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, combined with molecular perturbations introduced by RNAi or with small molecule inhibitors, 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.

Second, we are addressing the question of why female fertility decreases with age. The best evidence to date is that the decreased fertility is due to an increase in the production of aneuploid eggs by older females (both human and mouse), which clearly points to chromosome segregation defects as an underlying cause. Together with Richard Schultz (also in the Department of Biology), we are using mouse oocytes as a model system to understand the defects leading to aneuploidy. Our goal is to focus on basic molecular mechanisms involved in meiotic chromosome segregation, such as the spindle checkpoint, kinetochore function, and cohesion, but the relevance for reproductive health is obvious. This project provides an opportunity to study cell division in a system that has clear importance for human health, the mammalian oocyte, but that has received relatively little attention compared to some other model systems. We will address both the age-associated increase in aneuploidy, which is currently quite mysterious, and basic mechanisms of meiosis.

selected publications

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, in press.
*Corresponding author

Macůrek L, Lindqvist A, Lim D, Lampson MA, Klompmaker R, Freire R, Clouin C, Taylor SS, Yaffe MB, Medema RH. 2008. Polo-like kinase-1 is activated by aurora A to promote checkpoint recovery. Nature 455:119-23.

Fuller, B.G., Lampson, M.A.*, Foley, E.A., Rosasco-Nitcher, S., Le, K.V., Tobelman, P., Brautigan, D.L., Stukenberg, P.T., and Kapoor, T.M. (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, T.M., Lampson, M.A., Hergert, P., Cameron, L., Cimini, D., Salmon, E.D., McEwen B.F., and Khodjakov, A. (2006) Chromosomes can congress to the metaphase plate prior to bi-orientation. Science 311: 388-91.

Lampson, M.A. and Kapoor, T.M. (2006) Unraveling cell division mechanisms with small-molecule inhibitors. Nature Chemical Biology 2: 19-27.

Lampson, M.A. and Kapoor, T.M. (2005) The human mitotic checkpoint protein BubR1 regulates chromosome-spindle attachments. Nature Cell Biology 7: 93-8.

Lampson, M.A., Renduchitala, K., Khodjakov, A., and Kapoor, T.M. (2004) Correcting improper chromosome–spindle attachments during cell division. Nature Cell Biology 6: 232-7.