, E. and Frezza, C. (2014). Defects in mitochondrial metabolism and cancer. Cancer Metab 2: 10.

  25. Clark, G. R., Sciacovelli, M., Gaude, E., Walsh, D. M., Kirby, G., Simpson, M. A., Trembath, R. C., Berg, J. N., Woodward, E. R., Kinning, E., Morrison, P. J., Frezza, C. and Maher, E. R. (2014). Germline FH mutations presenting with pheochromocytoma. J Clin Endocrinol Metab 99(10): E2046-2050.

  26. Sciacovelli, M., Gaude, E., Hilvo, M. and Frezza, C. (2014). The metabolic alterations of cancer cells. Methods Enzymol 542: 1-23.

  27. Zecchini, V., Madhu, B., Russell, R., Pertega-Gomes, N., Warren, A., Gaude, E., Borlido, J., Stark, R., Ireland-Zecchini, H., Rao, R., Scott, H., Boren, J., Massie, C., Asim, M., Brindle, K., Griffiths, J., Frezza, C., Neal, D. E. and Mills, I. G. (2014). Nuclear ARRB1 induces pseudohypoxia and cellular metabolism reprogramming in prostate cancer. EMBO J 33(12): 1365-1382.

  28. Boettcher, M., Lawson, A., Ladenburger, V., Fredebohm, J., Wolf, J., Hoheisel, J. D., Frezza, C. and Shlomi, T. (2014). High throughput synthetic lethality screen reveals a tumorigenic role of adenylate cyclase in fumarate hydratase-deficient cancer cells. BMC Genomics 15: 158.

  29. Frezza, C. (2014). The role of mitochondria in the oncogenic signal transduction. Int J Biochem Cell Biol 48: 11-17.

  30. Allen, M. D., Luong, P., Hudson, C., Leyton, J., Delage, B., Ghazaly, E., Cutts, R., Yuan, M., Syed, N., Lo Nigro, C., Lattanzio, L., Chmielewska-Kassassir, M., Tomlinson, I., Roylance, R., Whitaker, H. C., Warren, A. Y., Neal, D., Frezza, C., Beltran, L., Jones, L. J., Chelala, C., Wu, B. W., Bomalaski, J. S., Jackson, R. C., Lu, Y. J., Crook, T., Lemoine, N. R., Mather, S., Foster, J., Sosabowski, J., Avril, N., Li, C. F. and Szlosarek, P. W. (2014). Prognostic and therapeutic impact of argininosuccinate synthetase 1 control in bladder cancer as monitored longitudinally by PET imaging. Cancer Res 74(3): 896-907.

  31. Cogliati, S., Frezza, C., Soriano, M. E., Varanita, T., Quintana-Cabrera, R., Corrado, M., Cipolat, S., Costa, V., Casarin, A., Gomes, L. C., Perales-Clemente, E., Salviati, L., Fernandez-Silva, P., Enriquez, J. A. and Scorrano, L. (2013). Mitochondrial cristae shape determines respiratory chain supercomplexes assembly and respiratory efficiency. Cell 155(1): 160-171.

  32. Sciacovelli, M., Guzzo, G., Morello, V., Frezza, C., Zheng, L., Nannini, N., Calabrese, F., Laudiero, G., Esposito, F., Landriscina, M., Defilippi, P., Bernardi, P. and Rasola, A. (2013). The mitochondrial chaperone TRAP1 promotes neoplastic growth by inhibiting succinate dehydrogenase. Cell Metab 17(6): 988-999.

  33. Zheng, L., Mackenzie, E. D., Karim, S. A., Hedley, A., Blyth, K., Kalna, G., Watson, D. G., Szlosarek, P., Frezza, C. and Gottlieb, E. (2013). Reversed argininosuccinate lyase activity in fumarate hydratase-deficient cancer cells. Cancer Metab 1(1): 12.

  34. Tannahill, G. M., Curtis, A. M., Adamik, J., Palsson-McDermott, E. M., McGettrick, A. F., Goel, G., Frezza, C., Bernard, N. J., Kelly, B., Foley, N. H., Zheng, L., Gardet, A., Tong, Z., Jany, S. S., Corr, S. C., Haneklaus, M., Caffrey, B. E., Pierce, K., Walmsley, S., Beasley, F. C., Cummins, E., Nizet, V., Whyte, M., Taylor, C. T., Lin, H., Masters, S. L., Gottlieb, E., Kelly, V. P., Clish, C., Auron, P. E., Xavier, R. J. and O'Neill, L. A. (2013). Succinate is an inflammatory signal that induces IL-1beta through HIF-1alpha. Nature 496(7444): 238-242.

Protocols by Christian Frezza
  1. Identification of Methylated Deoxyadenosines in Genomic DNA by dA6m DNA Immunoprecipitation