Our laboratory studies the effects of anticancer drugs and ionizing radiation on the mammalian cell cycle, including the role of cell cycle checkpoints in tumor cell susceptibility to treatment and damage-induced perturbations of the cell cycle, especially mitosis; cellular and molecular mechanisms of mitotic catastrophe (abnormal mitosis that leads to eventual cell death or senescence), which is induced by DNA-damaging agents and by damage-inducible cyclin-dependent kinase inhibitor proteins in normal and tumor cells. In recent years, the main focus of my studies was on the role of transcription-regulating kinase CDK8 and its interactive proteins in breast cancer.
These studies combine methods of cell biology, pharmacology, experimental oncology in animal models and molecular genetics with advanced fluorescence and live video microscopy and flow cytometry techniques. Elucidation of the mechanisms of cell cycle perturbation, stress-induced transcription and treatment-induced adaptation and resistance should help in developing new drugs, improving the efficacy of existing anticancer agents, developing new agents and understanding the basic mechanisms of cancer control.
Master of Science
Kiev State University, 1983
Doctor of Philosophy
Ukrainian Academy of Sciences, Kiev, Ukraine, Ph.D., 1990
Postdoctoral Fellowship, Molecular Biology, Neuroscience
National Institute of Child Health & Human Development, NIH, Bethesda, MD, 1991-1994
- Role of transcription-regulating kinases in cancer
- Breast cancer targeted therapy
- Effects of anticancer drugs
- Tumor microenvironment and metastasis
- Broude, E.V., McAtee, M., Kelley, M.S., and Bregman, B.S. Fetal spinal cord transplants and exogenous neurotrophic support enhance the c-Jun expression in mature axotomized neurons after spinal cord injury. (1999). Experimental Neurology, 155, 65-78.
- Chang, B.D., Broude, E.V., Fang, J., Kalinichenko, T.V., Abdryashitov, R., Poole, J.C., and Roninson, I.B. p21waf1/cip1/sdi1-induced growth arrest is associated with depletion of mitosis-control proteins and leads to abnormal mitosis and endoreduplication in recovering cells. (2000). Oncogene, 19: 2165-2170.
- Chang, B.D., Broude, E.V., Watanabe, K., Fang, J., Poole, J.C., Kalinichenko, T.V., and Roninson, I.B. (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.
- Roninson, I.B., Chang, B.D., and Broude, E. (2001). Non-apoptotic responses to anticancer agents: mitotic catastrophe, senescence, and the role of p53 and p21. In: Cell Cycle Checkpoints and Cancer, Mikhail V. Blagosklonny, Ed., Landes Bioscience, Georgetown, TX, pp. 196-207.
- Chang, B.D., Swift, M.E., Shen, M., Fang, J., Broude, E.V., and Roninson, I.B. (2002). Molecular determinants of terminal growth arrest induced in tumor cells by a chemotherapeutic drug. Proc. Natl. Acad. Sci. USA 99, 389-394.
- Broude, E.V., Demidenko, Z.N., Vivo, C., Swift, M.E., Davis, B.M., Blagosklonny, M.V., Roninson I.B. p21 (CDKN1A) is a negative regulator of p53 stability. (2007). Cell Cycle 6, 1468-1471.
- Broude, E.V., Swift, M.E., Vivo, C., Chang, B.D., Davis, B.M., Kalurupalle, S., Blagosklonny, M.V., Roninson, I.B. p21Waf1/Cip1/Sdi1 mediates retinoblastoma protein degradation. (2007). Oncogene. Oct 18; 26(48):6954-8.
- 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.
- 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.
- 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 short hairpin RNA library and massive parallel sequencing. Proc. Natl. Acad. Sci. USA, 107, 7377-7382.
- Shtutman, M., Baig, M., Levina, E., Hurteau, G., Lim, C., Broude, E.V., Nikiforov, M.A., Harkins, T.T., Carmack, C.S., Ding, E. Wieland, F., Buttyan, R., and Roninson, I.B. (2011). Tumor cell survival is dependent on a coat protein subunit COPZ1 due to the silencing of its isoform COPZ2. Proc. Natl. Acad. Sci. USA, 108, 12449-54.
- Gonzales, R.E., Lim, C., Cole, K., Bianchini, C.H., Schools, G.P., Davis, B.E., Wada, I., Roninson, I.B., and Broude, E.V. Effects of conditional depletion of topoisomerase II on cell cycle progression in mammalian cells. Cell Cycle, 2011, Oct 15; 10(20), 3505-3514.
- Levina E, Ji H, Chen M, Baig M, Oliver D, Ohouo P, Lim CU, Schools G, Carmack S, Ding Y, Broude EV, Roninson IB, Buttyan R, Shtutman M. Identification of novel genes that regulate androgen receptor signaling and growth of androgen-deprived prostate cancer cells. Oncotarget. 2015 May 30; 6(15):13088-104.
- Broude EV*, Győrffy B, Chumanevich A, Chen M, McDermott MS, Shtutman, M., Catroppo, J.F., Roninson, I.B. (2015). Expression of CDK8 and CDK8-interacting genes as potential biomarkers in breast cancer. Current Cancer Drug Targets, 2015, Vol. 15, No. 8.