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Huebner, F. Kay PhD

Professor

Department of Molecular Virology, Immunology and Medical Genetics Human Cancer Genetics Program

Contact information:

Office:

916 Biomedical Research Tower
460 W 12th Avenue
Columbus, OH 43210
Ph. (614) 292-4850
laboratory phone: 614-292-3716
fax 614-292-3312
email address: kay.huebner@osumc.edu 

Research interest:

Cancer, DNA Damage, Carcinoma, Breast Cancer, Carcinoma, Renal Cell, Loss of Heterozygosity, Leukemia, Lung Cancer

 The major focus of the laboratory is to thoroughly investigate and define the biological functions of the tumor suppressor proteins, Fhit and Wwox, encoded by the chromosome fragile sites FRA3B and FRA16D, two of the most frequently inactivated tumor suppressors in a broad spectrum of human cancers. The biological functions of the two proteins are studied using the full panoply of molecular genetic techniques in in vitro and in vivo models. Tumor suppressor related changes defined in tissue culture or mouse models are quickly examined also in human tissues from anonymous human cancers in order to confirm the laboratory findings in actual human cancers of breast, pancreas and other cancers, with the ultimate goal of identifying  prognostically useful protein markers and possible therapeutic targets for specific cancers.

Research summary:

The Laboratory is focused on understanding the role of fragile genes, that is, genes at common chromosomal fragile sites, in cancer development. The research currently entails studies of function of several genes, including FHIT and WWOX, definition of the signal pathways engaged by these genes in normal and cancer cells, and the consequences to cells, organs and organisms deficient for these genes, using the gamut of molecular genetic methods: normal and cancer cells, as well as mice deficient for genes of interest are used in comparative studies to define differences in negative and positive cells or animals; expression of the fragile genes or their effector genes are up or down modulated by transfection, and effect on biological or biochemical features assessed; interacting proteins are identified to build pathways; precancer and cancer phenotypes of knockout mice are assessed and viruses carrying the fragile suppressor genes are used in cancer prevention and therapy by infection of knockout mice to restore tumor suppressor expression; cells positive and negative for the genes of interest are compared using massive parallel analysis methods such as microarray expression profiling. The long-term goals are to: a) understand fragile tumor suppressor signal pathways and how their loss activates signal pathways that contribute to preneoplasia and neoplasia development, and b) identify targets for prevention and therapy within the activated signal pathways.

Education & Training:

PhD, Microbiology, University of Pennsylvania, 1974
Postdoctoral Training, Molecular Genetics, The Wistar Institute Cancer Center, Philadelphia, PA

Selected Publications:

Alder H, Taccioli C, Chen H, Jiang Y, Smalley KJ, Fadda P, Ozer HG, Huebner K, Farber JL, Croce CM, Fong LY. Dysregulation of miR-31 and miR-21 induced by zinc deficiency promotes esophageal cancer. Carcinogenesis. 2012 Sep;33(9):1736-44. Epub 2012 Jun 10.

Guler G, Balci S, Costinean S, Ussakli CH, Irkkan C, Suren D, Sari E, Altundag K, Ozisik Y, Jones S, Bacher J, Shapiro CL, Huebner K. Stem cell-related markers in primary breast cancers and associated metastatic lesions. Mod Pathol. 2012 Jul;25(7):949-55. doi: 10.1038/modpathol.2012.37. Epub 2012 Mar 2.

Volinia S, Galasso M, Sana ME, Wise TF, Palatini J, Huebner K, Croce CM. Breast cancer signatures for invasiveness and prognosis defined by deep sequencing of microRNA. Proc Natl Acad Sci U S A. 2012 Feb 21;109(8):3024-9. Epub 2012 Feb 6.

Shibata H, Miuma S, Saldivar JC, Huebner K. Response of subtype-specific human breast cancer-derived cells to poly(ADP-ribose) polymerase and checkpoint kinase 1 inhibition. Cancer Sci. 2011 Oct;102(10):1882-8. Epub 2011 Jul 21.

Drusco A, Pekarsky Y, Costinean S, Antenucci A, Conti L, Volinia S, Aqeilan RI, Huebner K, Zanesi N. Common fragile site tumor suppressor genes and corresponding mouse models of cancer. J Biomed Biotechnol. 2011;2011:984505. Epub 2010 Dec 29. Review.

Huebner K. Molecular biology: DNA fragility put into context. Nature. 2011 Feb 3;470(7332):46-7.

Fong LY, Jiang Y, Rawahneh ML, Smalley KJ, Croce CM, Farber JL, Huebner K. Zinc supplementation suppresses 4-nitroquinoline 1-oxide-induced rat oral carcinogenesis. Carcinogenesis. 2011 Apr;32(4):554-60. Epub 2011 Jan 18.

Sun J, Liu J, Pan X, Quimby D, Zanesi N, Druck T, Pfeifer GP, Croce CM, Fong LY, Huebner K. Effect of zinc supplementation on N-nitrosomethylbenzylamine-induced forestomach tumor development and progression in tumor suppressor-deficient mouse strains. Carcinogenesis. 2011 Mar;32(3):351-8. Epub 2010 Nov 19.

Guler G, Himmetoglu C, Jimenez RE, Geyer SM, Wang WP, Costinean S, Pilarski RT, Morrison C, Suren D, Liu J, Chen J, Kamal J, Shapiro CL, Huebner K. Aberrant expression of DNA damage response proteins is associated with breast cancer subtype and clinical features. Breast Cancer Res Treat. 2011 Sep;129(2):421-32. doi: 10.1007/s10549-010-1248-6. Epub 2010 Nov 11.

Volinia S, Galasso M, Costinean S, Tagliavini L, Gamberoni G, Drusco A, Marchesini J, Mascellani N, Sana ME, Abu Jarour R, Desponts C, Teitell M, Baffa R, Aqeilan R, Iorio MV, Taccioli C, Garzon R, Di Leva G, Fabbri M, Catozzi M, Previati M, Ambs S, Palumbo T, Garofalo M, Veronese A, Bottoni A, Gasparini P, Harris CC, Visone R, Pekarsky Y, de la Chapelle A, Bloomston M, Dillhoff M, Rassenti LZ, Kipps TJ, Huebner K, Pichiorri F, Lenze D, Cairo S, Buendia MA, Pineau P, Dejean A, Zanesi N, Rossi S, Calin GA, Liu CG, Palatini J, Negrini M, Vecchione A, Rosenberg A, Croce CM. Reprogramming of miRNA networks in cancer and leukemia. Genome Res. 2010 May;20(5):589-99.

Salah Z, Aqeilan R, Huebner K. WWOX gene and gene product: tumor suppression through specific protein interactions. Future Oncol. 2010 Feb;6(2):249-59. Review.

Cirombella R, Montrone G, Stoppacciaro A, Giglio S, Volinia S, Graziano P, Huebner K, Vecchione A. Fhit loss in lung preneoplasia: relation to DNA damage response checkpoint activation. Cancer Lett. 2010 May 28;291(2):230-6.

Rimessi A, Marchi S, Fotino C, Romagnoli A, Huebner K, Croce CM, Pinton P, Rizzuto R. Intramitochondrial calcium regulation by the FHIT gene product sensitizes to apoptosis. Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):12753-8. Epub 2009 Jul 21.

Guler G*, Huebner K*, Himmetoglu C, Jimenez R, Costinean S, Volinia S, Pilarski RT, Hayran M, Shapiro? CL Fhit, Wwox and AP2γ expression levels correlate with basal phenotype in breast cancer. Cancer, in press, Jan. 5, 2009 (equal contributors).

Pichiorri F, Okumura H, Nakamura T, Garrison PN, Gasparini P, Suh SS, Druck T, McCorkell KA, Barnes LD, Croce CM, Huebner K. Correlation of fragile histidine triad (Fhit) protein structural features with effector interactions and biological functions. J Biol Chem. 2008 Nov 12. [Epub ahead of print]

Trapasso F, Pichiorri F, Gaspari M, Palumbo T, Aqeilan RI, Gaudio E, Okumura H, Iuliano R, Di Leva G, Fabbri M, Birk DE, Raso C, Green-Church K, Spagnoli LG, Venuta S, Huebner K, Croce CM. Fhit interaction with ferredoxin reductase triggers generation of reactive oxygen species and apoptosis of cancer cells. J Biol Chem. 2008 May 16;283(20):13736-44.

Pichiorri F, Ishii H, Okumura H, Trapasso F, Wang Y, Huebner K. Molecular parameters of genome instability: roles of fragile genes at common fragile sites. J Cell Biochem. 2008 Aug 1;104(5):1525-33. Review.

Nakayama S, Semba S, Maeda N, Aqeilan RI, Huebner K, Yokozaki H. Role of the WWOX gene, encompassing fragile region FRA16D, in suppression of pancreatic carcinoma cells. Cancer Sci. 2008 Jul;99(7):1370-6.

Ishii H, Mimori K, Ishikawa K, Okumura H, Pichiorri F, Druck T, Inoue H, Vecchione A, Saito T, Mori M, Huebner K. Fhit-deficient hematopoietic stem cells survive hydroquinone exposure carrying precancerous changes. Cancer Res. 2008 May 15;68(10):3662-70.

 A full list of my publications can be found at: http://www.ncbi.nlm.nih.gov/sites/myncbi/kay.huebner.1/bibliography/40869720/public/?sort=date&direction=ascending