Michael Lampson

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Assistant Professor of Biology
Department: Biology

Contact information
Department of Biology
University of Pennsylvania
433 South University Ave.
Philadelphia, PA 19104
Office: 215-746-3040
Education:
A.B. (Physics)
Harvard University, 1994.
Ph.D. (Physiology and Biophysics)
Cornell University, 2002.
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Description of Research Expertise

Research Interests: cell division, chromosome evolution

Keywords: mitosis, meiosis, centromere, kinetochore, cytoskeleton, meiotic drive, microscopy, FRET

Research Details:

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.

For more information: https://sites.sas.upenn.edu/lampson-lab/pages/research

Rotation Projects:
Please contact Dr. Lampson to discuss potential rotation projects.

Lab Personnel:
Ed Ballister, PhD student
Maomao Zhang, PhD student
Lukas Chmatal, PhD student
Evan Smoak, PhD student (co-mentored with Dr. Ben Black)
Dario Segura-Pena, postdoctoral fellow
Michelle Riegman, masters student
Alyssa Mayo, research specialist
Priyanka Kothari, undergraduate
Karren Yang, undergraduate
Jonathan Bell, undergraduate

Selected Publications

Davydenko Olga, Schultz Richard M, Lampson Michael A: Increased CDK1 activity determines the timing of kinetochore-microtubule attachments in meiosis I. The Journal of cell biology 202(2): 221-9, Jul 2013.

Liu Dan, Davydenko Olga, Lampson Michael A: Polo-like kinase-1 regulates kinetochore-microtubule dynamics and spindle checkpoint silencing. The Journal of cell biology 198(4): 491-9, Aug 2012.

Schindler Karen, Davydenko Olga, Fram Brianna, Lampson Michael A*, Schultz Richard M*: 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 of the United States of America 109(33): E2215-22, Aug 2012 Notes: Cover. *Corresponding authors.

Chiang Teresa, Schultz Richard M, Lampson Michael A: Meiotic origins of maternal age-related aneuploidy. Biology of reproduction 86(1): 1-7, Jan 2012.

Wang Enxiu, Ballister Edward R, Lampson Michael A: Aurora B dynamics at centromeres create a diffusion-based phosphorylation gradient. The Journal of cell biology 194(4): 539-549, Aug 2011 Notes: Cover.

Chiang Teresa, Schultz Richard M, Lampson Michael A: Age-dependent susceptibility of chromosome cohesion to premature separase activation in mouse oocytes. Biology of reproduction 85(6): 1279-83, Dec 2011.

Lampson Michael A, Cheeseman Iain M: Sensing centromere tension: Aurora B and the regulation of kinetochore function. Trends in cell biology 21(3): 133-40, Mar 2011.

Chiang Teresa, Duncan Francesca E, Schindler Karen, Schultz Richard M, Lampson Michael A: Evidence that weakened centromere cohesion is a leading cause of age-related aneuploidy in oocytes. Current biology 20(17): 1522-8, Sep 2010.

Liu Dan, Vleugel Mathijs, Backer Chelsea B, Hori Tetsuya, Fukagawa Tatsuo, Cheeseman Iain M, Lampson Michael A: Regulated targeting of protein phosphatase 1 to the outer kinetochore by KNL1 opposes Aurora B kinase. The Journal of cell biology 188(6): 809-20, Mar 2010 Notes: Cover.

Liu Dan, Vader Gerben, Vromans Martijn J M, Lampson Michael A*, Lens Susanne M A: Sensing chromosome bi-orientation by spatial separation of aurora B kinase from kinetochore substrates. Science (New York, N.Y.) 323(5919): 1350-3, Mar 2009 Notes: *Corresponding author.

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Last updated: 12/05/2013
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