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Title page for ETD etd-11242014-142447


Type of Document Dissertation
Author Sturgill, Emma Gray
URN etd-11242014-142447
Title A Reductionist Study into the Physiology, Pathology, and Pharmacology of the Mitotic Spindle
Degree PhD
Department Cell and Developmental Biology
Advisory Committee
Advisor Name Title
Matthew Tyska Committee Chair
Alissa Weaver Committee Member
Ethan lee Committee Member
Irina Kaverina Committee Member
Keywords
  • cancer
  • chemotherapy
  • kinesin
  • microtubule
  • mitosis
  • spindle
Date of Defense 2014-11-21
Availability unrestricted
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.
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