Ph.D., Cornell University, Weill Medical College, 2002
AB, Harvard College, 1994
For more information, visit the lab webpage
Within the broad theme of cell division, our research is currently focused in two areas:
1. Mechanics of cell division, particularly interactions between chromosomes and spindle microtubules and regulation by mitotic kinases.
2. Cell biological principles driving chromosome evolution through biased (i.e., non-Mendelian) chromosome segregation in meiosis.
Regulation of kinetochore-microtubule interactions is crucial for accurate chromosome segregation and maintenance of genome integrity. We use a variety of experimental approaches to manipulate enzymatic activities, such as kinases, at kinetochores and to measure the effects of these perturbations in living cells. Examples include chemically-induced dimerization to recruit activities to kinetochores with precise temporal control, FRET-based biosensors that report on phosphorylation changes with high temporal and spatial resolution in live cells, and photoactivatable fluorescent proteins to measure protein dynamics. We are also reconstituting a diffusion based signaling mechanism for a key mitotic kinase, Aurora B, from purified components in vitro. We exploit these experimental tools to develop and test mathematical models for kinase signaling and microtubule dynamics.
A second research area is nonrandom chromosome segregation in meiosis, also known as meiotic drive. Because of the inherent asymmetry of female meiosis, only chromosomes that segregate to the egg go into a gamete. Any bias away from random segregation, in violation of Mendel’s First Law, is therefore under strong positive selection and has significant consequences for centromere and karyotype evolution and for speciation. Despite the importance of the phenomenon, the mechanistic basis for nonrandom segregation is mysterious. We are using Robertsonian fusions in mouse oocytes as a model to understand the cell biological mechanisms underlying meiotic drive, how the direction of drive is determined, and (most intriguingly) how it can switch, leading to dramatic changes in karyotype. Our work is providing the first insight into mechanisms underlying meiotic drive in animals, link the basic cell biology of chromosome segregation to karyotype evolution and speciation.
Davydenko O, Schultz RM, Lampson MA. 2013. Increased CDK1 activity determines the timing of kinetochore-microtubule attachments in meiosis I. Journal of Cell Biology 202(2):221-9.
Liu D, Davydenko O, Lampson MA. 2012. Polo-like kinase-1 regulates kinetochore-microtubule dynamics and spindle checkpoint silencing. Journal of Cell Biology 198(4):491-9.
Schindler K, Davydenko O, Fram B, Lampson MA*, Schultz RM*. 2012. Maternally-recruited Aurora C kinase is more stable than Aurora B to support mouse oocyte maturation and early development. Proceedings of the National Academy of Sciences 109(33):E2215-22 (Cover). *Shared corresponding authors.
Chiang T, Schultz R, Lampson MA. 2012. Meiotic Origins of Maternal Age-Related Aneuploidy. Biology of Reproduction 86(1):1-7.
Wang E, Ballister E, Lampson MA. 2011. Aurora B dynamics at centromeres creates a diffusion-based phosphorylation gradient. Journal of Cell Biology 194(4):539-549 (Cover).
Lampson MA, Cheeseman IM. 2011. Sensing centromere tension: Aurora B and the regulation of kinetochore function. Trends in Cell Biology 21(3):133-40.
Chiang T, Duncan FE, Schindler K, Schultz RM, Lampson MA. 2010. Evidence that weakened centromere cohesion is a leading cause of age-related aneuploidy in oocytes. Current Biology 20(17):1522-8.
Liu D, Vleugel M, Backer CB, Hori T, Fukagawa T, Cheeseman IM, Lampson MA. 2010. Regulated targeting of protein phosphatase 1 to the outer kinetochore by KNL1 opposes Aurora B kinase. Journal of Cell Biology 188(6):809-20 (Cover).
Liu D, Vader G, Vromans MJ, Lampson MA*, Lens SM. 2009. Sensing chromosome bi-orientation by spatial separation of Aurora B kinase from kinetochore substrates. Science323:1350-3. *Corresponding author.
BIOL 121 (Introductory Biology - Molecular Biology of Life)
BIOL 486 / CAMB 486 (Chromosomes and the Cell Cycle)