EDWARD B. DUBROVSKY


Edward B. Dubrovsky Associate Professor
Department of Biological Sciences Fordham University 441 East Fordham Road Bronx, NY 10458

Office: (718) 817-3660 Lab: (718) 817-3663 Fax: (718) 817-3645
dubrovsky@fordham.edu

Education and Training

B.S., Novosibirsk State University, Russia, 1980, Biology
Ph.D., Institute of Cytology and Genetics, Novosibirsk, Russia, 1988, Genetics
Postdoctoral fellow, Institute of Genetics and Molecular and Cellular Biology, Strasbourg, France, 1991-1995
Research Associate, Research Assistant Professor, Department of Biology, Dartmouth College, Hanover, NH, 1996-2005

Research Interests

Molecular and Developmental Genetics of Drosophila

Timing of cell proliferation, differentiation and apoptosis is critical for coordinated development of multi-cellular organisms. Metazoans establish developmental timing by utilizing the hormonal regulatory network. Hormones trigger cascades of gene activity in target tissues throughout the organism. With the aim to understand the way in which higher eukaryotes organize stage- and tissue-specific responses to hormonal signals, we work on the hormonal control of Drosophila development. Two hormones coordinately orchestrate the stereotyped program of insect growth and development. Ecdysone is responsible for initiating each developmental transition and Juvenile Hormone (JH) is critical for determining the nature of the transition.

JH is the most versatile insect hormone; it coordinates multiple developmental and physiological processes ranging from molting to aging. Although discovered over 70 years ago, the mechanism of JH action remains unknown. Moreover, despite long-standing efforts and interest, the search for a JH receptor has not been successful. The overall goal of research in the lab is to uncover the molecular mechanism underlying JH action. There are two different projects currently underway in our lab – both of them use the fruitfly Drosophila melanogaster and insect cultured cells, and both involve the combination of molecular genetics and cell biology approaches.

Previously, we identified a group of genes whose expression is induced by JH in Drosophila cultured cells. One of those genes – E75A – encodes the nuclear hormone receptor. E75A is the first known transcription factor that is induced directly by JH. Importantly, we found that JH regulation of E75 gene expression is conserved in mosquito, Anopheles gambiae, and moth, Manduca sexta, suggesting that the function of the E75 gene in JH signaling may be conserved as well. Our first project is on the hormonal control of E75 gene expression. We are working to identify cis-acting regulatory element(s) that confer JH-dependent transcriptional activation of E75. The Drosophila E75A promoter is a direct JH target: (i) it can be activated in the absence of protein synthesis; (ii) it is extremely sensitive to low levels of JH; and (iii) its activation is rapid and shows a decent fold of induction. The additional strength of this project is the use of comparative genomics, approved by our observation that E75 JH-responsiveness is conserved in evolutionary distant species of Diptera and Lepidoptera.

Our second project addresses the biological function of another JH-inducible gene, which is a Drosophila homolog of human ELAC2. ELAC2 is the prostate cancer susceptibility gene. We have found that: (i) Drosophila ELAC2 is an essential gene; (ii) the ELAC2 protein is a part of the tRNA maturation pathway; (iii) ELAC2 has an additional role besides tRNA processing, perhaps involving the cell cycle regulation. Presently, we are using genetic, biochemical, and molecular techniques to understand the role of ELAC2 during development of complex organisms.

Selected Publications

Bernardo, T.J., and Dubrovsky E.B. (2012). The Drosophila juvenile hormone receptor candidates Methoprene-tolerant (MET) and Germ cell-expressed (GCE) utilize a conserved LIxxL motif to bind the FTZ-F1 nuclear receptor. J. Biol. Chem. 287, 7821-7833.

Bernardo, T.J., and Dubrovsky E.B. (2012). Molecular mechanisms of transcription activation by juvenile hormone: A critical role for bHLH-PAS and nuclear receptor proteins. Insects 3, 324-338; doi:10.3390/insects3010324

Xie, X., Dubrovskaya, V.A., and Dubrovsky, E.B. (2011). RNAi knockdown of dRNaseZ, the Drosophila homolog of ELAC2, impairs growth of mitotic and endoreplicating tissues. Insect Biochem. Mol. Biol. 41, 167-177.

Dubrovsky, E.B., Dubrovskaya, V.A., Bernardo, T., Otte, V., DiFilippo, R., and Bryan, H. (2011). The Drosophila FTZ-F1 nuclear receptor mediates juvenile hormone activation of E75A gene expression through an intracellular pathway. J. Biol. Chem. 286, 33689-33700.

Bernardo, T.J., Dubrovskaya, V.A., Jannat, H., Maughan, B., and Dubrovsky E.B. (2009). Hormonal regulation of the E75 gene in Drosophila: identifying functional regulatory elements through computational and biological analysis. J. Mol. Biol. 387, 794-808.

Otte, V., Maughan, B., Hartwig, T., Matta, K., Ross, J., DiFilippo, R., and Dubrovsky, E.B. (2009). A genetic analysis of the cytological region 46F-47B containing the Drosophila melanogaster homolog of the ELAC2 PCA susceptibility gene. DIS 92, 63-69.

Dubrovsky, E.B. (2005). Hormonal cross talk in insect development. Trends Endocrinol. Metab. 16, 6-11.

Berger, E.M., and Dubrovsky, E.B. (2005). Juvenile hormone molecular actions and interactions during development of Drosophila melanogaster. In Vitamins and Hormones (Litwack, G., ed), vol. 73, pp. 175-215, Academic Press, London, UK.

Berger, E.M., Dubrovsky, E.B., Appleby, L., and Dubrovskaya, V.A. (2005). Inhibition of microRNA-induced RNA silencing by 2’-O-methyl oligonucleotides in Drosophila S2 cells. In Vitro Cell. Dev. Biol. 41, 12-18.

Dubrovskaya, V.A., Berger, E.M., Dubrovsky, E.B. (2004). Juvenile hormone regulation of the E75 nuclear receptor is conserved in Diptera and Lepidoptera. Gene 340, 171-177.

Dubrovsky, E.B., Dubrovskaya, V.A., Berger, E.M. (2004). Hormonal regulation and functional role of Drosophila E75A orphan nuclear receptor in the juvenile hormone signaling pathway. Dev. Biol. 268, 258-270.

Dubrovsky, E.B., Dubrovskaya, V.A., Levinger, L., Schiffer, S., Marchfelder, A. (2004). Drosophila RNase Z processes mitochondrial and nuclear pre-tRNA 3’ ends in vivo. Nucleic Acids Res. 32, 255-262.

Sempere, L.F., Sokol, N.S., Dubrovsky, E.B., Berger, E.M., Ambros, V. (2003). Temporal regulation of microRNA expression in Drosophila melanogaster mediated by hormonal signals and Broad-Complex gene activity. Dev. Biol. 259, 9-18.

Dubrovsky, E.B. (2002). Juvenile hormone regulated gene expression in Drosophila melanogaster. In Recent Research Developments in Molecular and Cellular Biology (Pandalai, S.G., ed.), pp. 527-547, Research Signpost, Trivandrum, India.

Dubrovsky, E.B., Dubrovskaya, V.A., Berger, E.M. (2002). Juvenile hormone signaling during oogenesis in Drosophila. Insect Biochem. Mol. Biol. 32, 1555-1565.

Sempere, L.F., Dubrovsky, E.B., Dubrovskaya, V.A., Berger, E.M., and Ambros, V. (2002). The expression of the let-7 small regulatory RNA is controlled by ecdysone during metamorphosis in Drosophila melanogaster. Dev. Biol. 244, 170-179.

Dubrovsky, E.B., Dubrovskaya, V.A., and Berger, E.M. (2001). Selective binding of Drosophila BR-C isoforms to a distal regulatory element in the hsp23 promoter. Insect Biochem. Mol. Biol. 31, 1231-1239.

Dubrovsky, E.B., Dubrovskaya, V.A., Bilderback, A.L., and Berger, E.M. (2000). The isolation of two juvenile hormone-inducible genes in Drosophila melanogaster. Dev. Biol. 224, 486-495.