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Karen Oegema

Research

My lab is interested in the interface between cell and cancer biology. My group has had a long-term interest in the molecular machinery underlying mitosis and cytokinesis. This research has revealed that in addition to common themes, there is also significant variation between cell types in how cell division is accomplished. A current focus in the lab is to determine whether these differences can be leveraged to induce death due to aberrant mitosis in a cell type specific fashion as a chemotherapeutic strategy.

An example of this has arisen from our work on centrosomes. Through a combination of experiments in the model system C. elegans and in human cells, we have made important contributions to understanding the pathway that controls centrosome duplication, which depends on a centrally important regulatory kinase called Plk4. To explore the therapeutic potential of centrosome removal in cancer, we collaborated with the Small Molecule Discovery Group in the Ludwig Institute for Cancer Research to develop the first potent, specific, cellularly active Plk4 inhibitor. Our experiments using this inhibitor, which we call centrinone, revealed striking differences in how cells respond to centrosome removal, and have suggested that centrosome removal could have therapeutic potential for specific cancer types. We are currently working to understand the molecular basis of these differential effects and are initiating screens to expand our understanding of variation in the cell division machinery across cell types.

A second research avenue in my lab has been aimed at generating a phenotypic map of the genes essential for embryonic development in a model metazoan. In this project, we are taking a high-content approach based on time-lapse imaging of tissue specification and morphogenesis during embryogenesis to generate a functional gene network for the set of ~2000 C. elegans genes required for embryonic development. To analyze the 26,000 time-lapse movies resulting from this effort, we have developed automated methods for phenotypic parameterization and comparison that allow us to identify genes with similar phenotypes, suggesting that they function in common pathways. Of the genes that we are characterizing in this effort, 75% are conserved in humans and 900 are functionally uncharacterized, suggesting that this approach will allow us to predict function for a large number of human genes.

Select Publications

  • Wang S., Ochoa S.D., Khaliullin R.N., Gerson-Gurwitz A., Hendel J.M., Zhao Z., Biggs R., Chisholm A.D., Desai A., Oegema, K.*, and R.A. Green*. 2019. A high-content imaging approach to profile C. elegans embryonic development. Dev Cell. 2019. 48:864-872. doi: 10.1016/j.devcel.2019.02.002. PMID: 30827898 *Co-corresponding
  • Khaliullin, R., Green, R.A., Shi, L.Z., Berns, M.W., Gomez-Cavazos, J.S., Desai, A. and K. Oegema. 2018. Positive feedback between contractile ring myosin and ring-directed cortical flow drives cytokinesis. Elife. doi: 10.7554/eLife.36073. PMID: 29963981.
  • Lee, K-Y., Green, R.A. Gutierrez, E., Gomez-Cavazos, J.S., Kolotuev, I., Wang, S., Desai, A., Groisman, A., and K. Oegema. 2018. CYK-4 functions independently of its centralspindlin partner ZEN-4 to cellularize oocytes in germline syncytia. Elife. doi: 10.7554/eLife.36919. PMID: 29989548.
  • Meitinger, F., Anzola, J.V., Kaulich, M., Richardson, A., Stender, J.D., Benner, C., Glass, C.K., Dowdy, S.F., Desai, A., Shiau, A.K. and K. Oegema. 2016. 53BP1 and USP28 mediate p53 activation and G1 arrest after centrosome loss or extended mitotic duration. J Cell Bio. 214:155-66. doi: 10.1083/jcb.201604081. PMID: 27432897
  • Wang, S., Wu, D., Quintin, S., Green, R.A., Cheerambathur, D.K., Ochoa, S.D., Desai, A., and K. Oegema. 2015. NOCA-1 Functions with γ-tubulin and in parallel to Patronin to assemble non-centrosomal microtubule arrays in C. elegans. Elife. doi: 10.7554/eLife.08649. PMID: 26371552.
  • Woodruff, J.B., Wueseke, O., Viscardi, V., Mahamid, J., Ochoa, S.D., Bunkenborg, J., Widlund, P.O., Pozniakovsky, A., Zanin, E., Bahmanyar, S., Zinke, A., Hong, S.H., Decker, M., Baumeister, W., Andersen, J.S., Oegema, K.,* and A.A. Hyman*. 2015. Regulated assembly of a supramolecular centrosome scaffold in vitro. Science. 348(6236):808-12. doi: 10.1126/science.aaa3923. PMID: 25977552. *Co-corresponding
  • Wong, Y.L., Anzola, J.V., Davis, R.L., Yoon, M., Motamedi, A., Kroll, A., Seo, C.P., Hsia, J.E., Kim, S.K., Mitchell, J.W., Mitchell, B.J., Desai, A., Gahman, T.C., Shiau, A.K., and K. Oegema. 2015. Reversible centriole depletion with an inhibitor of Polo-like kinase 4. Science>. 348:1155-60. doi: 10.1126/science.aaa5111. PMID: 25931445
  • Zanin, E., Desai, A., Poser, I., Toyoda, Y., Andree, C., Moebius, C., Bickle, M., Conradt, B., Piekny, A., and K. Oegema. 2013. A Conserved RhoGAP limits M-phase contractility and coordinates with microtubule asters to confine RhoA during cytokinesis. Dev Cell. 26:496-510.
  • Lettman, M.M., Wong, Y.L., Viscardi, V., Niessen, S., Chen, S., Shiau, A.K., Zhou, H., Desai, A., and K. Oegema. 2013. Direct binding of SAS-6 to ZYG-1 recruits SAS-6 to the mother centriole for cartwheel assembly. Dev Cell. 25:284-298.
  • Green, R., Kao, H.L., Audhya, A., Arur, S., Mayers, J.R., Fridolfsson, H., Schulman, M., Schloissnig, S., Niessen, S., Laband, K., Wang, S., Starr, D., Hyman, A., Schedl, T., Desai, A., Piano, F., Gunsalus, K.C., and K. Oegema. A high-resolution C. elegans essential gene network based on phenotypic profiling of a complex tissue. 2011. Cell. 145:470-482. PMID: 21529718.

Biography

Karen Oegema received her PhD in cell biology from the University of California, San Francisco and conducted postdoctoral work at the European Molecular Biology Laboratory in Heidelberg and the Max Planck Institute for Cell Biology & Genetics in Dresden. She was a Pew fellow in the Biomedical Sciences and is a recipient of the American Society of Cell Biology WICB Early and Mid-Career Awards. She is a monitoring editor for the Journal of Cell Biology and a lifetime fellow of the American Society for Cell Biology.

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