My lab is interested in the mechanisms by which cells divide their genetic material to the two daughter cells. We want to understand how cells assemble the mitotic spindle, how the cell aligns and then accurately segregates its chromosomes, and how these processes are regulated during mitosis. The accurate segregation of chromosomes is critical during development to avoid chromosomal abnormalities such as those associated with Downs Syndrome, and chromosome segregation gone awry is a hallmark of cancer.
Of prime importance during spindle assembly are the regulated dynamics of microtubules that occur during interphase and mitosis and how the dynamics of different populations of microtubules are both temporally and spatially regulated. We use a combination of in vitro assays for the regulation of microtubule dynamics with purified proteins, reconstitution of spindle formation using meiotic extracts from Xenopus eggs, and high-resolution live and fixed cell imaging of microtubule dynamics and organization in living cells in culture. This approach provides a framework to further decipher the molecular mechanism of spindle assembly and chromosome segregation. We ask questions regarding the multiple physiological roles of microtubules in cells, how their dynamics are regulated by cellular proteins, and how the activity of microtubule dynamics regulators are controlled temporally and spatially within cells. Our ultimate goals are to identify new molecular targets that can be used to treat a variety of diseases in which altered microtubule activity is critical and to develop drugs that can target these regulators.
Affiliations
- Professor of Biochemistry and Molecular Biology
- Adjunct Professor of Anatomy and Cell Biology
- Adjunct Professor of Biology
- Member, Interdisciplinary Biochemistry Graduate Program
Awards and Honors
- American Cancer Society Research Scholar (2003)
- Women in Cell Biology Junior Career Recognition Award from American Society for Cell Biology (2003)
- Leukemia and Lymphoma Scholar Award (2001)
Publications
Articles
- Stout, J.R., Rizk, R. and Walczak, C.E. (2009). Protein Inhibition by Microinjection and RNA-mediated Interface in Tissue Culture Cells: Complimentary Approaches to Study Protein Function. Methods in Mol. Biol. 518:1-21.
- Rizk, R., Bohannon, K., Wetzel, L., Powers, J.A., Shaw, S.L., and Walczak, C.E. (2009). MCAK and Paclitaxel Have Differential Effects on Spindlee Organization and Microtubule Dynamics. Mol. Biol. Cell. E-pub ahead of print. PMID: 19158381.
- Cai, S. and Walczak, C.E. (2008). Kinetochore Attachment: How the Hec can a cell do it? Curr. Biol. 18: R1093-1096.
- Walczak, C.E. and Heald, R.E. (2008). Mechanisms of Spindle Assembly and Chromosome Segregation. Int. Rev. Cytology 265: 111-158. PMID: 18275887.
- Cai, S., Weaver, L., Ems-McClung, S.C., and Walczak, C.E. (2008). Kinesin-14 Family Proteins HSET/XCTK2 Control Spindle Morphology by Cross-Linking and Sliding Microtubules. Mol. Biol. Cell. E-pub ahead of print. PMID: 19116309.
- Zhang, X., Ems-McClung, S.C., and Walczak, C.E. (2008). Aurora A Phosphorylates MCAK to Control Ran-dependent Spindle Bipolarity. Mol. Biol. Cell. 19: 2752-2765. PMID: 18434591.
- Shaw SL, Walczak C.E. (2007). Spindles: One Speckle at a Time. Nat. Cell Biol. 9:1223-1224. PMID: 17975545.
- Zhang, X., Lan, W., Ems-McClung, S.C., Stukenberg, P.T., and Walczak, C.E. (2007). Aurora B Phosphorylates Multiple Sites on Mitotic Centromere-Associated Kinesin to Spatially and Temporally Regulate its Function. Mol. Biol. Cell. 18: 3264-3276. PMID: 17567953.
- Ems-McClung, S.C., Hertzer, K.M., Zhang, X., Miller, M., and Walczak, C.E. (2007). The Interplay of the N- and C-terminal Domains of MCAK Control Microtubule Depolymerization Activity and Spindle Assembly. Mol. Biol. Cell. 18: 282-294. PMID: 17093055.
|