Eugenia Broude, Ph.D.
Senior Scientist, Ordway Research Institute
Associate Director of Cancer Center, Ordway Research Institute
Adjunct Associate Professor of Medicine, Albany Medical College

Molecular Oncology Laboratory

Telephone: (518) 641-6470
Fax: (518) 641-6305
broude@ordwayresearch.org

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 cell death that occurs as a consequence of abnormal mitosis – 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

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.

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.

B.D. Chang, E. V. Broude, J. Fang, T. V. Kalinichenko, R. Abdryashitov, J. C. Poole, and I. B. Roninson. p21^{waf1/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.

B.D. Chang, E. V. Broude, K. Watanabe, J. Fang, J. C. Poole, T. V. Kalinichenko, and I. B. Roninson. (2000) Effects of p21^{WAF1/CIP1/SDI1} on Cellular Gene Expression: Implications for Carcinogenesis, Senescence and Age-Related Diseases. Proc. Natl. Acad. Sci., U.S.A., 97: 4291-4296.

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.

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