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Michael Lampson
Assistant Professor, Dept of Biology
Cancer
Biology Program
Address
204-I Carolyn Lynch Laboratory (office)
211 Carolyn Lynch Laboratory (lab)
433 South University Ave.
Philadelphia, PA 19104-6069
Office tel.: 215-746-3040
Lab tel.: 215-898-3693
Fax: 215-898-8780
E-mail: lampson@sas.upenn.edu
Link
Dr.
Lampson's Biology Department Page
Education
Harvard University : B.A. (Physics), 1994.
Cornell University, Weill Medical College: Ph.D. (Physiology and Biophysics), 2002.
Rockefeller University: Postdoctoral Fellow (Cell Biology), 2006.
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Research Interests
- cell division, intracellular signaling
Key words:cell
division, mitosis, meiosis, chromosome segregation, kinase
signaling, microscopy
Description of
Research
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 and developmental disease. A complex and highly dynamic
cellular machinery ensures accurate chromosome segregation,
with many events occurring on minute or second timescales.
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 will examine key processes in cell
division in real time in the context of living mammalian cells.
Mitotic kinases are critical for the regulation of these processes,
and we are developing probes based on fluorescence resonance
energy transfer (FRET) to examine kinase signaling networks
at specific intracellular structures, such as centromeres
and spindle poles, 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 of these processes
require that correct and incorrect attachments be distinguished.
We will test the hypothesis that this distinction is made
through differential signaling by mitotic kinases at individual
centromeres. Starting with this project, we hope to develop
models for site-specific signaling neworks that control critical
processes in cell division.
Spindles with correct (left) and incorrect
(right) chromosome attachments, with microtubules shown in
green and chromosomes in blue (from Lampson et al. 2004).
Selected Publications
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.
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.
Search PubMed for more articles
Lab
Rotation
Projects
- Develop FRET-based probes for mitotic kinases to examine signaling networks at centromeres and centrosomes in living cells.
- Analyze the contributions of protein kinases and phosphatases to phosphorylation dynamics in mitosis.
- Examine chromosome and spindle dynamics in Meiosis I in mouse oocytes by live imaging.
- Lab personnel:
Teresa Chiang, graduate student
Dan Liu, postdoc
Enxiu Wang, postdoc
Kim Le, technician
Laura Kelly, undergraduate
Brian Young, undergraduate
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