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Cell
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Duke
University
Duke
Medical Center
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| Terry
Lechler ,
Ph.D.
(Cell
and Developmental Biology, Harvard University)
Assistant
Professor, Cell Biology
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Our lab is studying the morphogenesis of epithelia
- the cells/tissues that cover our body and line our
internal organs. We study two highly proliferative
tissues, the skin and the intestine. Both of these
tissues turn over rapidly throughout adulthood, contain
stem cells that contribute to tissue homeostasis and
both are common sites for cancer development. However,
they have very different functions (skin forms a barrier,
while the intestine absorbs nutrients) and very different
morphologies. We want to understand how both cell shape
and three-dimensional organization of cells is achieved
to meet these diverse functions. The lab studies two
basic questions related to the development and morphogenesis
of these epithelia. |
1.
Asymmetric Cell Division in the Epidermis
During embryonic development, epidermal cells can divide either symmetrically
or asymmetrically. The asymmetric divisions promote stratification (formation
of multiple cell layers) and differentiation of the epidermis. We want to understand
how these cells divide asymmetrically - how stereotypical orientations of the
mitotic spindle are achieved, and how loss of asymmetric divisions affects tissue
morphogenesis. |
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Email
Lechler@cellbio.duke.edu
310 Nanaline Duke Bldg., Box
3709, Duke University Medical Center, Durham, NC 27710
Telephone (919)
684-4550 |
2.
Microtubule Organization and Cell Polarity
As cells differentiate they often change both their shape and the organization
of their internal cytoskeleton. In epidermis, cells become more squamous (flat)
and microtubules become associated with sites of cell adhesion. In the intestine,
the differentiated cells are columnar and have microtubules oriented for transport
of substances to the apical or basal end of the cell. We are studying how these
diverse organizations are created and what happens to these tissues if they cannot
organize their cytoskeleton correctly.
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We
use the mouse and cultured cells as our primary models
for these studies. This combination allows us not only
to understand molecular mechanisms, but also to understand
the physiological consequence when they are disrupted
in an animal. Using conditional knockout and transgenic
technology, we can both observe the morphogenetic process
in living animals/tissues and understand its molecular
basis. A combination of live cell and animal imaging,
cell biology, organ culture, mouse genetics and biochemistry
are used to address these problems. |
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Selected
Recent Publications
Lechler, T. and E. Fuchs.
(2007). Desmoplakin: An unexpected regulator of microtubule
organization in the epidermis. Journal of Cell Biology,
176:147-54. -PDF-
Lechler, T. and E. Fuchs. (2005). Asymmetric cell
divisions promote stratification and differentiation of
mammalian skin. Nature, 437:275-280.
Tinkle, C. L.*, T.
Lechler*, H.A. Pasolli, E. Fuchs. (2004). Conditional targeting
of E-cadherin in skin: Insights into hyperproliferative
and degenerative responses. Proc. Natl. Acad. Sci. USA,
101:552-557. *co-authorship.
Lechler, T., G.A. Jonsdottir, S.K. Klee, D. Pellman,
and R. Li. (2001). A two-tiered mechanism by which Cdc42
controls the localization and activation of an Arp2/3-activating
motor complex in yeast. Journal of Cell Biology, 155:261-70.
Lechler,
T., A. Shevchenko, A. Shevchenko, and R. Li. (2000).
Direct Involvement of yeast type I myosins in Cdc42-dependent
actin polymerization. Journal of Cell Biology, 148:363-373.
Winter,
D.*, T. Lechler*, and R. Li. (1999). Activation of the
yeast Arp2/3 complex by Bee1p, a WASP-family protein.
Current Biology, 9:501-504. *co-authorship.
Lechler, T.,
and R. Li. (1997). In vitro reconstitution of cortical
actin assembly sites in budding yeast. Journal of Cell
Biology, 138:95-103.
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