Photo of Othon Iliopoulos,  MD

Othon Iliopoulos, MD

Massachusetts General Hospital

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


iliopoul@helix.mgh.harvard.edu

Othon Iliopoulos, MD

Massachusetts General Hospital

EDUCATIONAL TITLES

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

DF/HCC PROGRAM AFFILIATION

DF/HCC ASSOCIATIONS

  • 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.

Publications

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  • 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 HIF2留 inhibition improves VHL disease-associated phenotypes in zebrafish model. J Clin Invest 2015; 125:1987-97. 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
  • 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 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
  • Mizukami Y, Li J, Zhang X, Zimmer MA, Iliopoulos O, Chung DC. Hypoxia-inducible factor-1-independent regulation of vascular endothelial growth factor by hypoxia in colon cancer. Cancer Res 2004; 64:1765-72. PubMed
  • Zimmer M, Doucette D, Siddiqui N, Iliopoulos O. Inhibition of hypoxia-inducible factor is sufficient for growth suppression of VHL-/- tumors. Mol Cancer Res 2004; 2:89-95. PubMed
  • Iliopoulos O. von Hippel-Lindau disease: genetic and clinical observations. Front Horm Res 2001; 28:131-66. 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.
  • Kamura T, Koepp DM, Conrad MN, Skowyra D, Moreland RJ, Iliopoulos O, Lane WS, Kaelin WG, Elledge SJ, Conaway RC, Harper JW, Conaway JW. Rbx1, a component of the VHL tumor suppressor complex and SCF ubiquitin ligase. Science 1999; 284:657-61. PubMed
  • Lieubeau-Teillet B, Rak J, Jothy S, Iliopoulos O, Kaelin W, Kerbel RS. von Hippel-Lindau gene-mediated growth suppression and induction of differentiation in renal cell carcinoma cells grown as multicellular tumor spheroids. Cancer Res 1998; 58:4957-62. PubMed
  • Iliopoulos O, Ohh M, Kaelin WG. pVHL19 is a biologically active product of the von Hippel-Lindau gene arising from internal translation initiation. Proc Natl Acad Sci U S A 1998; 95:11661-6. PubMed
  • Ohh M, Yauch RL, Lonergan KM, Whaley JM, Stemmer-Rachamimov AO, Louis DN, Gavin BJ, Kley N, Kaelin WG, Iliopoulos O. The von Hippel-Lindau tumor suppressor protein is required for proper assembly of an extracellular fibronectin matrix. Mol Cell 1998; 1:959-68. PubMed
  • Lonergan KM, Iliopoulos O, Ohh M, Kamura T, Conaway RC, Conaway JW, Kaelin WG. Regulation of hypoxia-inducible mRNAs by the von Hippel-Lindau tumor suppressor protein requires binding to complexes containing elongins B/C and Cul2. Mol Cell Biol 1998; 18:732-41. PubMed
  • Iliopoulos O, Kaelin WG. The molecular basis of von Hippel-Lindau disease. Mol Med 1997; 3:289-93. PubMed
  • Corless CL, Kibel AS, Iliopoulos O, Kaelin WG. Immunostaining of the von Hippel-Lindau gene product in normal and neoplastic human tissues. Hum Pathol 1997; 28:459-64. PubMed
  • Iliopoulos O, Levy AP, Jiang C, Kaelin WG, Goldberg MA. Negative regulation of hypoxia-inducible genes by the von Hippel-Lindau protein. Proc Natl Acad Sci U S A 1996; 93:10595-9. PubMed
  • Kibel A, Iliopoulos O, DeCaprio JA, Kaelin WG. Binding of the von Hippel-Lindau tumor suppressor protein to Elongin B and C. Science 1995; 269:1444-6. PubMed
  • Iliopoulos O, Kibel A, Gray S, Kaelin WG. Tumour suppression by the human von Hippel-Lindau gene product. Nat Med 1995; 1:822-6. PubMed
  • Wen SF, Parthasarathy R, Iliopoulos O, Oberley TD. Acute renal failure following binge drinking and nonsteroidal antiinflammatory drugs. Am J Kidney Dis 1992; 20:281-5. PubMed
  • Iliopoulos O, Baroody FM, Naclerio RM, Bochner BS, Kagey-Sobotka A, Lichtenstein LM. Histamine-containing cells obtained from the nose hours after antigen challenge have functional and phenotypic characteristics of basophils. J Immunol 1992; 148:2223-8. PubMed
  • Iliopoulos O, Proud D, Adkinson NF, Creticos PS, Norman PS, Kagey-Sobotka A, Lichtenstein LM, Naclerio RM. Effects of immunotherapy on the early, late, and rechallenge nasal reaction to provocation with allergen: changes in inflammatory mediators and cells. J Allergy Clin Immunol 1991; 87:855-66. PubMed
  • Iliopoulos O, Proud D, Adkinson NF, Norman PS, Kagey-Sobotka A, Lichtenstein LM, Naclerio RM. Relationship between the early, late, and rechallenge reaction to nasal challenge with antigen: observations on the role of inflammatory mediators and cells. J Allergy Clin Immunol 1990; 86:851-61. PubMed
  • Charlesworth EN, Iliopoulos O, MacDonald SM, Kagey-Sobotka A, Lichtenstein LM. Cells and secretagogues involved in the human late-phase response. Int Arch Allergy Appl Immunol 1988; 88:50-3. PubMed
  • Iliopoulos O, Proud D, Norman PS, Lichtenstein LM, Kagey-Sobotka A, Naclerio RM. Nasal challenge with cold, dry air induces a late-phase reaction. Am Rev Respir Dis 1988; 138:400-5. PubMed
  • Togias A, Naclerio RM, Proud D, Pipkorn U, Bascom R, Iliopoulos O, Kagey-Sobotka A, Norman PS, Lichtenstein LM. Studies on the allergic and nonallergic nasal inflammation. J Allergy Clin Immunol 1988; 81:782-90. PubMed
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