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Developmental and Molecular Genetics My laboratory is interested in understanding the molecular mechanisms of growth control. Our primary focus is on the transforming growth factor-β-like pathways (TGFβ) and microRNAs. TGFβ signaling pathways. TGFβ growth factors are expressed in most tissues of animals (from sponges to humans) and are involved in regulating cellular growth, patterning, and cell fate. Mutations in various signaling components of these pathways are associated with several important diseases and cancers. Because of the powerful experimental techniques available in Drosophila and C. elegans, and that fact that these pathways are conserved between invertebrates and mammals, we are using flies and nematodes as model systems to dissect this signal transduction pathway. In both organisms, we have executed genetic screens to identify new aspects of TGFβ signaling and, as a complement to our genetic studies, we have generated microarray data in both organisms to identify downstream targets of these pathways as an aid to understand how they regulate growth. Using RNAi and genetic techniques, we are dissecting the function of these genes to determine how they interface with TGFβ signaling. microRNAs in developmental pathways. microRNAs are small RNAs (~21-23 nucleotides) that regulate gene expression by attenuating the translation of mRNAs in animal cells. They have been implicated in a variety of cellular responses, including the control of cell fate. We are interested in determining what cellular processes they control and what genes they target for translational repression. We have developed a microarray platform to assay their expression (in collaboration with R. Hart), and have developed algorithms to predict their targets (in collaboration with H. Robins). These tools are being applied to 1) a series of cancers (in collaboration with M. Reiss) and 2) a variety of cellular differentiation events to determine how the expression of microRNAs changes as cell fates change. Ibáñez-Ventoso, C., M. Yang, S. Guo, H. Robins, R.W. Padgett, and M. Padgett, R.W. and G.I. Patterson (2006) C. elegans TGFβ Signaling Pathways, Patterson, G.I. and R.W. Patterson (2006) TGFb Signaling in C. elegans, Eds. Goff, L.A., M. Yang, J. Bowers, R. C. Getts, R. W. Padgett, R. P. Hart (2005). Rational probe optimization and enhanced detection strategy for microRNAs using microarrays, RNA Biology, in press. Kirilly, D., E.P. Spana, N. Perrimon, R.W. Padgett and T. Xie (2005). BMP Maduzia, L.L., A.F. Roberts, H. Wang, X. Lin, L.J. Chen, C.M. Zimmerman, S. Cohen, X-H. Feng, and R.W. Padgett (2005). C. elegans serine/threonine kinase KIN-29 modulates,TGFβ signaling and regulates body size formation, BMC: Dev Biol. 5:8. Patton, J.R., and R. W. Padgett (2005). Pseudouridine modification in Yang, M., Y. Li, and R.W. Padgett (2005) MicroRNAs: Small regulators with a big impact, Cyto. and Growth Factor Reviews, in press. Yu, B., Z. Yang, J. Li, S. Minakhina, M.Wang, R.W. Padgett, R. Steward, and X. Chen (2005). Methlyation as Crucial Step in Plant microRNA Biogenesis, Science 307:932-935. Yang, M., Y. Funakoshi, and R.W. Padgett (2004). Genome-wide Microarray Analysis of TGFβ Signaling in the Drosophila Brain, BMC Dev Biol, 4:14. Patton, J.R. and R.W. Padgett (2003). Caenorhabditis elegans pseudouridine synthase activity in vivo: tRNA is a substrate but not U2 small nuclear RNA, Biochem. Journal 372(Pt 2):595-602. Gumienny, T.L. and R.W. Padgett (2003) A small issue addressed, BioEssays 25:305-308. Nelson, D. and R.W. Padgett (2003) Insulin worms its way into the spotlight, Genes & Dev 17:813-818. Savage-Dunn, C., L.M. Maduzia, C.M. Zimmerman, A.F. Roberts, S. Cohen, R. Tokarz, and R.W. Padgett (2003) A genetic screen for body size mutant in C. elegans reveals many TGFβ pathway components, Genesis 35:239-247. Maduzia, L.L., T.L. Gumienny, C.M. Zimmerman, H. Wang, P. Shetgiri, S. Krishna, A.F. Roberts, and R.W. Padgett (2002). lon-1 regulates Caenorhabditis elegans body size downstream of the dbl-1 TGFβ-like signaling pathway, Dev. Biol. 246:418-428. Gumienny, T.L. and R.W. Padgett (2002) The other side of TGFβ superfamily signal regulation: thinking outside the cell. Trends in Endocrinology 13:295-299. Padgett, R.W., and Patterson, G.I. (2001) New developments for TGFβ, Dev. Cell 1:343-349. Savage-Dunn, C., Tokarz, R., Wang, H., Cohen, S., Giannikas, C. and Padgett, R.W. (2000) sma-3 Smad has specific and critical functions in DBL-1/SMA-6 TGFβ -like signaling. Dev. Biol. 223:70-76. Patterson, G. I. and Padgett, R.W. (2000) TGFβ-related Pathways: Roles in C. elegans development, Trends in Genetics 16:27-33. Zimmerman, C. and Padgett, R.W. (2000) TGFb Signaling mediators and modulators, Gene 249:17-30. Suzuki, Y., M.D. Yandell, P.J. Roy, M. Fleischmann, S. Krishna, C. Savage-Dunn, R.M. Ross, F. Mueller, R.W. Padgett, and W.B. Wood. (1999). A C. elegans BMP2,4 homolog determines body size and contributes to male tail patterning Development, 126: 241-250. Krishna, S. L.M. Maduzia, and R.W. Padgett. (1999). Specificity of TGFβ signaling is imparted by distinct type I receptors and their associated SMAD proteins, Development 126: 251-260. Das, P., H. Inoue, J.C. Baker, H. Beppu, M. Kawabata, R.M. Harland, K. Miyazono, and R.W. Padgett. (1999). Drosophila dSmad2 and Atr-I transmit activin/TGFβ Signals, Genes to Cells 4: 123-134. Coavita, A., Krishna, S., Zheng, H., Padgett, R.W.and Colotti, J.G. (1998). Pioneer axon guidance by UNC-129, a C. elegans TGF-β, Science 281: 706-709. Das, P., Maduzia, L., Wang, H., Finelli, A., Cho, S-H., Smith, M. and Padgett, R.W. (1998). The Drosophila gene Medea reveals the requirement for different classes of Smads in dpp signaling, Development 125: 1519-1528. Padgett, R.W., P. Das, and S. Krishna (1998). TGFβ signaling, Smads, and tumor suppressors. BioEssays, 20:382-390. Padgett, R.W., S-H. Cho, and C. Evangelista (1998). Smads are the central component in TGFβ signaling, Pharmacology and Therapeutics 78: 47-52. Maduzia, L., and R. W. Padgett, (1997). Drosophila Mad, a member of the Smad family, translocates to the nucleus upon stimulation of the dpp pathway. Biochem. Biophys. Res. Comm. 238:595-598. Newfeld, S.J., R. W. Padgett, S. D. Findley, B. G. Richter, M. de Cuevas, and W. M. Gelbart (1997). Molecular evolution at the decapentaplegic locus in Drosophila, Genetics 145:297-309.
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Research
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