dc.creator | Sturgill, Emma Gray | |
dc.date.accessioned | 2020-08-23T15:52:39Z | |
dc.date.available | 2015-11-26 | |
dc.date.issued | 2014-11-26 | |
dc.identifier.uri | https://etd.library.vanderbilt.edu/etd-11242014-142447 | |
dc.identifier.uri | http://hdl.handle.net/1803/14780 | |
dc.description.abstract | Mitotic kinesins represent the new age targets of spindle-poisoning chemotherapies. The kinesin-5 Eg5 is one such example, as kinesin-5 inhibitors (K5Is) induce a lethal mitotic arrest from failed spindle assembly. Documented here is the discovery of a novel spindle assembly pathway that confers K5I-resistance to human tumor cells in culture. This “reverse-jackknifing” pathway is mechanically distinct from the canonical Eg5-driven mechanism, relying instead on the activity of the kinesin-12 Kif15. The work shown here details the molecular function and biochemical properties of Kif15, while also providing insight into the larger question of why anti-mitotic pharmacological agents fail as chemotherapies. Future efforts will evaluate the combination of K5Is with Kif15-inhibitors as a novel strategy for the treatment of neoplasias. Ultimately, this study bridges mitotic mechanisms with clinically relevant problems, being of interest to cell biologists, cancer biologists, and clinicians. | |
dc.format.mimetype | application/pdf | |
dc.subject | cancer | |
dc.subject | chemotherapy | |
dc.subject | kinesin | |
dc.subject | microtubule | |
dc.subject | mitosis | |
dc.subject | spindle | |
dc.title | A Reductionist Study into the Physiology, Pathology, and Pharmacology of the Mitotic Spindle | |
dc.type | dissertation | |
dc.contributor.committeeMember | Irina Kaverina | |
dc.contributor.committeeMember | Ethan lee | |
dc.contributor.committeeMember | Alissa Weaver | |
dc.type.material | text | |
thesis.degree.name | PHD | |
thesis.degree.level | dissertation | |
thesis.degree.discipline | Cell and Developmental Biology | |
thesis.degree.grantor | Vanderbilt University | |
local.embargo.terms | 2015-11-26 | |
local.embargo.lift | 2015-11-26 | |
dc.contributor.committeeChair | Matthew Tyska | |