Igor Roninson, Ph.D.

SmartState Endowed Chair in Translational Cancer Therapeutics

Director, Center for Targeted Therapeutics (CTT)

(803) 777-2623 | Office

(803) 777-0410 | Fax

roninsoni@sccp.sc.edu

Dr. Igor Roninson

Research Interests

The main research topic of our laboratory is the role of the CDK8/19 kinase in transcriptional reprogramming in the context of cancer, aging-associated diseases, inflammatory and viral diseases. CDK8 and CDK19 are closely related members of the cyclin-dependent kinase (CDK) family that, unlike some other CDKs, do not regulate cell cycle progression. Instead, CDK8 and CDK19 are alternative components of the regulatory module of the transcriptional Mediator complex, where they interact with their regulatory subunit Cyclin C and the proteins MED12 and MED13.

The principal function of CDK8/19 is to potentiate the activity of transcription-initiating factors by enabling the elongation of transcription of newly activated genes. CDK8 is an oncogene that potentiates many pro-carcinogenic transcriptional pathways but CDK8/19 inhibition has little effect on cells or organisms under homeostatic conditions. Using chemical genomics, we have identified CDK8/19 as the key “druggable” mediator of the induction of various cytokines implicated in cancer, inflammation and aging-associated diseases, in cells undergoing damage response or senescence. We have developed the first selective small-molecule inhibitors of CDK8/19 and we are using these inhibitors to study the role of this pleiotropic transcriptional regulator in different pathological processes and especially cancer growth, metastasis and resistance to therapy. We are also studying the mechanistic aspects of the interaction between CDK8/19 and different transcription-initiating factors.

Center for Targeted Therapeutics

Education

Master of Science
Virology, 1977

Moscow State University

Doctor of Philosophy
Biochemistry, 1982

Massachusetts Institute of Technology

Postdoctoral Fellowship
Molecular Biology, 1984

Massachusetts Institute of Technology

Igor the Google Scholar

Smart State - Roninson

tct

Research Highlights

Selected Publications

Pub Med

  • 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., 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.
  • 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.
  • Shtutman, M., Baig, M., Levina, E., Hurteau, G., Lim, C., Broude, E.V., Nikiforov, M.A., Harkins, T.T., Carmack, C.S., Ding, Y., Wieland, F., Buttyan, R., and Roninson, I.B. (2011). Tumor-specific silencing of COPZ2 gene encoding coatomer protein complex subunit ?2 renders tumor cells dependent on its paralogous gene COPZ1. Proc. Natl. Acad. Sci. USA, 108, 12449-12454.
  • Porter, D.C., Farmaki, E., Altilia, S., Schools, G.P., West, D.K., Chen, M., Chang, B.-d., Puzyrev, A.T., Lim, C., Rokow-Kittell, R., Friedhoff, L.T., Papavassiliou, A.P., Kalurupalle, S., Hurteau, G., Shi, J., Baran, P.S., Gyorffy, B., Wentland, M.P., Broude, E.V., Kiaris, H., and Roninson, I.B. (2012). Cyclin-dependent kinase 8 mediates damage-induced tumor-promoting paracrine activities. Proc. Natl. Acad. Sci. USA, 109, 13799-13804.

More Publications

  • Roninson, I.B., Abelson, H., Housman, D.E., Howell, N., and Varshavsky, A. (1984). Amplification of specific DNA sequences correlates with multidrug resistance in Chinese hamster cells. Nature 309, 626-628.
  • Chen, C.-j., Chin, J.E., Ueda, K., Clark, D.P., Pastan, I., Gottesman, M.M., and Roninson, I.B. (1986). Internal duplication and homology with bacterial transport proteins in the mdr1 (P-glycoprotein) gene from multidrug-resistant human cells. Cell 47, 381-389.
  • Gudkov, A.V., Kazarov, A.R., Thimmapaya, R., Axenovich, S., Mazo, I., and Roninson, I.B. (1994).  Cloning mammalian genes by expression selection of genetic suppressor elements: association of kinesin with drug resistance and cell immortalization. Proc. Natl. Acad. Sci. USA, 91, 3744-3748.
  • 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.