MICaB Graduate Program
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Martina Bazzaro, Ph.D.
Department of Obstetrics, Gynecology and Women’s Health and Masonic Cancer Center
University of Ferrara, Italy, Ph.D. 2001
Study of the mechanisms underlying breast and ovarian cancer development and progression
My laboratory is interested in studying abnormalities of protein degradation pathways in breast and ovarian cancer. The Ubiquitin-Proteasome-System (UPS) is responsible for degradation of over 90% of short-lived intracellular proteins. Protein degradation through Ubiquitin-Proteasome-System is a multistep process that begins with de-ubiquitination of ubiquitin-tagged target molecules by de-ubiquitinating enzymes following their entrance in the 20S catalytic chamber of the proteasomes were the actual degradation occurs. The polypeptide targets of the proteasome include proteins involved in cell cycle progression, survival and inflammation and while the ubiquitin-dependent proteasomal degradation is crucial for both normal and malignant cells the higher demand for metabolic/catabolic activity associated with the malignant phenotype renders the ubiquitin-proteasome pathway a suitable tool for cancer treatment. My laboratory is particularly interested in studying the role played by proteasomal- and lysosomal-assisted protein degradation pathways during the development and the progression of breast and ovarian cancer and in the development of new small-molecules inhibitors of ubiquitin-proteasome-system for targeting breast and ovarian cancer cells.
Selected Recent Publications:
- Lin Z.*, Bazzaro M*, Peng SW, and Roden RBS. Combination of Proteasome and HDAC6 Inhibitors for Therapy of Uterine Cervical Cancer. Clinical Cancer Research. 15;15(2):570-7, 2009. (* Equal contribution).
- Bazzaro M, Lin Z, Santillan A, Lee MK, Wang MC, Chan KC, Bristow RE, Mazitschek R, Bradner J, and Roden RBS. Ubiquitin Proteasome System Stress Underlies Synergistic Killing of Ovarian Cancer Cells by Bortezomib and a Novel HDAC6 Inhibitor. Clinical Cancer Research, 15;14(22):7340-7, 2008 (Journal Cover).
- Bazzaro M, Santillan A, Lin Z, Tang T, Lee MK, Bristow RE, Shih IeM, Roden RB. Myosin II Co-chaperone General Cell UNC-45 Overexpression is Associated with Ovarian Cancer, Rapid Proliferation, and Motility. American Journal of Pathology 171(5): 1640-1649, 2007.
- Bazzaro M, Lee MK, Zoso A, Stirling W, Santillan A, Shih IE and Roden R.B.S. Ubiquitin-Proteasomal System Stress Sensitizes Ovarian Cancer to Proteasome Inhibitor-Induced Apoptosis. Cancer Research, 66(7): 3754-63, 2006.
- Marastoni M, Bazzaro M, Bortolotti F, Tomatis R. Synthesis and activity of N-benzyl pseudopeptides HIV protease inhibitors. Bioorg. Med. Chem. 11(11) 2477-83, 2003.
- Marastoni M, Bazzaro M, Micheletti F, Gavioli R, Tomatis R. Cytotoxic T lymphocyte epitope analogues containing cis- or trans-4-aminocyclohexanecarboxylic acid residues. Bioorg Med. Chem. 10 (9): 3061-6, 2002.
- Vertuani S, Bazzaro M, Gualandi G, Micheletti F, Marastoni M, Canella A, Marino M, Tomatis R, Traniello S, and Gavioli R. Effect of interferon-alpha therapy on epitope-specific cytotoxic T lymphocyte responses in hepatitis C virus-infected individuals. Eur. J. Immunol. 32:144-154, 2002
- Marastoni M, Bazzaro M, Micheletti F, Gavioli R, Tomatis R. Peptide analogues of a subdominant epitope expressed in EBV associated tumors: synthesis and immunological activity. J. Med. Chem. 44:2370-2373, 2001.
- Marastoni M, Bazzaro M, Bortolotti F, Tomatis M. Synthesis and activity of new acylated diaminohydroxy- alkanes as human immunodeficiency virus protease inhibitors. Arzneim.—Forsch./ Drug Res.50:564-568, 2000.
- Marastoni M, Bazzaro M, Gavioli R, Micheletti F, Traniello S, and Tomatis R. Design of dimeric peptides obtained from subdominant Epstein-Barr virus LMP2-derived epitope. Eur. J. Med.Chem. 35:1-6, 2000.
- Marastoni M, Bazzaro M, Salvadori S, Bortolotti F, Tomatis R. HIV-1 protease inhibitors containing an N-hydroxyamino acid core structure. Bioorg. Med. Chem. 9: 939-945, 2000.
- Marastoni M, Bazzaro M, Bortolotti F, Salvadori S, Tomatis R. Symmetry-based inhibitors of HIV-protease. Design, synthesis and preliminary structure-activity studies of acylated 2,3-diamino-1-hydroxypropanes and 2,4 diamino-1-hydroxybutanes. Eur. J. Med. Chem.34: 651-657, 1999.
- Micheletti F, Bazzaro M, Canella A, Marastoni M, Tomatis R, Traniello S, Gavioli S. The lifespan of major histocompatibility complex class I/peptide complexes determines the efficiency of cytotoxic T lymphocyte responses. Immunology 96: 411-415, 1999.