Vice-Chair, Biomedical Sciences; Professor of Cellular & Molecular Medicine
Ph.D., U.C. San Francisco
We are studying the mechanisms that direct accurate segregation of the replicated genome during cell division. Errors in this process result in aneuploidy, an incorrect complement of chromosomes that is a likely contributor to the development of cancers. For segregation, the replicated genome is packaged into condensed chromosomes, each of which is comprised of a connected pair of sister chromatids. A large multi-protein assembly called the kinetochore assembles at the centromere of each chromatid to form the primary attachment site for microtubule polymers of the spindle. We are investigating two major questions: a) How is the region where the kinetochore assembles on the chromosome specified?; b) How is this initial specification propagated to build the dynamic mechanical interface with spindle microtubules? Our studies use the early embryo of the nematode Caenorhabditis elegans, human tissue culture cells, and the budding yeast Saccharomyces cerevisiae to address these questions. Our approaches include imaging assays to monitor chromosome dynamics in living cells, in vivo perturbations using genetics/RNA interference, and biochemical analysis of kinetochore protein complexes.
BMS Focus Areas:
1. Gassmann R, Essex A, Hu J, Maddox P, Motegi F, Sugimoto A, O'Rourke S, Bowerman B, McLeod I, Yates J, Oegema K, Cheeseman I, A Desai. 2008. A new mechanism controlling kinetochore-microtubule interactions revealed by comparison of two dynein/dynactin-targeting components: SPDL-1 and the Rod/Zwilch/Zw10 complex. Genes Dev. 22:2385-99.
2. Dumont J, Oegema K, Desai A. 2010. A kinetochore-independent mechanism drives anaphase chromosome separation during acentrosomal meiosis. Nat Cell Biol. 12:894-901.
3. Gassmann R, Holland A, Varma D, Wan X, Cleveland D, Oegema K, Salmon ED, Desai A. 2010. Removal of Spindly from microtubule-attached kinetochores controls spindle checkpoint silencing in human cells. Genes Dev. 24:957-71
4. Espeut J, Cheerambathur D, Krenning L, Oegema K, Desai A. 2012. Microtubule binding by KNL-1 contributes to spindle checkpoint silencing at the kinetochore. J. Cell Biol. 196:469-82.
5. Gassmann R, Rechtsteiner A, Yuen K, Egelhofer T, Muroyama A, Barron F, Maddox P, Monen J, Ercan S, Oegema K, Lieb J, Strome S@, Desai A@. 2012. An inverse relationship to germline transcription defines centromeric chromatin in C. elegans. Nature 484(7395):534-7. (@co-corresponding authors).
6. Campbell C, Desai A. 2013. Tension sensing by Aurora B kinase is independent of survivin-based centromere localization. Nature 497(7447):118-21.