Last Updated: 5/11/2005

Research Interests
One of the most fundamental aspects of animal development is the control of the cell division cycle. Without this control there would be no coordination between cell proliferation and the formation of the gross anatomy of an organism. In my laboratory we are interested in understanding how the molecular processes that establish pattern formation and determine cell fates during development control the cell cycle. We use genetic and biochemical approaches to examine how specific cell cycle regulators (e.g. E2F, cyclins, cdks) function, and then use this information to explore how their activity is influenced by different developmental programs. In the past several years it has become apparent that the structure and function of molecules controlling the cell cycle are highly conserved between mammals and Drosophila. This allows us to exploit certain advantages that Drosophila has over mammalian systems for studying growth control and cell cycle regulation. One important advantage is the ease with which molecular genetic approaches can be applied to the study of gene function in the context of the whole animal. Another is the relative simplicity of fruit flies: the study of many mammalian cell cycle regulators is complicated by the existence of gene families whose members have overlapping or redundant functions, whereas the Drosophilia homologs of these molecules are often encoded by single genes. Genetic analyses of these genes in Drosophila provide a powerful tool for understanding the fundamental roles of cell cycle regulators in controlling cell proliferation. In this way Drosophila can contribute important information for understanding aspects of the deregulated growth typical of cancer. Our research involves several different projects aimed at understanding the G1-S transition of the cell cycle, including the control of gene expression by E2F and the pRB tumor suppressor, expression of replication dependent histone mRNAs, and ubiquitin mediated proteolysis of cell cycle regulators.

Recent Accomplishments and Honors
1997 Damon Runyon Scholar Award
2000 NSF Career Award
2003 UNC Ruth and Phillip Hettleman Prize for Artistic and Scholarly Achievement

Training
1986 B.S. Massachusetts Institute of Technology, Cambridge, MA

1991 Ph.D. Washington University, St. Louis, MO

1986-1991 Graduate Research with Dr. Jeffrey I. Gordon, Head, Department of Molecular Biology and Pharmacology, Washington University, St Louis, MO.

1992-1996 Damon Runyon-Walter Winchell Cancer Research Fund Postdoctoral Fellow with Dr. Patrick H. O'Farrell, Professor of Biochemistry and Biophysics, University of California, San Francisco, CA.

Publications
Donaldson, T. D., Noureddine, M.A., Reynolds, P. J., Bradford, W., and Duronio, R.J. Targeted disruption of Drosophila Roc1b reveals functional differences in the Roc subunit of Cullin-dependent E3 Ubiquitin Ligases. Mol. Biol Cell in press (2004).

Lanzotti, D. J., Kupsco, J. M., Marzluff, W. F., and Duronio, R. J. stringcdc25 and cyclin E are required for patterned histone expression at different stages of Drosophila embryonic development. Dev. Biol. 274, 82-93 (2004).

Duronio, R. J. A Breath of Fresh Air for Cyclin D/Cdk4; Triggering Growth via Hph. Dev Cell. 6, 163-164 (2004).

Lanzotti, D. J., Kupsco, J. M., Yang, X.-C., Dominski, Z., Marzluff, W. F., and Duronio, R. J. Drosophila SLBP intracellular localization is mediated by phosphorylation and is required for cell cycle-regulated histone mRNA expression. Mol. Biol. Cell 15, 1112-1123 (2004).

Donaldson, T. D. and Duronio, R. J. Cancer cell biolog: Myc wins the competition. Curr. Biol. 14, R425-427 (2004)

Thacker, S., Bonnette, P. C., and Duronio, R. J. The contribution of E2F-regulated transcription to Drosophila PCNA function. Curr Biol 13, 53-58 (2003).

Cayirlioglu, P. Ward, W. O., Silver Key, S. C., and Duronio, R. J. Transcriptional repressor functions of Drosophila E2F1 and E2F2 cooperate to inhibit genomic DNA synthesis in ovarian follicle cells. Mol. Cell. Biol. 23, 2123-2134 (2003).

Noureddine, M.A., Donaldson, T. D., Thacker, S.A. and Duronio, R.J. Drosophila Roc1a encodes a RING-H2 protein with a unique function in processing the Hh signal transducer Ci by the SCF E3 ubiquitin ligase. Dev. Cell 2, 757-770 (2002)

Lanzotti, D.J., Kaygun, H., Yang, X., Duronio, R.J., and Marzluff, W.F. Developmental control of histone mRNA and dSLBP synthesis during Drosophila embryogenesis and the role of dSLBP in histone mRNA 3' end processing in vivo. Mol Cell Biol., 22, 2267-2282 (2002).

Cayirlioglu, P., Bonnette, P.C., Dickson, M.R., and Duronio, R. J. Drosophila dE2F2 Promotes the Conversion from Genomic DNA Replication to Gene Amplification in Ovarian Follicle Cells. Development, 128, 5085-5098 (2001).

Sullivan, E., Santiago, C., Parker, E.D., Dominski, Z., Yang, X., Lanzotti, D.J., Ingledue, T.C., Marzluff, W.F., and Duronio, R.J. Drosophila stem loop binding protein coordinates accumulation of mature histone mRNA with cell cycle progression. Genes & Dev., 15, 173-187 (2001).

Myster, D. L., Bonnette, P. C., and Duronio, R. J. (2000) A Role for the DP Subunit of the E2F Transcription Factor in Axis Determination During Drosophila Oogenesis, Development, 127, 3249-3261.

Duronio, R.J., Bonnette, P.C., and O’Farrell, P.H. Mutations of the Drosophila dDP, dE2F, and cyclin E genes reveal distinct roles for the E2F/DP transcription factor and cyclin E during the G1-S transition. Mol. Cell. Biol., 18, 141-151 (1998).

Duronio, R. J. and O’Farrell, P.H. Developmental control of the G1-S transition in Drosophila: Cyclin E is a limiting downstream target of E2F, Genes & Dev., 9, 1456-1468 (1995).

E-mail: duronio@med.unc.edu
Telephone: (919) 962-7749
FAX: (919) 962-8472
Address: 307 Fordham Hall, CB# 3280 Chapel Hill, NC
URL: http://www.bio.unc.edu/faculty/duronio/lab/

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