Michael Shtutman, Ph.D.

Assistant Professor

803.777.8988 | CLS 713A

Dr.Shtutman's Email

Dr. Michael Shtutman

Research Interest

The general research direction of my laboratory is identifying and exploring new molecular targets for cancer therapy using the methods of functional genomics, in particular the selection of phenotype-modifying short hairpin RNAs (shRNAs) and genetic suppressor elements (GSEs). The principal novel target that we have identified is the Zeta subunit of the COPI complex that coats intracellular vesicles and is involved in intracellular traffic and autophagy.

Two alternative forms of the Zeta subunit are encoded by the genes COPZ1 and COPZ2, and we have discovered that many types of cancer no longer express COPZ2, making such tumors uniquely dependent on COPZ1. COPZ1 inhibition has little effect on normal cells but it kills tumor cells, both proliferating and quiescent, thus offering the potential for complete eradication of the tumor. We have found that COPZ2 silencing in cancers is a consequence of the inactivation of a tumor-suppressive micro RNA, miR152, which is encoded within the COPZ2 gene. Our current studies are concentrated on exploring COPZ1 as a novel target for cancer therapy and elucidating the mechanisms of the tumor-suppressive activity of miR152.

 

Education

Doctor of Philosophy, Experimental Oncology 1990-1996
Cancer Research Center, Moscow, Russia

Masters of Science, Biotechnology 1982-1988
Moscow Mendeleev Chemical - Technological Institute,
Department of Biotechnology, Moscow, Russia

Postdoctoral Fellow 1997-1999
Department of Molecular Cell Biology
Weizmann Institute of Science, Rehovot, Israel

Publications

  • Charles C. Weige, Marc R. Birtwistle,  Himel Mallick, Nengjun Yi, Zuzana Berrong, Emily Cloessner, Keely Duff, Josephine Tidwell, Megan Clendenning, Brent Wilkerson, Christopher Farrell, Fred Bunz, Hao Ji, Michael Shtutman,  Kim E. Creek, Carolyn E. Banister, Phillip J. Buckhaults. Transcriptomes and shRNA Suppressors in a TP53 Allele-specific Model of Early-onset Colon Cancer in African Americans., Molecular Cancer Research , 2014 Jul;12(7):1029-41 a
  • Shtutman M, Baig M, Levina E, Hurteau G, Lim CU, Broude E, Nikiforov M, Harkins TT, Carmack CS, Ding Y, Wieland F, Buttyan R, Roninson IB. Tumor-specific silencing of COPZ2 gene encoding coatomer protein complex subunit {zeta}2 renders tumor cells dependent on its paralogous gene COPZ1. Proc Natl Acad Sci U S A. 2011 Jul 26;108(30):12449-54
  • Shtutman, M., Maliyekkel, A., Shao, Y., Carmack, C.S., Baig, M., Warholic, N., Cole, K., Broude, E.V., Harkins, T.T., Ding, Y., and Roninson, I.B. (2010). Function-based gene identification using enzymatically generated normalized shRNA library and massive parallel sequencing. Proc. Natl. Acad. Sci. USA, 107, 7377-7382. 
  • Shtutman M, J. Zhurinsky, I.Simcha, C. Albanese, M. D’Amico, R. Pestell, A. Ben-Ze'ev.  The cyclin D1 gene is a target of the catenin/LEF-1 pathway. Proc Natl Acad Sci U S A. 1999 May 11;96(10):5522-5527
  • Levina E, Chen M, Carkner R, Shtutman M, Buttyan R. Paracrine Hedgehog increases the steroidogenic potential of prostate stromal cells in a Gli-dependent manner. Prostate. 2012 Jun 1;72(8):817-24.
  • Shtutman M, Roninson IB. A subunit of coatomer protein complex offers a novel tumor-specific target through a surprisingmechanism. Autophagy. 2011 Dec;7(12):1551-2
  • Chaturvedi S, Rajkumar SS, Li X, Hurteau GJ, Shtutman M, Chaturvedi V. Antifungal testing and high-throughput screening of compound library against Geomyces destructans, the etiologic agent of geomycosis (WNS) in bats. PLoS One. 2011 Mar 2;6(3):e17032
  • Tanner MJ, Welliver RC Jr, Chen M, Shtutman M, Godoy A, Smith G, Mian BM, Buttyan R. Effects of androgen receptor and androgen on gene expression in prostate stromal fibroblasts and paracrine signaling to prostate cancer cells. PLoS One. 2011 Jan 18;6(1):e16027
  • Chen M, Feuerstein MA, Levina E, Baghel PS, Carkner RD, Tanner MJ, Shtutman M, Vacherot F, Terry S, de la Taille A, Buttyan R. Hedgehog/Gli supports androgen signaling in androgen deprived and androgen independent prostate cancer cells. Mol Cancer. 2010 Apr 26;9:89
  • Demidenko ZN, Shtutman M, Blagosklonny MV Pharmacologic inhibition of MEK and PI-3K converges on the mTOR/S6 pathway to decelerate cellular senescence. Cell Cycle. 2009 Jun 15;8(12):1896-900
  • Shtutman M, Chausovsky A, Prager-Khoutorsky M, Schiefermeier N, Boguslavsky S, Kam Z, Fuchs E, Geiger B, Borisy GG, BershadskyAD. Stabilization of non-centrosomal microtubules by membrane-targeted a-catenin Cell Cycle, 2008, Aug;7(15):2377-83(Co-Corresponding author).
  • Shlomit Boguslavsky, Inna Grosheva, Elad Landau, Miriam Cohen, Katya Arnold, Michael Shtutman, Elena Feinstein, BenjaminGeiger, and Alexander Bershadsky; 120 catenin regulates lamellipodial dynamics and cell adhesion in cooperation with cortactin; PNAS, 2007, 104, 10882-7
  • Gavert N, Sheffer M, Raveh S, Spaderna S, Shtutman M, Brabletz T, Barany F, Paty P, Notterman D, Domany E, Ben-Ze’ev A;Expression of L1-CAM and ADAM10 in human colon cancer cells induces metastasis. Cancer Research, 2007 67, 7703-12.
  • Shtutman M, Levina E, Ohouo P, Biag M, Roninson I. Cell adhesion molecule L1 disrupts E-cadherin containing adherens junctions and increases scattering and motility of MCF7 breast carcinoma cells. Cancer Research, 2006, 66, 11370-80 (Co-Corresponding author).
  • Teuliere J, Faraldo MM, Deugnier MA, Shtutman M, Ben-Ze'ev A, Thiery JP, Glukhova MA. Targeted activation of b-catenin signaling in basal mammary epithelial cells affects mammary development and leads to hyperplasia. Development., 2005, 132, 267-77.
  • Teuliere J, Faraldo MM, Shtutman M, Birchmeier W, Huelsken J, Thiery JP, Glukhova MA. b-catenin-dependent and -independent effects of delta N-plakoglobin on epidermal growth and differentiation. Mol. Cell. Biol., 2004, 24, 8649-61.
  • Brodsky L, Leontovich A, Shtutman M, Feinstein E. Identification and handling of artifactual gene expression profiles emerging in microarray hybridization experiments. Nucleic Acids Res., 2004, 32, e46.
  • Shtutman M, Zhurinsky J, Oren M, Levina E, Ben-Ze'ev A. PML Is a target gene of b-catenin and plakoglobin, and coactivates b-catenin-mediated transcription. Cancer Res. 2002, 62, 5947-54.
  • Conacci-Sorrell ME, Ben-Yedidia T, Shtutman M, Feinstein E, Einat P, Ben-Ze'ev A. Nr-CAM is a target gene of the b-catenin/LEF-1 pathway in melanoma and colon cancer and its expression enhances motility and confers tumorigenesis. Genes Dev.2002, 16, 2058-72.
  • Damalas A, Kahan S, Shtutman M, Ben-Ze'ev A, Oren M. Deregulated b-catenin induces a p53- and ARF-dependent growth arrest and cooperates with Ras in transformation. EMBO J., 2001, 20, 4912-4922.
  • Simcha I, Kirkpatrick C, Sadot E, Shtutman M, Polevoy G, Geiger B, Peifer M, Ben-Ze'ev A. Cadherin sequences that inhibit b-catenin signaling: a study in yeast and mammalian cells. Mol. Biol. Cell., 2001, 12, 1177-1188.
  • Goichberg P, Shtutman M, Ben-Ze'ev A, Geiger B. Recruitment of b-catenin to cadherin-mediated intercellular adhesions isinvolved in myogenic induction. J. Cell Sci., 2001, 114, 1309-1319.
  • Grosheva I, Shtutman M, Elbaum M, Bershadsky AD. p120 catenin affects cell motility via modulation of activity of Rho-family GTPases: a link between cell-cell contact formation and regulation of cell locomotion, J Cell Sci., 2001, 114, 695-707.
  • Chepurnyh TV, Shtutman MS, Bykova AV, Ianushevich IG, Tatosian AG. Vesicular transport gene bet1 is differentially transcribed in transformed cells with various metastatic potential. Mol. Biol. (Mosk)., 2000, 34, 907-910 (in Russian).
  • Ben-Ze'ev A, Shtutman M, Zhurinsky J. The integration of cell adhesion with gene expression: the role of b-catenin. Exp. Cell Res., 2000, 261, 75-82. 
  • Zhurinsky J, Shtutman M, Ben-Ze'ev A. Plakoglobin and b-catenin: protein interactions, regulation and biological roles. J. Cell Sci., 2000, 113, 3127-39. 
  • Zhurinsky J, Shtutman M, Ben-Ze'ev A.  Differential mechanisms of LEF/TCF family-dependent transcriptional activation by b-catenin and plakoglobin. Mol. Cell. Biol., 2000, 20, 4238-52 (equal contribution with ZJ). 
  •  D'Amico M, Hulit J, Amanatullah DF, Zafonte BT, Albanese C, Bouzahzah B, Fu M, Augenlicht LH, Donehower LA, Takemaru K, Moon RT, Davis R, Lisanti MP, Shtutman M, Zhurinsky J, Ben-Ze'ev A, Troussard AA, Dedhar S, Pestell RG. The integrin-linked kinase regulates the cyclin D1 gene through glycogen synthase kinase 3b and cAMP-responsive element-binding protein-dependent pathways. J. Biol Chem., 2000, 275, 32649-57. 
  • Hulit J, Bash T, Fu M, Galbiati F, Albanese C, Sage DR, Schlegel A, Zhurinsky J, Shtutman M, Ben-Ze'ev A, Lisanti MP, Pestell RG. The cyclin D1 gene is transcriptionally repressed by caveolin-1. J. Biol. Chem., 2000, 275, 21203-9. 
  •  Helfman D, E. Levy, C. Berthier, M. Shtutman, M. Elbaum, A. Bershadsky.Caldesmon inhibits cell contractility and interferes with Rho-dependent formation of focal adhesions. Mol. Biol. Cell., 1999, 10, 3097-3112 (equal contribution wit EL and CB). 
  •  Damalas A, A Ben-Ze'ev, I Simcha, M Shtutman, JF Leal, J Zhurinsky, B Geiger, M Oren. Excess b-catenin promotes accumulation of transcriptionally active p53. EMBO J., 1999, 18, 3054-3063. 
  • Elbaum M, A. Chausovsky, E. Levy, M. Shtutman and A.D. Bershadsky.  Microtubule involvement in regulating cell contractility and adhesion-dependent signaling: a possible mechanism for polarization of cell motility. Biochem. Soc. Symp., 1999, 65, 147-172 
  • Sadot E, I. Simcha, M. Shtutman, A. Ben-Ze'ev, B. Geiger.  Inhibition of b-catenin transactivation by cadherin derivatives. Proc. Natl. Acad. Sci. USA., 1998, 95, 15339-15344. 
  • Simcha I, M. Shtutman, D. Salomon, J. Zhurinsky, E. Sadot, B. Geiger, A. Ben-Ze'ev. Differential nuclear localization and transactivation potential of b-catenin and plakoglobin., J. Cell Biol., 1998, 141, 1433-1448. 
  • Zborovskaya I, Gasparian A, Kitaeva M, Polotzky  B, Tupitzin N, Machaladze Z, Gerasimov S, Shtutman M, Jakubovskaya M, Davidov M, Tatosyan A.  Simultaneous detection of genetic and immunological markers in non-small cell lung cancer: prediction of metastatic potential of tumor. Clinical & Experimental Metastasis, 1996, 14, 490-500. 
  •  Tatosyan  A.G, Yatsulo B, Shtutman M, Moinova E, Kaverina I, Musarkina E, Leskov K, Mizenina O, Calothy G, Dezelee P. Two novel variants of v-src oncogene isolated from low and high metastatic RSV-transformed hamster cells. Virology, 1996, 216, 347-356. 
  •  Stepina V. Seniuta N., Bakieva N, Pavlish O., Syrtsev A., Budnikova L, Susova O, Shtutman M, Shcherbak L., Gurtsevich V. Serological and molecular-biological study of T-cell leukemia virus in Turkmenistan. Voprosi Virusol., 1996, 41, 174-178 (in Russian). 
  •  Gurskaya N, Shagin D,. Lukyanov K,. Vagner L, Shtutman M, Musarkina E, Moinova E, Tatosyan  A, Lukyanov S,. Sverdlov E. Cloning of the hm-SDRGF cDNA from sirian  hamster cell line with high metastatic  potential by subtractive hybridization of cDNA Bioorgan. Chim, 1996, 22, 425-431 (in Russian). 
  •  Tchevkina E., Kisseljova N., Shtutman M, Musatkina E., Mizenina O., Leskov K, Tavitian A., Kisseljov F. Suppression and restoration of v-src expression in RSV transformed cells after transfection with N-ras and its antagonist. Int. J. Oncology, 1995, 7, 453-459. 
  • Krasilnikov M, Shatskaya V, Shtutman M. Regulation of phospholipid turnover in hamster fibroblasts, transformed by oncogenes v-src and N-ras. Biochemistry (Moscow), 1995, 59, 1315-1320 (in Russian). 
  • Komissarova E, Pantin V, Pavlova L., Boronkova T, Soyfer M, Shtutman M, Zaritova F, Grinjova N, Kisseljov F. Transformation of rat fibroblasts  with E6 and E7 genes of HPV 18 and their stable reversion by E7 antisence oligonucleotide. Proceedings of Russian Academy of Science, 1994, 338, 404-407 (in Russian). 
  • Topol L., Kisseljova N., Gutierres L., Deichman G., Musatkina E., Shtutman M., Zakamaldina T., Blair D., Tatosyan A. Modulation of pp60v-src and pp60c-src expression in RSV transformed hamster fibroblast transfected with activated N-ras. Molecular Carcinogenesis, 1993, 8, 167-176. 
  • Rezikyan S, Voevodin A, Klots I, Shtutman M., Lapin B. Isolation and characterisation of African green monkey’s lentivirus related HIV. Voprosy Virusologii, 1993, 2, 54-56 (in Russian). 
  • Tatosyan A., Shtutman M., Topol L., Kisseljova N., Musatkina E., Deichman G. Selective integration of virus genome in high and low metastatic transformed cell lines. Modern Trends in Human Leukemia, 1992, 9, 260-261.