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Duke University


Duke Medical Center

Terry Lechler , Ph.D.
(Cell and Developmental Biology, Harvard University)

Assistant Professor, Cell Biology

Terry Lechler

Email
Lechler@cellbio.duke.edu

310 Nanaline Duke Bldg., Box 3709, Duke University Medical Center, Durham, NC 27710

Telephone (919) 684-4550

 

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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    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.

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.



Selected Recent Publications
Sumigray KD, Foote HP and T. Lechler. 2012. Noncentrosomal microtubules and type II myosins potentiate epidermal cell adhesion and barrier formation. Journal of Cell Biology, 199:513-525. -PDF-

Sumigray KD and T. Lechler. 2012. Desmoplakin controls microvilli length but not cell adhesion or keratin organization in the intestinal epithelium. Molecular Biology of the Cell, 23:792-9. -PDF-

Muroyama, A. and Lechler, T.  2012. Polarity and Stratification of the Epidermis. Seminars in Cell and Developmental Biology, 23:890-896. -PDF-

Poulson ND and T. Lechler. 2012. Asymmetric cell divisions in the epidermis. Int Rev Cell Mol Biol., 295:199-232. -PDF-

Lechler, T.  2012. Adherens Junctions and Stem Cells. Subcellular Biochemistry, 60:359-377. -PDF-

Sumigray KD and T. Lechler. 2011. Control of cortical microtubule organization and desmosome stability by centrosomal proteins. Bioarchitecture, 1:221-224. -PDF-

Ray S and T. Lechler. 2011. Regulation of asymmetric cell division in the epidermis. Cell Division, 6:12. -PDF-

Sumigray, K.D., H. Chen and T. Lechler.  (2011).  Lis1 is essential for cortical microtubule organization and desmosome stability in the epidermis. Journal of Cell Biology, 194:631-42. -PDF-

Poulson, N. D. and T. Lechler. (2010). Robust control of mitotic spindle orientation in the developing epidermis.  Journal of Cell Biology, 191:915-22. -PDF-

Sumigray KD and T. Lechler. 2010. Dissecting cell adhesion cross-talk with micropatterns. Proc Natl Acad Sci, 107:13199-200. -PDF-

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.


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