Memorial Hospital Research Laboratories // Ingo K. Mellinghoff

Ingo K. Mellinghoff: Selected Publications

Research Articles

Graham NA, Tahmasian M, Kohli B, Komisopoulou E, Zhu M, Vivanco I, Teitell MA, Wu H, Ribas A, Lo RS, Mellinghoff IK, Mischel PS, Graeber TG. Glucose deprivation activates a metabolic and signaling amplification loop leading to cell death. Mol Syst Biol. 2012 Jun 26;8:589. doi: 10.1038/msb.2012.20.

Vivanco I, Robins HI, Rohle D, Campos C, Grommes C, Nghiemphu PL, Kubek S, Oldrini B, Chheda MG, Yannuzzi N, Tao H, Zhu S, Iwanami A, Kuga D, Dang J, Pedraza A, Brennan CW, Heguy A, Liau LM, Lieberman F, Yung WK, Gilbert MR, Reardon DA, Drappatz J, Wen PY, Lamborn KR, Chang SM, Prados MD, Fine HA, Horvath S, Wu N, Lassman AB, Deangelis LM, Yong WH, Kuhn JG, Mischel PS, Mehta MP, Cloughesy TF, Mellinghoff IK. Differential Sensitivity of Glioma- versus Lung Cancer-Specific EGFR Mutations to EGFR Kinase Inhibitors. Cancer Discov. 2012 May;2(5):458-471. Epub 2012 Mar 31.

Turcan S, Rohle D, Goenka A, Walsh LA, Fang F, Yilmaz E, Campos C, Fabius AW, Lu C, Ward PS, Thompson CB, Kaufman A, Guryanova O, Levine R, Heguy A, Viale A, Morris LG, Huse JT, Mellinghoff IK, Chan TA. IDH1 mutation is sufficient to establish the glioma hypermethylator phenotype. Nature. 2012 Feb 15;483(7390):479-83.

Lu C, Ward PS, Kapoor GS, Rohle D, Turcan S, Abdel-Wahab O, Edwards CR, Khanin R, Figueroa ME, Melnick A, Wellen KE, O'Rourke DM, Berger SL, Chan TA, Levine RL, Mellinghoff IK, Thompson CB. IDH mutation impairs histone demethylation and results in a block to cell differentiation. Nature. 2012 Feb 15;483(7390):474-8.

Palaskas N, Larson SM, Schultz N, Komisopoulou E, Wong J, Rohle D, Campos C, Yannuzzi N, Osborne JR, Linkov I, Kastenhuber ER, Taschereau R, Plaisier SB, Tran C, Heguy A, Wu H, Sander C, Phelps ME, Brennan C, Port E, Huse JT, Graeber TG, Mellinghoff IK. 18F-Fluorodeoxy-glucose Positron Emission Tomography Marks MYC-Overexpressing Human Basal-Like Breast Cancers. Cancer Res. 2011 Aug 1;71(15):5164-5174. Epub 2011 Jun 6.

Attolini CS, Cheng YK, Beroukhim R, Getz G, Abdel-Wahab O, Levine RL, Mellinghoff IK, Michor F. A mathematical framework to determine the temporal sequence of somatic genetic events in cancer. Proc Natl Acad Sci U S A. 2010 Sep 23. [Epub ahead of print]

Vivanco I, Rohle D, Versele M, Iwanami A, Kuga D, Oldrini B, Tanaka K, Dang J, Kubek S, Palaskas N, Hsueh T, Evans M, Mulholland D, Wolle D, Rajasekaran S, Rajasekaran A, Liau LM, Cloughesy TF, Dikic I, Brennan C, Wu H, Mischel PS, Perera T, Mellinghoff IK. The phosphatase and tensin homolog regulates epidermal growth factor receptor (EGFR) inhibitor response by targeting EGFR for degradation. Proc Natl Acad Sci U S A. 2010 Apr 6;107(14):6459-64. Epub 2010 Mar 22.

Guo D, Prins RM, Dang J, Kuga D, Iwanami A, Soto H, Lin KY, Huang TT, Akhavan D, Hock MB, Zhu S, Kofman AA, Bensinger SJ, Yong WH, Vinters HV, Horvath S, Watson AD, Kuhn JG, Robins HI, Mehta MP, Wen PY, Deangelis LM, Prados MD, Mellinghoff IK, Cloughesy TF, Mischel PS. EGFR Signaling Through an Akt-SREBP-1-Dependent, Rapamycin-Resistant Pathway Sensitizes Glioblastomas to Antilipogenic Therapy. Sci Signal.;2(101):ra82.

Veeriah S, Taylor BS, Meng S, Fang F, Yilmaz E, Vivanco I, Janakiraman M, Schultz N, Hanrahan AJ, Pao W, Ladanyi M, Sander C, Heguy A, Holland EC, Paty PB, Mischel PS, Liau L, Cloughesy TF, Mellinghoff IK, Solit DB, Chan TA. Somatic mutations of the Parkinson's disease-associated gene PARK2 in glioblastoma and other human malignancies. Nat Genet. 2009 Nov 29. [Epub ahead of print]

Gregorian C, Nakashima J, Dry SM, Nghiemphu PL, Smith KB, Ao Y, Dang J, Lawson G, Mellinghoff IK, Mischel PS, Phelps M, Parada LF, Liu X, Sofroniew MV, Eilber FC, Wu H. (2009) PTEN dosage is essential for neurofibroma development and malignant transformation. Proc Natl Acad Sci U S A. 2009 Oct 21. [Epub ahead of print]

Regales L, Gong Y, Shen R, de Stanchina E, Vivanco I, Goel A, Koutcher JA, Spassova M, Ouerfelli O, Mellinghoff IK, Zakowski MF, Politi KA, Pao W. Dual targeting of EGFR can overcome a major drug resistance mutation in mouse models of EGFR mutant lung cancer. J Clin Invest. 2009 Sep 14. pii: 38746. doi: 10.1172/JCI38746. [Epub ahead of print]

McGillicuddy LT, Fromm JA, Hollstein PE, Kubek S, Beroukhim R, De Raedt T, Johnson BW, Williams SM, Nghiemphu P, Liau LM, Cloughesy TF, Mischel PS, Parret A, Seiler J, Moldenhauer G, Scheffzek K, Stemmer-Rachamimov AO, Sawyers CL, Brennan C, Messiaen L, Mellinghoff IK, Cichowski K. Proteasomal and genetic inactivation of the NF1 tumor suppressor in gliomagenesis. Cancer Cell. 2009 Jul 7;16(1):44-54.

Veeriah S, Brennan C, Meng S, Singh B, Fagin JA, Solit DB, Paty PB, Rohle D, Vivanco I, Chmielecki J, Pao W, Ladanyi M, Gerald WL, Liau L, Cloughesy TC, Mischel PS, Sander C, Taylor B, Schultz N, Major J, Heguy A, Fang F, Mellinghoff IK, Chan TA. The tyrosine phosphatase PTPRD is a tumor suppressor that is frequently inactivated and mutated in glioblastoma and other human cancers. Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9435-40. Epub 2009 May 28

Du J, Bernasconi P, Clauser KR, Mani DR, Finn SP, Beroukhim R, Burns M, Julian B, Peng XP, Hieronymus H, Maglathlin RL, Lewis TA, Liau LM, Nghiemphu P, Mellinghoff IK, Louis DN, Loda M, Carr SA, Kung AL, Golub TR. Bead-based profiling of tyrosine kinase phosphorylation identifies SRC as a potential target for glioblastoma therapy. Nat Biotechnol. 2009 Jan;27(1):77-83. Epub 2008 Dec 21.

Yoshimoto K., Dang J., Zhu S, Nathanson D., Huang T., Dumont R., Seligson D.B., Yong W.H., Xiong Z., Rao N., Winther H., Chakravarti A., Bigner D.D., Mellinghoff I.K., Horvath S., Cavenee W.K., Cloughesy T.F., Mischel P.S. Development of a Real-time RT-PCR Assay for Detecting EGFRvIII in Glioblastoma Samples. Clin Cancer Res. 2008 Jan 15;14(2):488-493.

Cloughesy TF, Yoshimoto K, Nghiemphu P, Brown K, Dang J, Zhu S, Hsueh T, Chen Y, Wang W, Youngkin D, Liau L, Martin N, Becker D, Bergsneider M, Lai A, Green R, Oglesby T, Koleto M, Trent J, Horvath S, Mischel PS, Mellinghoff IK, Sawyers CL. Antitumor Activity of Rapamycin in a Phase I Trial for Patients with Recurrent PTEN-Deficient Glioblastoma. PLoS Med. 2008 Jan 22;5(1):e8.

Beroukhim R, Getz G, Nghiemphu L, Barretina J, Hsueh T, Linhart D, Vivanco I, Lee JC, Huang JH, Alexander S, Du J, Kau T, Thomas RK, Shah K, Soto H, Perner S, Prensner J, Debiasi RM, Demichelis F, Hatton C, Rubin MA, Garraway LA, Nelson SF, Liau L, Mischel PS, Cloughesy TF, Meyerson M, Golub TA, Lander ES, Mellinghoff IK, Sellers WR. Assessing the significance of chromosomal aberrations in cancer: methodology and application to glioma. Proc Natl Acad Sci USA. 2007 Dec 11;104(50):20007-12. Epub 2007 Dec 6.

Thomas R.K., Baker A.C., DeBiasi R., Winckler W., LaFramboise T., Lin W., Wang M., Feng W., Zander T., MacConnaill L., Lee J.C., Nicoletti R., Hatton C., Goyette M., Girard L., Majmudar K., Ziaugra L., Wong K.K., Gabriel S., Beroukhim R., Peyton M., Barretina J., Dutt A., Emery C., Greulich H., Shah K., Sasaki H., Gazdar A.F., Minna J., Armstrong S., Mellinghoff I.K., Hodi F., Dranoff G., Mischel P., Cloughesy T., Nelson S., Liau L., Mertz K., Rubin M., Moch H., Loda M., Catalona W., Fletcher J., Signoretti S., Kaye F., Anderson K.C., Demetri G., Dummer R., Wagner S., Herlyn M., Sellers W.R., Meyerson M., Garraway L.A. (2007). High-throughput oncogene mutation profiling in human cancer. Nature Genetics. 39 (3): 1-5.

Carlson M.R., Pope W.B., Horvath S., Braunstein J.G., Nghiemphu P., Tso C.L., Mellinghoff I.K., Lai A., Liau L.M., Mischel P.S., Dong J., Nelson S.F., Cloughesy T.F. (2007). Relationship between Survival and Edema in Malignant Gliomas: role of Vascular Endothelial Growth Factor and Neuronal Pentraxin 2. Clin Cancer Res. 13 (9): 2592-2598.

Vivanco I., Palaskas N., Tran C, Finn SP, Getz G, Kennedy NJ, Jiao J, Rose J, Xie W, Loda M, Golub T, Mellinghoff I.K., Davis RJ, Wu H, Sawyers CL. (2007). Identification of the JNK Signaling Pathway as a Functional Target of the Tumor Suppressor PTEN. Cancer Cell. 11: 555-569.

Thomas G.V., Tran C., Mellinghoff I.K., Welsbie D.S., Chan E., Fueger B., Czernin J., Sawyers C.L. (2006). Hypoxia-inducible factor determines sensitivity to mTOR inhibitors in kidney cancer. Nature Medicine. 1, 122-127.

Xin L, Teitell M.A, Lawson D.A., Kwon A., Mellinghoff I.K., and Witte O.N. (2006). Progression of prostate cancer by synergy of Akt with genotropic and nongenotropic actions of the androgen receptor. Proc Natl Acad Sci U S A 103, 7789-7794.

Beroukhim R., Lin M., Park Y., Hao K., Zhao X., Garraway L.A., Fox E.A., Hochberg E.P., Mellinghoff I.K., Hofer M.D., Descazeaud A., Rubin M.A., Meyerson M., Wong W.H., Sellers W.R., and Li C. (2006). Inferring loss-of-heterozygosity from unpaired tumors using high-density SNP-Arrays. PLoS Comput Biol 2(5); e41.

Wang M.Y., Lu K.V., Zhu S., Dia E.Q., Vivanco I., Shackleford G.M., Cavenee W., Mellinghoff I.K., Cloughesy T., Sawyers C.L., and Mischel P.S. (2006). Mammalian Target of Rapamycin Inhibition Promotes Response to Epidermal Growth Factor Receptor Kinase Inhibitors in PTEN-deficient and PTEN-intact glioblastoma cells. Cancer Res 66(16): 7864-7869.

Lee J.C., Vivanco I., Beroukhim R., Huang J.H.Y., Feng W.L., DeBiasi R.M., Yoshimoto K., King J.C., Nghiemphu P., Yuza Y., Xu Q., Greulich H., Thomas R., Paez G., Peck T., Linhart D.J., Glatt K.A., Getz G., Onofrio R., Ziaugra L., Levine R.L., Gabriel S., Kawaguchi T., O'Neill K., Khan H., Liau L.M., Nelson S., Rao P.N., Mischel P., Pieper R., Cloughesy T., Leahy D.J., Sellers W.R., Sawyers C.L., Meyerson M., and Mellinghoff I.K. (2006). EGFR activation in glioblastoma through novel missense mutations in the extracellular domain. PLoS Medicine. 12 (3): e485.

Waldherr, C., Mellinghoff, I.K., Tran, C., Halpern, B., Rozengurt, N., Safaei, A., Weber, W.A. , Stout, D., Satyamurthy, N., Barrio, J., Phelps, M.E., Silverman, D.H., Sawyers, C.L., and Czernin, J. (2005). Monitoring antiproliferative responses to kinase inhibitor therapy in mice with 3'-deoxy 3'-18Ffluorothymidine PET. J Nucl Med 46, 114-120.

Mellinghoff, I.K., Wang, M., Vivanco, I., Haas-Kogan, D., Zhu, S., Dia, E., Lu, K., Yoshimoto, K., Huang, J., Chute, D., Riggs, B.., Horvath, S., Liau, L., Cavenee, W., Rao, P., Beroukhim, R., Peck, T., Lee, J., Sellers, W., Stokoe, D., Prados, M., Cloughesy, T.F., Sawyers, C.L., Mischel, P.S. (2005). Molecular determinants of EGFR kinase inhibitor response in glioblastoma. The New England Journal of Medicine. 353, 2012-2024.

Gera, J.F., Mellinghoff, I.K., Shi, Y., Rettig, M.B., Tran, C., Hsu, J.H., Sawyers, C.L., and Lichtenstein, A.K. (2004). AKT activity determines sensitivity to mammalian target of rapamycin (mTOR) inhibitors by regulating cyclin D1 and c-myc expression. J Biol Chem 279, 2737-2746.

Mellinghoff, I.K., Vivanco, I., Kwon, A., Tran, C., Wongvipat, J., and Sawyers, C.L. (2004). HER2/neu kinase-dependent modulation of androgen receptor function through effects on DNA binding and stability. Cancer Cell 6, 517-527.

Mellinghoff I.K., Winston D.J., Mukwaya G., and Schiller G.J. (2002) Scedosporium apiospermum brain abscesses treated with posaconazole. Clinical Infectious Diseases, 34, 1648-1650.

Mellinghoff, I.K., Tran, C., and Sawyers, C.L. (2002). Growth inhibitory effects of the dual ErbB1/ErbB2 tyrosine kinase inhibitor PKI-166 on human prostate cancer xenografts. Cancer Res 62, 5254-5259.

Neshat MS, Mellinghoff, I.K., Tran, C., Stiles, B., Thomas, G., Petersen, R., Frost, P., Gibbons, J.J., Wu, H., and Sawyers, C.L. (2001). Enhanced sensitivity of PTEN deficient tumors to inhibition of FRAP/mTOR. Proc Natl Acad Sci U S A 98, 10314-10319.

Marder V.J. and Mellinghoff I.K. Cocaine and Buerger Disease (2000). Is there a pathogenetic association? Archives of Internal Medicine, 160, 2057-2060.

Mellinghoff I., Daibata M., Humphreys R.E., Mulder C., Takada K., and Sairenji T. (1991). Early events in Epstein-Barr virus genome expression after activation: regulation by second messengers of B cell activation. Virology, 185, 922-928.

Daibata D., Mellinghoff I., Takagi S., Humphreys R.E., and Sairenji T. (1991). Effect of Genistein, a tyrosine kinase inhibitor, on latent EBV activation by cross-linkage of membrane IgG in Akata B cells. Journal of Immunology, 147, 292-297.

Invited Reviews, Editorials, and Book Chapters

Deangelis LM, Mellinghoff IK. Virchow 2011 or How to ID(H) Human Glioblastoma. J Clin Oncol. 2011 Oct 24. (Epub ahead of print)

Mellinghoff IK, Schultz N, Mischel PS, Cloughesy TF. Will Kinase Inhibitors Make it as Glioblastoma Drugs? Curr Top Microbiol Immunol. 2011 Oct 21. (Epub ahead of print)

Mellinghoff IK, Lassman AB, Wen PY. Signal transduction inhibitors and antiangiogenic therapies for malignant glioma. Glia. 2011 Feb 23. doi: 10.1002/glia.21137. [Epub ahead of print]

Tracing cancer networks with phosphoproteomics. Solit DB, Mellinghoff IK. Nat Biotechnol. 2010 Oct;28(10):1028-29.

Vivanco I, Mellinghoff IK. Epidermal growth factor receptor inhibitors in oncology. Curr Opin Oncol. 2010 Aug 25. [Epub ahead of print]

Mellinghoff, I.K, Cloughesy T.F., Mischel, P.M. (2007). Molecular Pathways: PTEN-mediated resistance to EGFR kinase inhibitors. Clinical Cancer Research, 15: 378-81.

Mellinghoff I.K. (2007) Why Do Cancer Cells Become “Addicted” to Oncogenic Epidermal Growth Factor Receptor? PLoS Medicine, 4 (10), e321.

Mellinghoff, I.K. (2006) Novel Approaches to Androgen Receptor Blockade. In: Prostate Cancer: Translational and Emerging Therapies. N. A. Dawson and W. K. Kelly (editors), Taylor and Francis Publishing Group.

Mellinghoff, I.K., and Sawyers, C.L. (2004). TORward AKTually useful mouse models. Nature Medicine 10, 579-580.

Mellinghoff I.K., Sawyers C.L. (2002). The emergence of resistance to targeted cancer therapeutics. Pharmacogenomics, 3(5):603-623.

Mellinghoff, I. and Sawyers, C.L. (2000) Kinase Inhibitor Therapy in Cancer. PPO Updates, Principles & Practice of Oncology, Vincent T. Devita, Jr., Samuel Hellman, Steven A. Rosenberg (Eds). 5th Edition. Lippincott Williams & Wilkins 14(12):1-11.

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