- Postdoctoral Fellow, Harvard University, 2003-2008
- Ph.D., MIT, 2003
Biology Bldg. A315
Lacefield Lab website
IU Trustees Teaching Award, 2013
Basil O'Connor Award, March of Dimes Foundation, 2010
Errors in chromosome segregation can have devastating consequences. In mitosis, chromosomal instability is a hallmark of cancer. In meiosis, chromosome mis-segregation can result in trisomy conditions such as Down syndrome, the leading genetic cause of developmental disability. The goal of our research is to understand the mechanisms the cell uses to ensure faithful chromosome segregation in mitosis and meiosis. We are studying how the cell prevents errors in chromosome segregation, including how chromosomes properly attach to the spindle in both meiotic divisions and the monitoring of this attachment by the spindle checkpoint. Many of the genes involved in these processes are conserved, allowing us to use the powerful genetic tools of the budding yeast, S. cerevisiae.
Chromosomes attach to the meiotic spindle at the kinetochore, the protein complexes built on centromeric regions of DNA. We are interested in the proteins that regulate this connection in meiosis. For example, in the first meiotic division (meiosis I), the kinetochores on paired homologous chromosomes must be bound to microtubules from opposite poles of the spindle, but in meiosis II, the kinetochores of sister chromatids must be bound to opposite poles. Furthermore, to prevent chromosome missegregation, if the kinetochores on homologous chromosomes attach to microtubules from the same spindle pole, one kinetochore must release and re-attach properly. The spindle checkpoint monitors this connection and, if the attachment of microtubules to kinetochores is defective, halts the cell cycle to allow time to correct the error. We are studying the regulation of the proteins within the kinetochore to execute each of these steps: microtubule binding to homologous chromosomes in meiosis I and sister chromatids in meiosis II, sensing inappropriate microtubule attachment, signaling the checkpoint, and correcting the error.
In meiosis, the spindle checkpoint proteins not only act in a surveillance system to ensure that chromosomes are properly attached to the spindle, but they also have additional roles. Certain spindle checkpoint proteins are involved in ensuring that kinetochores can initially attach to the bipolar spindle. Other spindle checkpoint proteins are also involved in the timing of the meiotic cell cycle. We are interested in understanding how the different roles of the spindle checkpoint proteins are executed.
Gavade, JN, Puccia, CM, Herod, SG, Trinidad, JC, Berchowitz, LE, and Lacefield, S. Identification of 14-3-3 Proteins, Polo kinase, and RNA-binding protein Pes4 as Key Regulators of Meiotic Commitment in Budding Yeast. Current Biology (in press).
Gihana, GM, Cross-Najafi, A and Lacefield, S. The Mitotic Exit Network Regulates the Spatiotemporal Activity of Cdc42 to Maintain Cell Size. Journal of Cell Biology 220(1):e202001016 (2021).
MacKenzie AM and Lacefield S. CDK regulation of meiosis: Lessons from S. cerevisiae and S. pombe. Genes 11(7):723 (2020).
Cairo G and Lacefield S. Establishing correct kinetochore-microtubule attachments in mitosis and meiosis. Essays in Biochemistry 64(2) 277-287 (2020).
Cairo G, MacKenzie A, and Lacefield S. Differential requirement of Bub1/Bub3 in the regulation of meiotic versus mitotic chromosome segregation. Journal of Cell Biology 219 (4):e201909136 (2020).
Wang F, Zhang R, Feng W, Tsuchiya D, Ballew O, Li J, Denic V, Lacefield S. Autophagy of an amyloid-like translational repressor regulates meiotic exit. Developmental Cell 52:141-151 (2020).
Ballew O and Lacefield S. The DNA damage checkpoint and the spindle position checkpoint maintain meiotic commitment in Saccharomyces cerevisiae. Current Biology 29: 1-12 (2019).
Lacefield S. Detaching the tether: remodeling mitochondrial localization during meiosis. Journal of Cell Biology. 218(2) (2019).
Barsh GS, Bhalla N, Cole F, Copenhaver GP, Lacefield S, Libuda DE. 2018 PLOS Genetics Research Prize: Bundling, stabilizing, organizing—The orchestration of acentriolar spindle assembly by microtubule motor proteins. PLOS Genetics 14(9):e1007649 (2018).
Gihana GM, Musser TR, Thompson O, and Lacefield S. Prolonged CDK inhibition results in septin perturbations during return-to-growth and mitosis. Journal of Cell Biology (2018).
Lacefield S. Chromosome biology: specification of the kinetochore for cohesion recruitment. Current Biology 27 (24): R1319-R1321 (2017).
Falk JE, Tsuchiya D, Verdaasdonk J, Lacefield S, Bloom K, Amon, A. Spatial signals link exit from mitosis to spindle position. Elife 5. pii:e14036 (2016)
Yang Y, Tsuchiya D, and Lacefield S. Bub3 promotes Cdc20-dependent activation of the APC/C in S. cerevisiae. Journal of Cell Biology 209(4): 519-527 (2015).
This paper was featured in the JCB Biobytes podcast.
Ho KH, Tsuchiya D, Oliger AC, and Lacefield S. Localization and function of budding yeast CENP-A depends on kinetochore protein interactions and is independent of canonical centromere sequence. Cell Reports 9(6): 2027-2033 (2014).
This paper was recommended by F1000.
Tsuchiya D, Yang Y, and Lacefield S. Positive feedback of NDT80 expression ensures irreversible meiotic commitment in budding yeast. PLOS Genetics 10 (6): e1004398 (2014).
Tsuchiya D and Lacefield S. Cdk1 modulation ensures the coordination of cell-cycle events during the switch from meiotic prophase to mitosis. Current Biology 23 1505-1513 (2013).
Tsuchiya D, Gonzalez C, and Lacefield S. The spindle checkpoint protein Mad2 regulates APC/C activity during prometaphase and metaphase of meiosis I in S. cerevisiae. Molecular Biology of the Cell 22 (16): 2848-2861 (2011). This paper was chosen for “Highlights in MBoC” by the editorial board.
This paper was recommended by F1000.