Michael Lampson,
Ph. D.

Assistant Professor of Biology
Ph.D. Cornell University, Weill Medical College, 2002

204-I Carolyn Lynch Laboratory
Department of Biology
University of Pennsylvania
Philadelphia, PA 19104 USA

V	+1 215 746.3040
F	+1 215 898.8780
E	lampson@sas.upenn.edu

cell division, intracellular signaling, meiosis

Our research focuses on molecular mechanisms that maintain genomic integrity during cell division. The replicated chromosomes are physically segregated at each division to create two genetically identical daughter cells. Segregation errors lead to loss or gain of whole chromosomes in the daughter cells, or aneuploidy, which is strongly associated with human cancer, developmental disease, and infertility. A complex and highly dynamic cellular machinery ensures accurate chromosome segregation. While many of the key components have been identified, we now face the challenge of understanding how the system is controlled. Using high-resolution light microscopy, FRET-based biosensors, and molecular perturbations introduced by RNAi or with small molecules, we are examining key processes in cell division in real time in living cells. Research in the lab is currently focused in two directions, as detailed below.

First, mitotic kinases and phosphatases are critical for the regulation of cell division, and we are developing probes based on fluorescence resonance energy transfer (FRET) to examine signaling networks at specific intracellular structures in living cells. A core project in the lab is to examine signaling at the centromere, the site on each chromosome that attaches to the mitotic spindle. Accurate chromosome segregation requires that each replicated chromosome pair attaches to spindle microtubules in the correct configuration (see figure), so that sister chromosomes are pulled in opposite directions at anaphase. Attachment errors must be (1) detected, to activate the spindle checkpoint, and (2) corrected before anaphase onset. Both processes depend on signaling at individual centromeres. We have shown that the mitotic kinase Aurora B can act as a tension sensor to regulate microtubule interactions (Liu et al. 2009). Building on these findings, we are developing models for site-specific signaling networks, involving both kinases and phosphatases, that control cell division.

Mitotic spindle with incorrect attachments between kinetochores (red) and microtubules (green) due to Aurora B inhibition

Second, we are addressing questions specific to meiotic cell cycles. These projects cover a variety of topics. Examples include the functions of cell division proteins with meiosis-specific forms, questions related to the unusual process of spindle assembly and chromosome alignment, stability of structures such as cohesin complexes that must persist for months or years in meiosis I, and evolutionary implications of non-random chromosome segregation. In collaboration with Richard Schultz (also in the Department of Biology), we are using mouse oocytes as a model system. These projects provide an opportunity to study cell division in a system with some critical differences that distinguish it from the extensively studied mitotic cell cycles.

selected publications

Chiang T, Schultz R, Lampson MA. 2011. Age-dependent susceptibility of chromosome cohesion to premature separase activation in mouse oocytes. Biology of Reproduction, in press.

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).

Salimian KJ, Ballister ER, Smoak EM, Wood S, Panchenko T, Lampson MA*, Black BE*. 2011. Feedback Control in Sensing Chromosome Biorientation by the Aurora B Kinase. Current Biology 21(13):1158-65. *Corresponding authors.

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 R, 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. Science 323:1350-3. *Corresponding author.

Duncan FE, Chiang T, Schultz RM, Lampson MA. 2009. Evidence That a Defective Spindle Assembly Checkpoint Is Not the Primary Cause of Maternal Age-Associated Aneuploidy in Mouse Eggs. Biology of Reproduction 81(4):768-76.

Fuller BG, Lampson MA*, Foley EA, Rosasco-Nitcher S, Le KV, Tobelmann P, Brautigan DL, Stukenberg PT, Kapoor TM. 2008. Midzone activation of aurora B in anaphase produces an intracellular phosphorylation gradient. Nature 453:1132-6. *Shared first author and co-corresponding author.

Kapoor TM, Lampson MA, Hergert P, Cameron L, Cimini D, Salmon ED, McEwen BF, Khodjakov, A. 2006. Chromosomes can congress to the metaphase plate before biorientation. Science (New York, N.Y.) 311:388-91 (Cover).