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Last Name

Zdenka Matijasevic PhD

TitleAssistant Professor
InstitutionUniversity of Massachusetts Medical School
AddressUniversity of Massachusetts Medical School
55 Lake Avenue North
Worcester MA 01655
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    Other Positions
    InstitutionUMMS - School of Medicine

    InstitutionUMMS - Graduate School of Biomedical Sciences
    DepartmentBiochemistry and Molecular Pharmacology

    Collapse Biography 
    Collapse education and training
    University of Zagreb, Zagreb, , CroatiaBSBiotechnology
    University of Zagreb, Zagreb, , CroatiaMSMicrobial Genetics
    University of Zagreb, Zagreb, , CroatiaPHDEnvironmental Mutagenesis

    Collapse Overview 
    Collapse overview

    Cell and Developmental Biology

    Academic Background

    BS, 1971; MSc, 1976; PhD, Zagreb, Croatia, 1982

    Role of MdmX in Cell Transformation and Tumorigenesis

    Photo: Zdenka Matijasevic MdmX is p53-binding proteins that functions as critical negative regulator of p53 activity in embryonic and adult tissue. Embryonic lethality caused by the loss of MdmX is completely rescued in p53-null background. Overexpression of MdmX was reported to inhibit p53 tumor suppressor functions in vitro, and amplification of MdmX is observed in variety of human cancers retaining wildtype p53. In contrast to the proposed oncogenic ability of overexpressed MdmX in p53 wildtype background, we found that MdmX suppresses tumorigenesis in mice deleted for p53 (Matijasevic, Steinman et al., 2008; Matijasevic et al., 2008). Loss of MdmX increases proliferation and spontaneous transformation of hyperploid p53-null cells in vitro. Increased proliferation correlates with reduction in chromosome number and with elevated multipolar mitotic spindle formation (see image) in both mouse embryonic fibroblasts and tumor cells. We now investigate molecular mechanisms involved in MdmX-mediated centrosome clustering that facilitates bipolar mitosis and its role in suppression of proliferation and tumorigenesis

    Cellular Responses to Hypothermia

    Mild hypothermia (28°C) increases the levels of tumor suppressor p53 protein in human fibroblasts and causes a p53-dependent cell cycle arrest in mouse fibroblasts; (Matijasevic et al., 1998). These findings suggest two areas of hypothermia application, cancer treatment and protection from environmental carcinogens.

    Hypothermia and Cancer Treatment

    Since many human tumors lack wild type p53 function, hypothermia may provide conditions for selective targeting of tumor cells; cell cycle arrest of normal cells at low temperature may protect them from cytotoxicity of drugs that target proliferating cells. Indeed, we found that, in contrast to p53-deficient cells, p53 wildtype cells survive much higher doses of drug 5-fluorouracil when incubated at 28°C than at 37°C (Matijasevic, 2002). Therefore, hypothermia may improve the therapeutic index of chemotherapy by the mechanisms based on the differences in cell cycle regulation between normal and tumor cells.

    Hypothermia and DNA Damage/Repair

    Acute and delayed toxicities from exposure to DNA-damaging agents such as sulfur mustard (SM) can be prevented or diminished by the activities of cellular DNA repair processes. At least two DNA repair mechanisms act upon SM-damaged DNA: base excision repair (BER) (Matijasevic et al., 1996) and nucleotide excision repair (NER) (Matijasevic et al., 2001). Surprisingly, activity of the first enzyme on BER pathway, DNA glycosylase, sensitizes cells to mustards (Matijasevic and Volkert, 2007). Low temperature improves recovery after the exposure to SM and the main component of this hypothermia-induced protection appears to be the inhibition of glycosylase activity.


    p53 null and MdmX/p53 null

    MdmX prevents formation of multipolar spindles in p53-null cells.

    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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    1. Matijasevic Z, Krzywicka-Racka A, Sluder G, Gallant J, Jones SN. The Zn-finger domain of MdmX suppresses cancer progression by promoting genome stability in p53-mutant cells. Oncogenesis. 2016 Oct 03; 5(10):e262. PMID: 27694836.
      View in: PubMed
    2. MatijaĊĦevic Z, Zeiger E. Marija Alacevic (April 19, 1929-February 25, 2015). Mutat Res Genet Toxicol Environ Mutagen. 2015 Jun; 784-785:45-6. PMID: 26046976.
      View in: PubMed
    3. Lyle S, Hoover K, Colpan C, Zhu Z, Matijasevic Z, Jones SN. Dicer cooperates with p53 to suppress DNA damage and skin carcinogenesis in mice. PLoS One. 2014; 9(6):e100920. PMID: 24979267.
      View in: PubMed
    4. Matijasevic Z, Krzywicka-Racka A, Sluder G, Jones SN. MdmX regulates transformation and chromosomal stability in p53-deficient cells. Cell Cycle. 2008 Oct; 7(19):2967-73. PMID: 18818521.
      View in: PubMed
    5. Matijasevic Z, Steinman HA, Hoover K, Jones SN. MdmX promotes bipolar mitosis to suppress transformation and tumorigenesis in p53-deficient cells and mice. Mol Cell Biol. 2008 Feb; 28(4):1265-73. PMID: 18039860.
      View in: PubMed
    6. Matijasevic Z, Volkert MR. Base excision repair sensitizes cells to sulfur mustard and chloroethyl ethyl sulfide. DNA Repair (Amst). 2007 Jun 1; 6(6):733-41. PMID: 17292678.
      View in: PubMed
    7. Li Q, Wright SE, Matijasevic Z, Chong W, Ludlum DB, Volkert MR. The role of human alkyladenine glycosylase in cellular resistance to the chloroethylnitrosoureas. Carcinogenesis. 2003 Mar; 24(3):589-93. PMID: 12663522.
      View in: PubMed
    8. Matijasevic Z. Selective protection of non-cancer cells by hypothermia. Anticancer Res. 2002 Nov-Dec; 22(6A):3267-72. PMID: 12530074.
      View in: PubMed
    9. Bonanno K, Wyrzykowski J, Chong W, Matijasevic Z, Volkert MR. Alkylation resistance of E. coli cells expressing different isoforms of human alkyladenine DNA glycosylase (hAAG). DNA Repair (Amst). 2002 Jul 17; 1(7):507-16. PMID: 12509225.
      View in: PubMed
    10. Matijasevic Z, Precopio ML, Snyder JE, Ludlum DB. Repair of sulfur mustard-induced DNA damage in mammalian cells measured by a host cell reactivation assay. Carcinogenesis. 2001 Apr; 22(4):661-4. PMID: 11285203.
      View in: PubMed
    11. Ludlum DB, Li Q, Matijasevic Z. Role of base excision repair in protecting cells from the toxicity of chloroethylnitrosoureas. IARC Sci Publ. 1999; (150):271-7. PMID: 10626227.
      View in: PubMed
    12. Matijasevic Z, Snyder JE, Ludlum DB. Hypothermia causes a reversible, p53-mediated cell cycle arrest in cultured fibroblasts. Oncol Res. 1998; 10(11-12):605-10. PMID: 10367942.
      View in: PubMed
    13. Matijasevic Z, Stering A, Niu TQ, Austin-Ritchie P, Ludlum DB. Release of sulfur mustard-modified DNA bases by Escherichia coli 3-methyladenine DNA glycosylase II. Carcinogenesis. 1996 Oct; 17(10):2249-52. PMID: 8895496.
      View in: PubMed
    14. Niu T, Matijasevic Z, Austin-Ritchie P, Stering A, Ludlum DB. A 32P-postlabeling method for the detection of adducts in the DNA of human fibroblasts exposed to sulfur mustard. Chem Biol Interact. 1996 Mar 8; 100(1):77-84. PMID: 8599857.
      View in: PubMed
    15. Volkert MR, Hajec LI, Matijasevic Z, Fang FC, Prince R. Induction of the Escherichia coli aidB gene under oxygen-limiting conditions requires a functional rpoS (katF) gene. J Bacteriol. 1994 Dec; 176(24):7638-45. PMID: 8002588.
      View in: PubMed
    16. Matijasevic Z, Boosalis M, Mackay W, Samson L, Ludlum DB. Protection against chloroethylnitrosourea cytotoxicity by eukaryotic 3-methyladenine DNA glycosylase. Proc Natl Acad Sci U S A. 1993 Dec 15; 90(24):11855-9. PMID: 8265637.
      View in: PubMed
    17. Matijasevic Z, Sekiguchi M, Ludlum DB. Release of N2,3-ethenoguanine from chloroacetaldehyde-treated DNA by Escherichia coli 3-methyladenine DNA glycosylase II. Proc Natl Acad Sci U S A. 1992 Oct 1; 89(19):9331-4. PMID: 1409640.
      View in: PubMed
    18. Matijasevic Z, Hajec LI, Volkert MR. Anaerobic induction of the alkylation-inducible Escherichia coli aidB gene involves genes of the cysteine biosynthetic pathway. J Bacteriol. 1992 Mar; 174(6):2043-6. PMID: 1312537.
      View in: PubMed
    19. Ludlum DB, Habraken Y, Carter CA, Matijasevic Z. The formation and enzymatic repair of DNA modifications caused by the haloethylnitrosoureas and related compounds. Nucleic Acids Symp Ser. 1992; (27):25-6. PMID: 1289818.
      View in: PubMed
    20. Matijasevic Z, Bodell WJ, Ludlum DB. 3-Methyladenine DNA glycosylase activity in a glial cell line sensitive to the haloethylnitrosoureas in comparison with a resistant cell line. Cancer Res. 1991 Mar 1; 51(5):1568-70. PMID: 1997198.
      View in: PubMed
    21. Matijasevic Z, Zeiger E. DNA binding and mutagenicity of ethyl methanesulfonate in wild-type and uvrB cells of Salmonella typhimurium. Mutat Res. 1988 Mar; 198(1):1-8. PMID: 3280980.
      View in: PubMed
    22. Matijasevic Z, Zeiger E. Mutagenicity of pyrene in Salmonella. Mutat Res. 1985 Apr; 142(4):149-52. PMID: 3885017.
      View in: PubMed
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