Michael R Cancilla

Publications (2)40.17 Total impact

• Source

  Available from: psu.edu

  Article: Chemical genetics identifies Rab geranylgeranyl transferase as an apoptotic target of farnesyl transferase inhibitors.

  Mark R Lackner, Rachel M Kindt, Pamela M Carroll, Katherine Brown, Michael R Cancilla, Changyou Chen, Heshani de Silva, Yvonne Franke, Bo Guan, Tim Heuer, [......], Dianne Parry, Juan J Perez-Villar, Rajashekar K Reddy, Hong Xiao, Hangjun Zhan, Mark Cockett, Greg Plowman, Kevin Fitzgerald, Michael Costa, Petra Ross-Macdonald
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  ABSTRACT: A chemical genetics approach identified a cellular target of several proapoptotic farnesyl transferase inhibitors (FTIs). Treatment with these FTIs caused p53-independent apoptosis in Caenorhabditis elegans, which was mimicked by knockdown of endosomal trafficking proteins, including Rab5, Rab7, the HOPS complex, and notably the enzyme Rab geranylgeranyl transferase (RabGGT). These FTIs were found to inhibit mammalian RabGGT with potencies that correlated with their proapoptotic activity. Knockdown of RabGGT induced apoptosis in mammalian cancer cell lines, and both RabGGT subunits were overexpressed in several tumor tissues. These findings validate RabGGT, and by extension endosomal function, as a therapeutically relevant target for modulation of apoptosis, and enhance our understanding of the mechanism of action of FTIs.
  Cancer Cell 05/2005; 7(4):325-36. · 26.57 Impact Factor
• Article: High-throughput gene mapping in Caenorhabditis elegans.

  Kathryn A Swan, Damian E Curtis, Kathleen B McKusick, Alexander V Voinov, Felipa A Mapa, Michael R Cancilla
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  ABSTRACT: Positional cloning of mutations in model genetic systems is a powerful method for the identification of targets of medical and agricultural importance. To facilitate the high-throughput mapping of mutations in Caenorhabditis elegans, we have identified a further 9602 putative new single nucleotide polymorphisms (SNPs) between two C. elegans strains, Bristol N2 and the Hawaiian mapping strain CB4856, by sequencing inserts from a CB4856 genomic DNA library and using an informatics pipeline to compare sequences with the canonical N2 genomic sequence. When combined with data from other laboratories, our marker set of 17,189 SNPs provides even coverage of the complete worm genome. To date, we have confirmed >1099 evenly spaced SNPs (one every 91 +/- 56 kb) across the six chromosomes and validated the utility of our SNP marker set and new fluorescence polarization-based genotyping methods for systematic and high-throughput identification of genes in C. elegans by cloning several proprietary genes. We illustrate our approach by recombination mapping and confirmation of the mutation in the cloned gene, dpy-18.
  Genome Research 07/2002; 12(7):1100-5. · 13.61 Impact Factor