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INVESTIGATOR PROFILES

Igor B. Roninson, Ph.D.

SENIOR SCIENTIST
 Ordway Research Institute

DIRECTOR
Cancer Center,
Ordway Research Institute

RESEARCH PROFESSOR
OF BIOLOGY
Rensselaer Polytechnic Institute

ADJUNCT PROFESSOR
OF BIOLOGY
State University of
New York at Albany

ADJUNCT PROFESSOR
OF MEDICINE
 Albany Medical College

CONTACT
Molecular Oncology Laboratory
Phone: (518) 641-6471
Fax: (518) 641-6305
roninson@ordwayresearch.org

Igor B. Roninson, Ph.D.

Research Focus

The primary area of Dr. Roninson’s research is the mechanisms by which anticancer agents inhibit the proliferation of tumor cells. The first topic of investigation in this area is terminal growth arrest through the program of cell senescence. Dr. Roninson and his team have found that treatment-induced senescence of tumor cells is associated with the induction of multiple genes, which account for different aspects of the senescent phenotype. While some of these genes act as tumor suppressors, a subset of genes induced in senescent cells encode secreted factors with tumor-promoting activities. These activities are mediated in part through the induction of cyclin-dependent kinase inhibitors (CKI), such as p21 (CDKN1A). The team has found that CKI induction leads to transcriptional activation of many genes with potential pathogenic effects. These include secreted tumor-promoting factors, as well as many genes implicated in age-related diseases, such as Alzheimer’s disease, atherosclerosis or arthritis. They are investigating the regulatory mechanisms of senescence-associated changes in gene expression, with a goal of developing drugs that will promote tumor cell senescence or inhibit its undesirable side effects. The other treatment response that the Molecular Oncology Laboratory studies is mitotic catastrophe, a form of cell death that results from abnormal mitosis and that is induced in tumor cells by different classes of chemotherapeutic drugs and radiation. The team is characterizing different mechanisms of mitotic catastrophe in tumor cells and the role of cell cycle checkpoints in this process.

The second area of research in the Molecular Oncology Laboratory is the identification of genes essential for tumor cell growth. This program is based on the methodology for function-based selection of transdominant genetic inhibitors, such as genetic suppressor elements (GSE) and short hairpin RNA (shRNA). GSE are short sense- or antisense-oriented gene fragments that inhibit the function of genes from which they are derived, whereas shRNA cause the degradation of their mRNA target through the RNA interference mechanism. By isolating GSEs and shRNA that inhibit the growth of tumor cell lines, he and his team have generated a large list of genes that are required for tumor cell proliferation, and they are continuing the identification of such genes in different types of tumor and normal cells. Some of the proteins encoded by these genes are being characterized as tumor-specific targets for the next generation of anticancer drugs.

The research of the Molecular Oncology Laboratory extensively utilizes the deconvolution and confocal microscopy core resources of ORI, in particular for live-cell time-lapse microscopy, as well as the flow cytometric core and Functional Genomics Facility.

Selected Publications (View)

  • Tapias, A., Ciudad, C.J., Roninson, I.B. and Noé, V. (2008). Regulation of SP1 by cell cycle related proteins. Cell Cycle 7, 2856-2867.
  • Yates, K.E., Korbel, G.A., Shtutman, M., Roninson, I.B., and DiMaio, D. (2008). Repression of the SUMO-specific protease Senp1 induces p53-dependent premature senescence in normal human fibroblasts. Aging Cell 7, 609-621.
  • Shao, Y., Chan, C.Y., Maliyekkel, A., Lawrence, C.E., Roninson, I.B., and Ding. Y. (2007). Effect of target secondary structure on RNAi efficiency. RNA 13, 1631-1640.
  • 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.
  • Shtutman, M., Levina, E., Ohouo, P., Baig, M., and Roninson, I.B. (2006). Cell adhesion molecule L1 disrupts E-cadherin containing adherens junctions and increases scattering and motility of MCF7 breast carcinoma cells. Cancer Research, 66, 11370-11380.
  • Maliyekkel, A., Davis, B. M., and Roninson, I.B. (2006). Cell cycle arrest drastically extends the duration of gene silencing after transient expression of short hairpin RNA. Cell Cycle 5, 2390-2395.
  • Chen, Y., Dokmanovic, M.,  Stein, W.D., Ardecky, R.J., Roninson, I.B. (2006). Agonist and antagonist of retinoic acid receptors cause similar changes in gene expression and induce senescence-like growth arrest in MCF-7 breast carcinoma cells. Cancer Research, 66, 8749-8761.
  • Poole, J.C., Thain, A., Perkins, N.D., and Roninson, I.B. (2004). Induction of transcription by p21Waf1/Cip1/Sdi1: role of NFκB and effect of non-steroidal anti-inflammatory drugs. Cell Cycle 3, 931-940.
  • Nickoloff, B.J., Lingen, M.W., Chang, B.D., Shen, M., Swift, M., Curry, J., Bacon, P., Bodner, B., and Roninson, I.B. (2004). Tumor suppressor maspin is upregulated during keratinocyte senescence, exerting a paracrine anti-angiogenic activity. Cancer Res. 64, 2956-2961.
  • Primiano, T., Baig, M., Maliyekkel, A., Chang, B.D., Fellars, S., Sadhu, J., Axenovich, S., Holzmayer, T.A. and Roninson, I.B. (2003). Identification of potential anticancer drug targets through the selection of growth-inhibitory genetic suppressor elements. Cancer Cell, 4: 41-53.
  • 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.
  • Chang, B.D., Broude, E.V., Fang, J., Kalinichenko, T.V., Abdryashitov, R., Poole, J.C., and Roninson, I.B. (2000). 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 19: 2165-2170.
  • Chang, B.D., Watanabe, K., Broude, E.V., 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. USA 97: 4291-4296.
  • Chang, B.D., Broude, E.V., Dokmanovic, M., Zhu, H., Ruth, A., Xuan, Y., Kandel, E.S., Lausch, E., Christov, K. and Roninson, I.B. (1999). A senescence-like phenotype distinguishes tumor cells that undergo terminal proliferation arrest after exposure to anticancer agents. Cancer Res. 59: 3761-3767.
Selected Reviews
  • 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.
  • Shay, J.W. and Roninson, I.B. (2004). Hallmarks of senescence in carcinogenesis and cancer therapy. Oncogene, 23, 2919-2933.
  • Roninson, I.B. and Gudkov, A.V. (2003). Genetic suppressor element (GSE) methodology and its applications to characterization and identification of tumor suppressor genes. In: Methods in Molecular Medicine: Analysis of Tumor Suppressor Genes, volume I (W.S. El-Deiry, Ed.), Humana Press, pp. 411-434.
  • Roninson, I.B. (2003). Tumor cell senescence in cancer treatment. Cancer Res., 11: 2705-2715.
  • Roninson, I.B. (2002). Oncogenic functions of tumor suppressor p21Waf1/Cip1/Sdi1: association with cell senescence and tumor-promoting activities of stromal fibroblasts. Cancer Lett., 179: 1-14.
  • Roninson, I.B., Broude, E.V., and Chang, B.D. (2001). If not apoptosis, then what? Treatment-induced senescence and mitotic catastrophe in tumor cells. Drug Resistance Updates 4: 303-313.