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) in C. elegans and Drosophila.
TGFβ signaling pathways.
Members of the TGFβ growth factor family are conserved in all animal phyla (from sponges to humans) and are expressed in essentially all vertebrate tissues, where they are involved in regulating cellular growth, patterning, and cell fate. As expected from their potent growth-regulatory properties, mutations in signaling components of these pathways are often associated with several diseases and cancers. Because of the powerful experimental techniques available in C. elegans and Drosophila, and that fact that these pathways are conserved, we are using nematodes and flies 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 screens, we have generated microarray data in both organisms to identify downstream targets of these pathways as an aid to understand how they regulate growth.
Trafficking and Regulation of TGFβ pathways.
Mutations from our genetic screens have identified a number of essential signaling components for TGFβ. These include the ligand, the two receptors, the Smads, and schnurri, which is a downstream transcription factor. In addition, we have identified a conserved co-receptor, which intersects with the trafficking of TGFβ. Another gene from our screen appears to be involved with degradation/trafficking of the receptors. Recent evidence suggests that signaling pathway strength is intimately associated with endocytosis, and these two genes from our screen offer new avenues to explore the trafficking, signaling, and degradation of the TGFβ pathway in C. elegans and Drosophila.
Development of a co-CRISPR technique in Drosophila
Genome editing using CRISPR has become a valuable tool in research, but identifying modifications can be time consuming and labor intensive. We developed a co-CRISPR strategy in Drosophila to simultaneously target a gene of interest and a marker gene, ebony, which is a recessive gene that produces dark body color. We found that Drosophilabroods containing higher numbers of CRISPR-induced ebony mutations (“jackpot” lines) are significantly enriched for indel events in a separate gene of interest, while broods with few or no ebony offspring showed few mutations in the gene of interest. This co-CRISPR technique significantly improves the screening efficiency in identification of genome editing events in Drosophila.
microRNAs in developmental pathways.
microRNAs are small RNAs (~21-23 nucleotides) that regulate gene expression by attenuating the translation of mRNAs in animal cells. We have shown that bantam, a conserved microRNA, regulates TGFβ signaling in Drosophila, and that TGFβ signaling induces the expression of bantam, thereby forming a regulatory loop. Current studies focus on understanding how bantam regulates TGFβ in the wing and the brain.
190 Frelinghuysen Road
Piscataway, NJ 08854
Complete list of publications: [Pubmed]
TGFb Signaling in C. elegans
Patterson, G.I. and R.W. Patterson (2008) TGFb Signaling in C. elegans, Eds. C. Heldin and P. ten Dijke, Springer Science.
TGFb Family Signaling in the Nematode
Padgett, R.W. and G.I. Patterson (2008) TGFb Family Signaling in the Nematode, C. elegans, pp. 527-545, Eds. R. Derynck and K. Miyazono, The TGFb Family, Cold Spring Harbor Press.
TGFb superfamily signaling: notes from the desert
Padgett, R.W. and M. Reiss (2007) TGFb superfamily signaling: notes from the desert, Development 134:3565-3569.
MicroRNAs: Small regulators with a big impact
Yang, M., Y. Li, and R.W. Padgett (2005) MicroRNAs: Small regulators with a big impact, Cyto. and Growth Factor Reviews, 16:4-5:387-393.
Insulin worms its way into the spotlight
Nelson, D. and R.W. Padgett (2003) Insulin worms its way into the spotlight, Genes & Dev 17:813-818.
A small issue addressed
Gumienny, T.L. and R.W. Padgett (2003) A small issue addressed, BioEssays 25:305-308.
The other side of TGFb superfamily signal regulation: thinking outside the cell
Gumienny, T.L. and R.W. Padgett (2002) The other side of TGFb superfamily signal regulation: thinking outside the cell, Trends in Endocrinology 13:295-299.
New Developments for TGFb
Padgett, R.W., and G.I. Patterson (2001) New Developments for TGFb, Dev. Cell 1:343-349.
TGFb Signaling Mediators and Modulators
Zimmerman, C. and R.W. Padgett (2000) TGFb Signaling Mediators and Modulators, Gene 249:17-30.
TGFb-related Pathways: Roles in C. elegans Development
Patterson, G. I. and R.W. Padgett (2000) TGFb-related Pathways: Roles in C. elegans Development, Trends in Genetics 16:27-33.
Genetic Approaches to TGFb Signaling Pathways
Das, P., L.L. Maduzia, and R. W. Padgett (1999) Genetic Approaches to TGFb Signaling Pathways, Cyto. and Growth Factor Reviews 10:179-186.
TGFb Signaling Pathways and Human Diseases
Padgett, R. W. (1999) TGFb Signaling Pathways and Human Diseases, Cancer & Metastasis Reviews 18:247-259.
Intracellular Signaling: Fleshing out the TGFb pathway
Padgett, R.W. (1999) Intracellular Signaling: Fleshing out the TGFb pathway, Current Biology 9:R408-R411.
Smads are the Central Component in TGFb Signaling
Padgett, R.W., S-H. Cho, and C. Evangelista (1998). Smads are the Central Component in TGFb Signaling, Pharmacology and Therapeutics 78: 47-52.
TGFb Signaling, Smads, and Tumor Suppressors
Padgett, R.W., P. Das, and S. Krishna (1998). TGFb Signaling, Smads, and Tumor Suppressors, BioEssays 20:382-390.
The tolloid-like Genes in Invertebrates, In: The Astacins-Structure and Function of a New Protein Family
Padgett, R.W., A.L. Finelli, C. Savage, T. Xie, and S.-H. Cho (1997). The tolloid-like Genes in Invertebrates, In: The Astacins-Structure and Function of a New Protein Family, R. Zwilling and W. Stocker, eds., Verlag DR. Kovac, Hamburg, Germany.
Genetic and Biochemical Analysis of TGFb Signal Transduction
Padgett, R.W., C. Savage, and P. Das (1997). Genetic and Biochemical Analysis of TGFb Signal Transduction, Cyto. and Growth Factor Reviews 8: 1-9.
Nomenclature: Vertebrate Mediators of TGFb Family Signals
Derynck, R., W.M. Gelbart, R.M. Harland, C.-H. Heldin, S.E. Kern, J. Massagué, D.A. Melton, M. Mlodzik, R.W. Padgett, A.B. Roberts, J. Smith, G.H. Thomsen, B. Vogelstein, and X.-F. Wang (1996). Nomenclature: Vertebrate Mediators of TGFb Family Signals, Cell 87:1996.
The Fly According to Lawrence
Padgett, R.W. (1993). The Fly According to Lawrence. BioScience 43:251-252.
The L1 Family in Mice. In Developmental Control of Globin Gene Expression
Edgell, M.H., S.C. Hardies, D.D. Loeb, W.R. Shehee, R.W. Padgett, F.H. Burton, M.B. Comer, N.C. Casavant, F.D. Funk and C.A. Hutchison III (1987). The L1 Family in Mice. In Developmental Control of Globin Gene Expression, Alan R. Liss, Inc., pp. 107-129.
"b Homologous Structures in the b Globin Locus of the Mouse"
Hutchison III, C.A., B.A. Brown, M.G. Davis, S.C. Hardies, A. Hill, R.W. Padgett, S.J. Phillips, B.E.L. Timmons IV, S.G. Weaver and M.H. Edgell (1983). "b Homologous Structures in the b Globin Locus of the Mouse". In Regulation of Hemoglobin Biosysnthesis. (Eugene Goldwasser, ed.) Elsevier Biomedical, New York, 51-68.
"The Mouse Beta Hemoglobin Locus"
Edgell, M.H., S. Weaver, C.L. Jahn, R.W. Padgett, S.J. Phillips, C.F. Voliva, M.B. Comer, S.C. Hardies, N.L. Haigwood, C.H. Langley, R.R. Racine and C.A. Hutchison III (1981). "The Mouse Beta Hemoglobin Locus". In Organization and Expression of Globin Genes. (G. Stamatoyannpoulos and A.W. Nienhuis, eds.) Alan R. Liss, Inc., New York, 69-88.
Richard W. Padgett, Ph.D., is Professor Emeritus of Department of Molecular Biology and Biochemistry, former Laboratory Director at the Waksman Institute of Microbiology, and former Director of Graduate Programs in Cell and Developmental Biology and Molecular Biology and Biochemistry. He is member of the Cancer Institute and Human Genetics Institute of New Jersey. His research interests focused on understanding the molecular mechanisms of growth control. His lab's primary focus was on transforming growth factor-β-like pathways (TGFβ) in C. elegans and Drosophila. Using nematodes and flies as model systems to dissect the signal transduction pathway. Padgett lab research helped to identify two genes that are involved in regulating the trafficking of the two TGFb receptors and studied the altering effect of the genes on the trafficking of the receptors.