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Zdenka Matijasevic PhD

TitleAssistant Professor
InstitutionUMass Chan Medical School
DepartmentPediatrics
AddressUMass Chan Medical School
55 Lake Avenue North
Worcester MA 01655
Phone508-856-2459
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    Other Positions
    InstitutionT.H. Chan School of Medicine
    DepartmentPediatrics

    InstitutionMorningside 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 Summary
    Currently running Stem Cell Facility at UMass Chen TAM Core focusing on the reprogramming of patient primary cells into the induced pluripotent stem (iPS) cells for disease modeling and drug discovery.
    Collapse overview
    Cell and Developmental Biology

    Academic Background

    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.

    Figure

    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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    PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
    1. Guo D, Daman K, Chen JJ, Shi MJ, Yan J, Matijasevic Z, Rickard AM, Bennett MH, Kiselyov A, Zhou H, Bang AG, Wagner KR, Maehr R, King OD, Hayward LJ, Emerson CP. iMyoblasts for ex vivo and in vivo investigations of human myogenesis and disease modeling. Elife. 2022 01 25; 11. PMID: 35076017.
      Citations: 3     Fields:    Translation:HumansAnimalsCells
    2. MatijaĊĦevi? Z, Zeiger E. Marija Ala?evi? (April 19, 1929-February 25, 2015). Mutat Res Genet Toxicol Environ Mutagen. 2015 Jun; 784-785:45-6. PMID: 26046976.
      Citations:    Fields:    Translation:HumansCells
    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.
      Citations: 9     Fields:    Translation:Animals
    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.
      Citations: 18     Fields:    Translation:HumansAnimalsCells
    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.
      Citations: 32     Fields:    Translation:AnimalsCells
    6. Matijasevic Z, Volkert MR. Base excision repair sensitizes cells to sulfur mustard and chloroethyl ethyl sulfide. DNA Repair (Amst). 2007 Jun 01; 6(6):733-41. PMID: 17292678.
      Citations: 3     Fields:    Translation:AnimalsCells
    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.
      Citations:    Fields:    Translation:HumansCells
    8. Matijasevic Z. Selective protection of non-cancer cells by hypothermia. Anticancer Res. 2002 Nov-Dec; 22(6A):3267-72. PMID: 12530074.
      Citations: 5     Fields:    Translation:HumansAnimalsCells
    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.
      Citations: 6     Fields:    Translation:HumansCells
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