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Scientific Contributions
Demonstrated localized supercoiling occurs in Eukaryotic cells.
As as graduate student at Harvard University I sequenced the first eukaryotic Topoisomerase II, yeast TOP2, and showed its partial homology to prokaryotic DNA gyrases. While it had been surmised that localized supercoiling of DNA may be generated within the nucleus due to the necessity of rapidly unwinding the DNA during such fundamental processes as replication and transcription, it had never been tested, as no experimental methodology was available. By expressing bacterial E. coli gyrase in the yeast S. cerevisiae which relaxes only negatively supercoiled DNA, I demonstrated that localized supercoiling does indeed exist by observing net positively supercoiled plasmid DNA.
Supercoiling of intracellular DNA can occur in eukaryotic cells. Giaever GN, Wang JC. Cell 1988;55(5):849-56. Times cited: 225.
Discovery of drug-induced haploinsufficiency
Drug-induced haploinsufficiency is an increased drug sensitivity phenotype observed in a heterozygous cell deleted for one copy of the drug’s target. Exploiting this phenotype, I developed a genome-wide assay that allows a small molecule or drug target to be identified in an agnostic manner.
Genomic profiling of drug sensitivities via induced haploinsufficiency. Giaever G, Shoemaker DD, Jones TW, Liang H, Winzeler EA, Astromoff A, Davis RW. Nature genetics. 1999;21(3):278-83. Times Cited: 375. Subject of News \& Views; Nature Genetics. Oliver S. Redundancy reveals drugs in action. Nature genetics. 1999;21(3):245-6.
Work with the Yeast Knockout Consortium
I played a significant role in the community-driven Yeast Knockout Project to construct the first systematic deletion collection in any organism, led and made feasible only by the technology developed at the Stanford Genome Technology Center team.
Functional profiling of the Saccharomyces cerevisiae genome. Giaever G, Chu AM, Ni L et al. Nature. 2002;418(6896):387-391. Times cited: 2601.