Rich, Kayla
Kayla is in the Biochemistry, Molecular and Structural Biology Graduate Program, and joined the CMB Training Program in 2022.
Mentor: Dr. Jorge Torres
Cancer progression often involves transitions between a high cell proliferation rate to a high migratory rate then back again. These transitions are known as the epithelial-to-mesenchymal (EMT) and mesenchymal-to-epithelial (MET) transitions. EMT and MET are characterized by cytoskeletal reorganizations, changes in cell-cell contacts, and changes in cellular apical-basal polarity. The importance of the cytoskeletal network in these transitions, however, remains understudied. The microtubule network is a major cytoskeletal component that is necessary for cell migration, proliferation, polarity, and intracellular trafficking. Microtubule structures undergo dynamic rearrangements throughout the cell cycle in part due to the katanin microtubule-severing enzyme family. The roles of the katanins within EMT and MET have yet to be determined, but they are known to interact with and have their activity regulated by DYRK2 and LAPSER1, both of which regulate cell cycle progression and are also involved in EMT signaling. I hypothesize that katanin microtubule-severing activity and its regulation by DYRK2 and LASPER1 are important for the EMT and MET transitions. To test this, I will determine the effect of modulating katanin protein levels on EMT and MET using katanin CRISPR iCas9 inducible knockout and overexpression cell lines in conjunction with cell proliferation, migration, and invasion assays. I will also perform proteomic analyses of katanins in EMT and MET, which will provide invaluable details on key katanin interactions, protein levels, and modifications in EMT and MET. I will further validate the mechanisms of katanin regulation through depletion-add back rescue assays, DYRK2 inhibitor treatment, and microtubule-severing-assays. Together, these aims will determine the role of the katanins in EMT and MET, and the importance of regulating katanin protein levels, activity, localization, and posttranslational modifications for EMT and MET transitions.
