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INVESTIGATOR PROFILES

Eugenia Broude, Ph.D.

SENIOR SCIENTIST
 Ordway Research Institute

ASSOCIATE DIRECTOR
Cancer Center,
Ordway Research Institute

ADJUNCT ASSOCIATE PROFESSOR OF MEDICINE
 Albany Medical College

CONTACT
Molecular Oncology Laboratory
Phone: (518) 641-6470
Fax: (518) 641-6305
broude@ordwayresearch.org

Eugenia Broude, Ph.D.

Research Focus

Dr. Broude’s team is studying cellular and molecular mechanisms of mitotic catastrophe induced by DNA-damaging agents and cyclin-dependent kinase inhibitors, in normal and tumor cells that differ in the status of different cell cycle checkpoints.

Mitotic catastrophe – defined as abnormal mitosis that leads to cell death or irreversible cell cycle arrest – is one of the principal antiproliferative effects of almost all anticancer agents, regardless of whether such agents affect the cell cycle in mitosis or in interphase. Normal cells avoid mitotic catastrophe by activating different cell cycle checkpoints, which allow the cell to repair the damage prior to entering mitosis. Tumor cells, however, are always deficient in some of the cell cycle checkpoints. This deficiency increases the likelihood that tumor cells would enter mitosis before repairing the damage and thereby undergo mitotic catastrophe. In contrast to treatment-induced physiological antiproliferative responses, such as apoptosis and senescence, mitotic catastrophe is potentiated rather than inhibited by cellular changes that develop in the course of neoplastic transformation. It is therefore a major mechanism of tumor selectivity for clinically useful anticancer agents.

The analysis of mitotic catastrophe by Dr. Broude’s team involves:

  • Molecular genetic approaches to manipulating cell cycle checkpoints
  • Confocal and fluorescence microscopy
  • 4D live-cell imaging
  • Flow cytometric analysis of the cell cycle
  • Analysis of expression and localization of different proteins involved in mitosis
  • Isolation and characterization of cell lines resistant to different forms of mitotic catastrophe

Elucidation of the mechanisms of treatment-induced mitotic catastrophe in tumor cells should help in developing new drugs and improving the efficacy of existing anticancer agents.

Selected Publications (View)

  • 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.
  • Demidenko, Z.N., Kalurupalle, S., Hanko, C., Lim, C.U., Broude, E., Blagosklonny, M.V. (2008). Mechanism of G1-like arrest by low concentrations of paclitaxel: next cell cycle p53-dependent arrest with sub G1 DNA content mediated by prolonged mitosis. Oncogene. 2008 Jul 24;27(32):4402-10
  • Roninson, I.B. and Broude, E.V. (2008). Treatment-induced tumor cell senescence and its consequences. In "Beyond Apoptosis: How Anticancer Agents Stop the Growth of Tumor Cells", I.B. Roninson, J.M. Brown and D.E. Bredesen, Editors, Informa Healthcare, pp. 223-249.
  • Broude, E.V., Loncarek, J., Wada, I., Cole, K., Hanko, C., Swift, M. and Roninson, I.B. (2008). Mitotic catastrophe in cancer therapy. In "Beyond Apoptosis: How Anticancer Agents Stop the Growth of Tumor Cells", I.B. Roninson, J.M. Brown and D.E. Bredesen, Editors, Informa Healthcare, pp.307-320.
  • Broude, E.V., Demidenko, Z.N., Vivo, C., Swift, M.E., Davis, B.M., Blagosklonny, M.V., and Roninson, I.B. (2007). p21 (CDKN1A) is a negative regulator of p53 stability. Cell Cycle 6,1468-1471.
  • Broude, E.V., Swift, M.E., Vivo, C., Chang, B.-D., Davis, B.M., Kalurupalle, S., Blagosklonny, M.V., and Roninson, I.B. (2007). p21Waf1/Cip1/Sdi1 mediates retinoblastoma protein degradation. Oncogene 26, 6954-6958.
  • I.B. Roninson, E.V. Broude, and B.D. Chang (2001). If Not Apoptosis, Then What? Treatment-Induced Senescence and Mitotic Catastrophe in Tumor Cells. Drug Resistance Updates, 4: 303-313.
  • B.D. Chang, E. V. Broude, K. Watanabe, J. Fang, J. C. Poole, T. V. Kalinichenko, and I. B. Roninson. (2000) Effects of p21WAF1/CIP1/SDI1 on Cellular Gene Expression: Implications for Carcinogenesis, Senescence and Age-Related Diseases. Proc. Natl. Acad. Sci., U.S.A., 97: 4291-4296.
  • B.D. Chang, E. V. Broude, J. Fang, T. V. Kalinichenko, R. Abdryashitov, J. C. Poole, and I. B. Roninson. p21waf1/cip1/sdi1-induced growth arrest is associated with depletion of mitosis-control proteins and leads to abnormal mitosis and endoreduplication in recovering cells. Oncogene, 2000, 19: 2165-2170.
  • Broude, E.V., M. McAtee, M.S. Kelley and B.S. Bregman. Fetal spinal cord transplants and exogenous neurotrophic support enhance the c-Jun expression in mature axotomized neurons after spinal cord injury. Experimental Neurology, 1999, 155: 65-78.
  • Broude, E.V. M. McAtee, M. S. Kelley and B. S. Bregman. C-Jun expression in adult rat dorsal root ganglion neurons: differential response of CNS and PNS after axonal injury, Experimental Neurology, 1997, 148: 367-377.