Contact Information

University Of Illinois at Chicago

Dept. Of Biochemistry and

Molecular Genetics

900 S. Ashland (M/C 669)
Chicago, IL 60607
tel: 312-996-7670
fax: 312-413-0353

Research Interests:

The research in our lab is focused on understanding the molecular mechanisms of the cell cycle regulation and how these mechanisms are utilized in vivo. Many models attribute a central role in cell cycle regulation to a transcriptional factor E2F and Retinoblastoma tumor suppressor protein (pRB). Importantly, the pRB pathway is functionally inactivated in most tumor cells and it is thought that unrestrained activity of E2F drives inappropriate proliferation in tumors. There has been a significant progress in recent years toward the understanding of the biochemical properties of E2F and pRB proteins and the ways they are regulated. However, the mechanisms by which pRB negatively controls cell proliferation in vivo are not fully understood. Genetically, Drosophila provides a relatively simpler system to study the role of E2F, since the corresponding families are smaller. Our lab is carrying out large scale unbiased genetic screens to identify new genes that interface with the E2F/pRB module in vivo and contribute to its regulation during development.

We are also interested in dissecting functional interactions between the pRB pathway and other tumor suppressor pathways. Particularly, our focus is on the recently identified Hippo tumor suppressor pathway which negatively regulates organ size in flies and mammals. Given the pivotal role of pRB in tumor suppression, an understanding of how the function of the Drosophila homologues dE2F/pRB is regulated will provide crucial clues in understanding the regulation of mammalian cell growth and the ways in which such controls may go awry in human cancer.

Selected Publications:

Frolov, M.V., D.S. Huen, O. Stevaux, D. Dimova, K. Balczarek-Strang, and N.J. Dyson. 2001. Functional antagonism between E2F family members. Genes & Development15: 2146-2160.

Frolov M.V., O. Stevaux, N.S. Moon, D. Dimova, E.J. Kwon, E.J. Morris, and N.J. Dyson. 2003.  G1 cyclin-dependent kinases are insufficient to reverse dE2F2-mediated repression. Genes & Development17: 723-728. 

Frolov, M.V. and N.J. Dyson. 2004. Molecular mechanisms of E2F-dependent activation and pRB-mediated repression. Journal of Cell Science117: 2173-2181.

Frolov M.V., N.S. Moon, and N.J. Dyson. 2005. DP is needed for normal cell proliferation. Molecular and Cellular Biology.25: 3027-3039.

Moon N.S., M.V. Frolov, E.J. Kwon, L. Di Stefano, D.K. Dimova, E.J. Morris, B. Taylor-Harding, K. White, and N.J. Dyson. 2005. Drosophila E2F1 has context-specific pro- and antiapoptotic properties during development. Developmental Cell. 9: 463-475.

Rasheva, V.I., D. Knight, P. Bozko, K. Marsh, and M.V. Frolov. 2006. Specific role of the SR protein splicing factor B52 in cell cycle control in Drosophila. Molecular and Cellular Biology.26: 3468-3477.

Ambrus, A. M., B. N. Nicolay, V. I. Rasheva, R. Suckling, and M.V. Frolov. 2007. dE2F2-independent rescue of proliferation in cells lacking an activator dE2F1. Molecular and Cellular Biology.27: 8561-8570.

Nicolay, B. N. and M.V. Frolov. 2008. Context dependent requirement for dE2F during oncogenic proliferation. PLoS Genetics, 4: e1000205.

Ambrus, A.M., B.N. Nicolay, V.I. Rasheva and M.V. Frolov. 2009. Mosaic genetic screen for suppressors of the de2f1 mutant phenotype in Drosophila. Genetics.183: 79-92.

Nicholson, S.C., M.M. Gilbert, B.N. Nicolay, M.V. Frolov and K.H. Moberg. 2009. The archipelago tumor suppressor limits Rb/E2F-regulated apoptosis in developing Drosophila tissues. Current Biology.19: 1503–1510.

Ambrus, A.M. and M.V. Frolov. 2009. The diverse roles of RNA helicases in RNAi. Cell Cycle. 8: 3500 - 3505.

Ambrus, A.M. and M.V. Frolov. 2010. Mutation of the DEAD-box helicase belle down-regulates the cyclin-dependent kinase inhibitor Dacapo. Cell Cycle. 9: 1016 – 1020.

Nicolay, B.N., B. Bayarmagnai, N.S. Moon, E.V. Benevolenskaya and M.V. Frolov. 2010. Combined inactivation of pRB and Hippo pathways induces dedifferentiation in the Drosophila retina. PLoS Genetics. 6: e1000918.

Hsieh, T.-C., B.N. Nicolay, M.V. Frolov, and N.S. Moon. 2010. Tuberous Sclerosis Complex 1 regulates dE2F1 expression during development and cooperates with RBF1 to control proliferation and survival. PLoS Genetics. 6: e1001071.

Nicholson, S.C., B.N. Nicolay, M.V. Frolov, and K.H. Moberg. 2011. Notch-dependent expression of the archipelago ubiquitin ligase subunit in the Drosophila eye. Development. 138: 251-260.

Nicolay, B.N., B. Bayarmagnai, A.B. Islam, N. Lopez-Bigas and M.V. Frolov. 2011. Cooperation between dE2F1 and Yki/Sd defines a distinct transcriptional program necessary to bypass cell cycle exit. Genes & Development.25: 323-335.

Truscott, M., A.B. Islam, N. Lopez-Bigas and M.V. Frolov. 2011. mir-11 limits the pro-apoptotic function of its host gene, dE2f1. Genes & Development.25: 1820-1834.