Terry Lechler , Ph.D. (Harvard University)
Associate Professor, Department of Dermatology
Associate Professor, Cell Biology
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.
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.
Seldin L, Poulson ND, Foote HP, Lechler T (2013) NuMA localization, stability and function in spindle orientation involves 4.1 and Cdk1 interactions. Mol Biol Cell. Epub
Zhou K, Muroyama A, Underwood J, Leylek R, Ray S, Soderling SH, Lechler T. Actin-related protein2/3 complex regulates tight junctions and terminal differentiation to promote epidermal barrier formation.Proc Natl Acad Sci U S A. 2013 Sep 16. [Epub ahead of print]
Foote HP, Sumigray KD, Lechler T. FRAP Analysis Reveals Stabilization of Adhesion Structures in the Epidermis Compared to Cultured Keratinocytes.PLoS One. 2013 Aug 19;8(8):e71491. doi: 10.1371/journal.pone.0071491. PMID: 23977053
Ray S, Foote HP, Lechler T. beta-Catenin protects the epidermis from mechanical stresses.J Cell Biol. 2013 Jul 8;202(1):45-52. doi: 10.1083/jcb.201212140. Epub 2013 Jul 1. PMID: 23816618
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.
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.
Muroyama, A. and Lechler, T. 2012. Polarity and Stratification of the Epidermis. Seminars in Cell and Developmental Biology, 23:890-896.
Poulson ND and T. Lechler. 2012. Asymmetric cell divisions in the epidermis. Int Rev Cell Mol Biol., 295:199-232.
Lechler, T. 2012. Adherens Junctions and Stem Cells. Subcellular Biochemistry, 60:359-377.
Sumigray KD and T. Lechler. 2011. Control of cortical microtubule organization and desmosome stability by centrosomal proteins. Bioarchitecture, 1:221-224.
Ray S and T. Lechler. 2011. Regulation of asymmetric cell division in the epidermis. Cell Division, 6:12.
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.
Poulson, N. D. and T. Lechler. (2010). Robust control of mitotic spindle orientation in the developing epidermis. Journal of Cell Biology, 191:915-22.