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Vanderbilt-Ingram Cancer CenterVanderbilt-Ingram Cancer Center

 

VICC toll-free number 1-877-936-8422

Alexander Zaika, Ph.D.

Associate Professor of Cancer Biology
Associate Professor of Surgery (Surgical Oncology)
Assistant Professor of Cancer Biology
Researcher

Contact Information:

Vanderbilt University Medical Center
1255 Light Hall
Nashville , TN 37232-2733
615-322-7209
Fax: 615-343-1355

Research Description

p53 protein family, which consists of p53, p63 and p73, plays a pivotal role in regulation of multiple cellular mechanisms including apoptosis, cell cycle control and DNA damage repair. We are interested in understanding the molecular and cellular machinery that underlie the functions of these proteins. Although the role of p53 in human studies is relatively well studied, less is known about p73 and p63. Our analyses demonstrated that p73 and p63 family interact with each-other and these interactions play a critical role in human tumorigenesis. Our data also suggest that these proteins are strongly involved in a response to anticancer curative treatment. We are using a number of different in vitro and in vivo techniques to examine the role of the p53 protein family in cancer development and progression.


Publications
  • Wei J, Noto JM, Zaika E, Romero-Gallo J, Piazuelo MB, Schneider B, El-Rifai W, Correa P, Peek RM, Zaika AI. Bacterial CagA protein induces degradation of p53 protein in a p14ARF-dependent manner. Gut [print-electronic]. 2015 Jul; 64(7): 1040-8. PMID: 25080447, PMCID: PMC4312278, PII: gutjnl-2014-307295, DOI: 10.1136/gutjnl-2014-307295, ISSN: 1468-3288.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/25080447.
  • Zaika AI. Bacterial Pathogen Helicobacter pylori: A Bad AKTor Inhibits p53 Protein Activity [corrected] [editorial]. Dig. Dis. Sci. 2015 Apr; 60(4): 822-3. PMID: 25567053, PMCID: PMC4409465, DOI: 10.1007/s10620-014-3511-x, ISSN: 1573-2568.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/25567053.
  • Bhardwaj V, Noto JM, Wei J, Andl C, El-Rifai W, Peek RM, Zaika AI. Helicobacter pylori bacteria alter the p53 stress response via ERK-HDM2 pathway. Oncotarget. 2015 Jan 1/30/2015; 6(3): 1531-43. PMID: 25605238, PMCID: PMC4359312, PII: 2828, DOI: 10.18632/oncotarget.2828, ISSN: 1949-2553.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/25605238.
  • Zaika E, Bhardwaj V, Wei J, Washington MK, Souza R, El-Rifai W, Zaika A. Proinflammatory cytokines and bile acids upregulate ¿Np73 protein, an inhibitor of p53 and p73 tumor suppressors. PLoS ONE [electronic-print]. 2013; 8(5): e64306. PMID: 23717592, PMCID: PMC3661465, PII: PONE-D-13-03381, DOI: 10.1371/journal.pone.0064306, ISSN: 1932-6203.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/23717592.
  • Zaika A, Wei J, Noto J, Peek R. Regulation of the p53 tumor suppressor by gastric pathogen Helicobacter pylori pathogen. Oncotarget [print-electronic]. 2012 Oct 10/8/2012; PMID: 23060526, PII: 698, DOI: 10.18632/oncotarget.698, ISSN: 1949-2553.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/23060526.
  • Wei J, Noto J, Zaika E, Romero-Gallo J, Correa P, El-Rifai W, Peek RM, Zaika A. Pathogenic bacterium Helicobacter pylori alters the expression profile of p53 protein isoforms and p53 response to cellular stresses. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2012 Sep 9/18/2012; 109(38): E2543-50. PMID: 22927405, PMCID: PMC3458371, PII: 1205664109, DOI: 10.1073/pnas.1205664109, ISSN: 1091-6490.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/22927405.
  • Wei J, Zaika E, Zaika A. P53 Family: Role of Protein Isoforms in Human Cancer. J Nucleic Acids [print-electronic]. 2012; 2012: 687359. PMID: 22007292, PMCID: PMC3191818, DOI: 10.1155/2012/687359, ISSN: 2090-021X.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/22007292.
  • Zaika E, Wei J, Yin D, Andl C, Moll U, El-Rifai W, Zaika AI. P73 protein regulates DNA damage repair. FASEB J [print-electronic]. 2011 Dec; 25(12): 4406-14. PMID: 21891782, PMCID: PMC3236618, PII: fj.11-192815, DOI: 10.1096/fj.11-192815, ISSN: 1530-6860.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/21891782.
  • Vilgelm AE, Hong SM, Washington MK, Wei J, Chen H, El-Rifai W, Zaika A. Characterization of ¿Np73 expression and regulation in gastric and esophageal tumors. Oncogene [print-electronic]. 2010 Oct 10/28/2010; 29(43): 5861-8. PMID: 20676143, PMCID: PMC4152004, PII: onc2010319, DOI: 10.1038/onc.2010.319, ISSN: 1476-5594.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/20676143.
  • Wei J, Nagy TA, Vilgelm A, Zaika E, Ogden SR, Romero-Gallo J, Piazuelo MB, Correa P, Washington MK, El-Rifai W, Peek RM, Zaika A. Regulation of p53 tumor suppressor by Helicobacter pylori in gastric epithelial cells. Gastroenterology [print-electronic]. 2010 Oct; 139(4): 1333-43. PMID: 20547161, PMCID: PMC2949494, PII: S0016-5085(10)00877-2, DOI: 10.1053/j.gastro.2010.06.018, ISSN: 1528-0012.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/20547161.
  • Vilgelm AE, Washington MK, Wei J, Chen H, Prassolov VS, Zaika AI. Interactions of the p53 protein family in cellular stress response in gastrointestinal tumors. Mol. Cancer Ther [print-electronic]. 2010 Mar; 9(3): 693-705. PMID: 20197393, PMCID: PMC2838189, PII: 1535-7163.MCT-09-0912, DOI: 10.1158/1535-7163.MCT-09-0912, ISSN: 1538-8514.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/20197393.
  • Vilgelm A, El-Rifai W, Zaika A. Therapeutic prospects for p73 and p63: rising from the shadow of p53. Drug Resist. Updat [print-electronic]. 2008 Aug; 11(4-5): 152-63. PMID: 18801697, PMCID: PMC2585826, PII: S1368-7646(08)00046-0, DOI: 10.1016/j.drup.2008.08.001, ISSN: 1532-2084.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/18801697.
  • Wei J, O'Brien D, Vilgelm A, Piazuelo MB, Correa P, Washington MK, El-Rifai W, Peek RM, Zaika A. Interaction of Helicobacter pylori with gastric epithelial cells is mediated by the p53 protein family. Gastroenterology [print-electronic]. 2008 May; 134(5): 1412-23. PMID: 18343378, PMCID: PMC2430883, PII: S0016-5085(08)00178-9, DOI: 10.1053/j.gastro.2008.01.072, ISSN: 1528-0012.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/18343378.
  • Vilgelm A, Wei JX, Piazuelo MB, Washington MK, Prassolov V, El-Rifai W, Zaika A. DeltaNp73alpha regulates MDR1 expression by inhibiting p53 function. Oncogene [print-electronic]. 2008 Apr 4/3/2008; 27(15): 2170-6. PMID: 17952118, PMCID: PMC4066670, PII: 1210862, DOI: 10.1038/sj.onc.1210862, ISSN: 1476-5594.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/17952118.
  • Zaika AI, El-Rifai W. The role of p53 protein family in gastrointestinal malignancies. Cell Death Differ. 2006 Jun; 13(6): 935-40. PMID: 16557273, PII: 4401897, DOI: 10.1038/sj.cdd.4401897, ISSN: 1350-9047.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/16557273.
  • Tomkova K, Belkhiri A, El-Rifai W, Zaika AI. P73 isoforms can induce T-cell factor-dependent transcription in gastrointestinal cells. Cancer Res. 2004 Sep 9/15/2004; 64(18): 6390-3. PMID: 15374945, PII: 64/18/6390, DOI: 10.1158/0008-5472.CAN-04-2176, ISSN: 0008-5472.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/15374945.
  • Joseph TW, Zaika A, Moll UM. Nuclear and cytoplasmic degradation of endogenous p53 and HDM2 occurs during down-regulation of the p53 response after multiple types of DNA damage. FASEB J. 2003 Sep; 17(12): 1622-30. PMID: 12958168, PII: 17/12/1622, DOI: 10.1096/fj.02-0931com, ISSN: 1530-6860.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/12958168.
  • Petrenko O, Zaika A, Moll UM. DeltaNp73 facilitates cell immortalization and cooperates with oncogenic Ras in cellular transformation in vivo. Mol. Cell. Biol. 2003 Aug; 23(16): 5540-55. PMID: 12897129, PMCID: PMC166317, ISSN: 0270-7306.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/12897129.
  • Mihara M, Erster S, Zaika A, Petrenko O, Chittenden T, Pancoska P, Moll UM. P53 has a direct apoptogenic role at the mitochondria. Mol. Cell. 2003 Mar; 11(3): 577-90. PMID: 12667443, PII: S1097276503000509, ISSN: 1097-2765.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/12667443.
  • Zaika AI, Slade N, Erster SH, Sansome C, Joseph TW, Pearl M, Chalas E, Moll UM. DeltaNp73, a dominant-negative inhibitor of wild-type p53 and TAp73, is up-regulated in human tumors. J. Exp. Med. 2002 Sep 9/16/2002; 196(6): 765-80. PMID: 12235210, PMCID: PMC2194062, ISSN: 0022-1007.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/12235210.
  • Shirangi TR, Zaika A, Moll UM. Nuclear degradation of p53 occurs during down-regulation of the p53 response after DNA damage. FASEB J [print-electronic]. 2002 Mar; 16(3): 420-2. PMID: 11790725, PII: 01-0617fje, DOI: 10.1096/fj.01-0617fje, ISSN: 1530-6860.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/11790725.
  • Moll UM, Erster S, Zaika A. P53, p63 and p73--solos, alliances and feuds among family members. Biochim. Biophys. Acta. 2001 Dec 12/28/2001; 1552(2): 47-59. PMID: 11825686, PII: S0304419X01000361, ISSN: 0006-3002.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/11825686.
  • Zaika A, Irwin M, Sansome C, Moll UM. Oncogenes induce and activate endogenous p73 protein. J. Biol. Chem [print-electronic]. 2001 Apr 4/6/2001; 276(14): 11310-6. PMID: 11115495, PII: M005737200, DOI: 10.1074/jbc.M005737200, ISSN: 0021-9258.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/11115495.
  • Moll UM, Zaika A. Nuclear and mitochondrial apoptotic pathways of p53. FEBS Lett. 2001 Mar 3/30/2001; 493(2-3): 65-9. PMID: 11286997, PII: S0014-5793(01)02284-0, ISSN: 0014-5793.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/11286997.
  • Sansome C, Zaika A, Marchenko ND, Moll UM. Hypoxia death stimulus induces translocation of p53 protein to mitochondria. Detection by immunofluorescence on whole cells. FEBS Lett. 2001 Jan 1/19/2001; 488(3): 110-5. PMID: 11163756, PII: S0014-5793(00)02368-1, ISSN: 0014-5793.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/11163756.
  • Moll UM, Zaika A. Disrupting the p53-mdm2 interaction as a potential therapeutic modality. Drug Resist. Updat. 2000 Aug; 3(4): 217-21. PMID: 11498389, PII: S1368-7646(00)90160-2, DOI: 10.1054/drup.2000.0160, ISSN: 1532-2084.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/11498389.
  • Marchenko ND, Zaika A, Moll UM. Death signal-induced localization of p53 protein to mitochondria. A potential role in apoptotic signaling. J. Biol. Chem. 2000 May 5/26/2000; 275(21): 16202-12. PMID: 10821866, PII: 275/21/16202, ISSN: 0021-9258.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/10821866.
  • Kovalev S, Mateen A, Zaika AI, O'Hea BJ, Moll UM. Lack of defective expression of the ATM gene in sporadic breast cancer tissues and cell lines. Int. J. Oncol. 2000 Apr; 16(4): 825-31. PMID: 10717253, ISSN: 1019-6439.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/10717253.
  • Zaika AI, Kovalev S, Marchenko ND, Moll UM. Overexpression of the wild type p73 gene in breast cancer tissues and cell lines. Cancer Res. 1999 Jul 7/1/1999; 59(13): 3257-63. PMID: 10397274, ISSN: 0008-5472.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/10397274.
  • Zaika A, Mozzherin DJ, Tan CK, Downey KM, Fisher PA. A two-dimensional support for selective binding of polyhistidine-tagged proteins: identification of a proliferating cell nuclear antigen point mutant with altered function in vitro. Anal. Biochem. 1999 Mar 3/15/1999; 268(2): 193-200. PMID: 10075808, PII: S0003-2697(98)93074-3, DOI: 10.1006/abio.1998.3074, ISSN: 0003-2697.
    Available from: http://www.ncbi.nlm.nih.gov/pubmed/10075808.