Photo of Othon Iliopoulos,  MD

Othon Iliopoulos, MD

Massachusetts General Hospital

Massachusetts General Hospital
Phone: (617) 724-3404
Fax: (617) 724-9648

Othon Iliopoulos, MD

Massachusetts General Hospital


  • Associate Professor, Medicine, Harvard Medical School
  • Associate Professor of Medicine, Ceneter for Cancer Research, Massachusetts General Hospital



  • Member, Center Scientific Council

Research Abstract

My laboratory is interested in the biology of tumor suppressor genes with particular emphasis on the von Hippel-Lindau tumor suppressor protein. This protein is a substrate receptor for the SCFVHL E3 ligase and induces tumor suppression, at least in part, by regulating the expression of hypoxia-inducible genes. A bona fide target of this complex is hypoxia-inducible factor HIF. We are currently exploring potential therapeutic implications of this known VHL-HIF interaction and, in addition, we are identifying novel substrates, which are ubiquitinated by the SCFVHL E3 ligase complex. At the clinical front we are creating a multidisciplinary VHL/Familial Renal Carcinoma clinic, staffed with professional genetic counselors and operating under the auspices of the MGH Cancer Genetics Program. We plan to co-ordinate patient care and approach the current questions regarding VHL disease monitoring, chemoprevention and timely intervention on a protocol-based manner. We also hope to enroll VHL patients in suitable treatment protocols.


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  • Laviolette LA, Mermoud J, Calvo IA, Olson N, Boukhali M, Steinlein OK, Roider E, Sattler EC, Huang D, Teh BT, Motamedi M, Haas W, Iliopoulos O. Negative regulation of EGFR signalling by the human folliculin tumour suppressor protein. Nat Commun 2017; 8:15866. PubMed
  • Schneider M, Dinkelborg K, Xiao X, Chan-Smutko G, Hruska K, Huang D, Sagar P, Harisinghani M, Iliopoulos O. Early onset renal cell carcinoma in an adolescent girl with germline FLCN exon 5 deletion. Fam Cancer 2017. PubMed
  • Okazaki A, Gameiro PA, Christodoulou D, Laviollette L, Schneider M, Chaves F, Stemmer-Rachamimov A, Yazinski SA, Lee R, Stephanopoulos G, Zou L, Iliopoulos O. Glutaminase and poly(ADP-ribose) polymerase inhibitors suppress pyrimidine synthesis and VHL-deficient renal cancers. J Clin Invest 2017. PubMed
  • Salas-Vega S, Iliopoulos O, Mossialos E. Assessment of Overall Survival, Quality of Life, and Safety Benefits Associated With New Cancer Medicines. JAMA Oncol 2016. PubMed
  • Noonan HR, Metelo AM, Kamei CN, Peterson RT, Drummond IA, Iliopoulos O. Loss of vhl in the zebrafish pronephros recapitulates early stages of human clear cell renal cell carcinoma. Dis Model Mech 2016; 9:873-84. PubMed
  • Keibler MA, Wasylenko TM, Kelleher JK, Iliopoulos O, Vander Heiden MG, Stephanopoulos G. Metabolic requirements for cancer cell proliferation. Cancer Metab 2016; 4:16. PubMed
  • Metelo AM, Noonan H, Iliopoulos O. HIF2a inhibitors for the treatment of VHL disease. 2015; 6:23036-7. PubMed
  • Gbormittah FO, Bones J, Hincapie M, Tousi F, Hancock WS, Iliopoulos O. Clusterin glycopeptide variant characterization reveals significant site-specific glycan changes in the plasma of clear cell renal cell carcinoma. J Proteome Res 2015. PubMed
  • Black JC, Atabakhsh E, Kim J, Biette KM, Van Rechem C, Ladd B, Burrowes PD, Donado C, Mattoo H, Kleinstiver BP, Song B, Andriani G, Joung JK, Iliopoulos O, Montagna C, Pillai S, Getz G, Whetstine JR. Hypoxia drives transient site-specific copy gain and drug-resistant gene expression. Genes Dev 2015; 29:1018-31. PubMed
  • Metelo AM, Noonan HR, Li X, Jin Y, Baker R, Kamentsky L, Zhang Y, van Rooijen E, Shin J, Carpenter AE, Yeh JR, Peterson RT, Iliopoulos O. Pharmacological HIF2α inhibition improves VHL disease-associated phenotypes in zebrafish model. J Clin Invest 2015; 125:1987-97. PubMed
  • Gbormittah FO, Lee LY, Taylor K, Hancock WS, Iliopoulos O. Comparative studies of the proteome, glycoproteome, and N-glycome of clear cell renal cell carcinoma plasma before and after curative nephrectomy. J Proteome Res 2014. PubMed
  • Gameiro PA, Laviolette LA, Kelleher JK, Iliopoulos O, Stephanopoulos G. Cofactor balance by nicotinamide nucleotide transhydrogenase (NNT) coordinates reductive carboxylation and glucose catabolism in the tricarboxylic acid (TCA) cycle. J Biol Chem 2013. PubMed
  • Gameiro PA, Yang J, Metelo AM, Pérez-Carro R, Baker R, Wang Z, Arreola A, Rathmell WK, Olumi A, López-Larrubia P, Stephanopoulos G, Iliopoulos O. In vivo HIF-mediated reductive carboxylation is regulated by citrate levels and sensitizes VHL-deficient cells to glutamine deprivation. Cell Metab 2013; 17:372-85. PubMed
  • Nicolay BN, Gameiro PA, Tschöp K, Korenjak M, Heilmann AM, Asara JM, Stephanopoulos G, Iliopoulos O, Dyson NJ. Loss of RBF1 changes glutamine catabolism. Genes Dev 2013; 27:182-96. PubMed
  • Laviolette LA, Wilson J, Koller J, Neil C, Hulick P, Rejtar T, Karger B, Teh BT, Iliopoulos O. Human folliculin delays cell cycle progression through late S and G2/M-phases: effect of phosphorylation and tumor associated mutations. PLoS ONE 2013; 8:e66775. PubMed
  • Tousi F, Bones J, Iliopoulos O, Hancock WS, Hincapie M. Multidimensional liquid chromatography platform for profiling alterations of clusterin N-glycosylation in the plasma of patients with renal cell carcinoma. J Chromatogr A 2012; 1256:121-8. PubMed
  • Rafalko A, Iliopoulos O, Fusaro VA, Hancock W, Hincapie M. Immunoaffinity Enrichment and Liquid Chromatography-Selected Reaction Monitoring Mass Spectrometry for Quantitation of Carbonic Anhydrase 12 in Cultured Renal Carcinoma Cells. Anal Chem 2010. PubMed
  • Zimmer M, Lamb J, Ebert BL, Lynch M, Neil C, Schmidt E, Golub TR, Iliopoulos O. The connectivity map links iron regulatory protein-1-mediated inhibition of hypoxia-inducible factor-2a translation to the anti-inflammatory 15-deoxy-delta12,14-prostaglandin J2. Cancer Res 2010; 70:3071-9. PubMed
  • Zhong L, D'Urso A, Toiber D, Sebastian C, Henry RE, Vadysirisack DD, Guimaraes A, Marinelli B, Wikstrom JD, Nir T, Clish CB, Vaitheesvaran B, Iliopoulos O, Kurland I, Dor Y, Weissleder R, Shirihai OS, Ellisen LW, Espinosa JM, Mostoslavsky R. The histone deacetylase Sirt6 regulates glucose homeostasis via Hif1alpha. Cell 2010; 140:280-93. PubMed
  • Zimmer M,Ebert BL,Neil C,Brenner K,Papaioannou I,Melas A,Tolliday N,Lamb J,Pantopoulos K,Golub T,Iliopoulos O. Small-molecule inhibitors of HIF-2a translation link its 5'UTR iron-responsive element to oxygen sensing. Mol Cell 2008; 32:838-48. PubMed
  • Bhatt RS, Landis DM, Zimmer M, Torregrossa J, Chen S, Sukhatme VP, Iliopoulos O, Balk S, Bubley GJ. Hypoxia-inducible factor-2alpha: effect on radiation sensitivity and differential regulation by an mTOR inhibitor. BJU Int 2008; 102:358-63. PubMed
  • Michaelson MD,Iliopoulos O,McDermott DF,McGovern FJ,Harisinghani MG,Oliva E. Case records of the Massachusetts General Hospital. Case 17-2008. A 63-year-old man with metastatic renal-cell carcinoma. N Engl J Med 2008; 358:2389-96. PubMed
  • Iliopoulos O. Molecular biology of renal cell cancer and the identification of therapeutic targets. J Clin Oncol 2006; 24:5593-600. PubMed
  • Mizukami Y, Jo WS, Duerr EM, Gala M, Li J, Zhang X, Zimmer MA, Iliopoulos O, Zukerberg LR, Kohgo Y, Lynch MP, Rueda BR, Chung DC. Induction of interleukin-8 preserves the angiogenic response in HIF-1alpha-deficient colon cancer cells. Nat Med 2005; 11:992-7. PubMed
  • Atkins MB, Avigan DE, Bukowski RM, Childs RW, Dutcher JP, Eisen TG, Figlin RA, Finke JH, Flanigan RC, George DJ, Goldberg SN, Gordon MS, Iliopoulos O, Kaelin WG, Linehan WM, Lipton A, Motzer RJ, Novick AC, Stadler WM, Teh BT, Yang JC, King L. Innovations and challenges in renal cancer: consensus statement from the first international conference. Clin Cancer Res 2004; 10:6277S-81S. PubMed
  • Hulick P, Zimmer M, Margulis V, Skates S, Hamel M, Dahl DM, Michaelson DM, Libermann T, Signoretti S, Carney W, Wood C, Iliopoulos O. Blood Levels of Carbonic Anhydrase 9 Correlate with Clear Cell Renal Cell Carcinoma Activity Clin. Proteomics 2009; 5:37-45.