Scott G. Kennedy

Assistant Professor
Department of Pharmacology

sgkennedy@wisc.edu

Trainer in the Following Programs:

  • Molecular and Cellular Pharmacology
  • Genetics
  • Cell and Molecular Biology

Honors and Awards:

  • 2007-2011 - Shaw Scientist Award
  • 2006-2010 - Pew Scholar Award
  • 2005-2007 - Medical Education and Research Committee Award
  • 2001-2004 - National Research Science Award

Small RNAs and RNAi

Small RNAs of 21-24 nucleotides in length function in a remarkably wide range of biological processes, including gene silencing, translational regulation, heterochromatin formation, developmental timing, antiviral defense, and genome rearrangement. The long-term interest of my laboratory is to gain a molecular understanding of the endogenous biological functions of small RNAs. In particular, we are interested in the evolutionarily conserved process of RNA interference (RNAi). Exposure of many organisms to double-stranded (ds) RNA causes the degradation of mRNA molecules containing sequences homologous to the trigger dsRNA. dsRNAs are processed by the RNase III enzyme Dicer (DCR-1) into small RNAs [termed small interfering RNAs (siRNAs)] which hybridize to and induce the degradation of cognate mRNAs. This gene-silencing phenomenon has been termed RNA interference (RNAi).

We are undertaking genetic screens in the model organism C. elegans to identify and characterize the RNAi machinery. These screens are targeting genes that are required for appropriate organismal responses to dsRNA and genes which function to negatively regulate RNAi. An additional goal of the laboratory is to further our understanding of the endogenous biological functions of this conserved RNAi machinery. We are using genetics, molecular biology, and biochemistry to answer these questions.

Much of the RNAi machinery is conserved in mammals, indicating that research on RNAi in model organisms such as C. elegans will not only be fundamental to our understanding of the biology of RNAi, but also instrumental in the rational use of RNAi technology as a possible therapeutic to treat human disease.

Selected Publications: Articles on PubMed
  • Duchaine T, Wohlschlegel J, Kennedy S, Bei Y, Conte D, Pang K, Brownell D, Harding S, Mitani S, Ruvkun G, Yates J, Mello C. (2006). Functional Proteomics Reveals the Biochemical Niche of C. elegans DCR-1 in Multiple small-RNA-mediated Pathways. Cell. 124:343-354.

  • Wang D, Kennedy S, Conte D Jr, Kim JK, Gabel HW, Kamath RS, Mello CC, and Ruvkun G. (2005). Somatic misexpression of germline P granules and enhanced RNA interference in retinoblastoma pathway mutants. Nature. 436:593-597. PDF PMID 16049496

  • Sieburth D, Ch'ng Q, Dybbs M, Tavazoie M, Kennedy S, Wang D, Dupuy D, Rual JF, Hill DE, Vidal M, Ruvkun G, and Kaplan JM. (2005). Systematic analysis of genes required for synapse structure and function. Nature. 436:510-517. PDF PMID 16049479

  • Kim JK, Gabel HW, Kamath RS, Tewari M, Pasquinelli A, Rual JF, Kennedy S, Dybbs M, Bertin N, Kaplan JM, Vidal M, and Ruvkun G. (2005). Functional genomic analysis of RNA interference in C. elegans. Science. 308:1164-1167. PDF PMID 15790806

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