Terry Lechler , Ph.D. (Harvard University)
Associate Professor, Department of Dermatology
Associate Professor, Department of 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 several basic questions related to the development and morphogenesis of these epithelia.
1. Spindle Orientation/Asymmetric Cell Division in the Epidermis
Regulation of spindle orientation is used in many tissues to generate cell fate diversity through asymmetric cell divisions as well as to promote proper tissue architecture. The skin uses these divisions to stratify the epidermis, specify stem cells and form hair follicles. Our lab studies the cell biology of how mitotic spindle positioning is controlled, how these divisions are regulated developmentally and the consequences of loss of spindle orientation on tissue development, homeostasis and regeneration.
2. Regulation of Centrosomes and Microtubule Organization
As cells differentiate they change their shape and the organization of their internal cytoskeleton, including microtubules. We are studying both how centrosomal and non-centrosomal microtubule arrays are formed in cells, we are using genetics to understand the functions of these arrays, and we are determining how differentiation signals impact the composition and function of centrosomes and microtubules.
3. Cell-cell Adhesion
We study cell adhesion structures including adherens junctions, tight junctions and desmosomes and their interplay with underlying cytoskeletal structures. We are particulary interested in functions of the desmosome and how these are disrupted under disease conditions.
Our studies are multi-disciplinary and span from mouse genetics to in vitro reconstitution experiments. This allows us not only to understand molecular mechanisms and dynamics, 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.
Muroyama A, Terwilliger M, Dong B, Suh H, Lechler T (2018) Genetically induced microtubule disruption in the mouse intestine impairs intracellular organization and transport. Mol Biol Cell. 2018 Jul 1;29(13):1533-1541.
Sumigray KD, Terwilliger M, Lechler T (2018) Morphogenesis and Compartmentalization of the Intestinal Crypt. Dev Cell. 2018 Apr 23;45(2):183-197.
Muroyama A, Lechler T (2017) A transgenic toolkit for visualizing and perturbing microtubules reveals unexpected functions in the epidermis. Elife. 2017 Sep 4;6. pii: e29834.
Muroyama A, Lechler T (2017) Microtubule organization, dynamics and functions in differentiated cells. Development. 2017 Sep 1;144(17):3012-3021
Muroyama A, Seldin L, Lechler T (2016) Divergent regulation of functionally distinct γ-tubulin complexes during differentiation. J Cell Biol. 2016 Jun 20;213(6):679-92
Seldin L, Muroyama A, Lechler T (2016). NuMA-microtubule interactions are critical for spindle orientation and the morphogenesis of diverse epidermal structures. Elife. 2016 Jan 14;5. pii: e12504. [Epub ahead of print]
Morrow A, Lechler T (2015). Studying cell biology in the skin. Mol Biol Cell. 26(23):4183-6
Zhou K, Sumigray KD, Lechler T (2015). The Arp2/3 complex has essential roles in vesicle trafficking and transcytosis in the mammalian small intestine. Mol Biol Cell. 26(11):1995-2004
Sumigray KD, Lechler T (2015). Cell adhesion in epidermal development and barrier formation. Curr Top Dev Biol. 112:383-414
Lechler T (2014). Arp2/3 complex function in the epidermis. Tissue Barriers. 2(4):e944445
Sumigray K, Zhou K, Lechler T (2014). Cell-cell adhesions and cell contractility are upregulated upon desmosome disruption. PLoS One. 9(7):e101824
Huebner RJ, Lechler T, Ewald AJ (2014). Developmental stratification of the mammary epithelium occurs through symmetry-breaking vertical divisions of apically positioned luminal cells. Development. 141(5):1085-94
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 (2013). Actin-related protein2/3 complex regulates tight junctions and terminal differentiation to promote epidermal barrier formation. Proc Natl Acad Sci USA. 110(40):E3820-9
Foote HP, Sumigray KD, Lechler T (2013). FRAP Analysis Reveals Stabilization of Adhesion Structures in the Epidermis Compared to Cultured Keratinocytes. PLoS One. 8(8):e71491.
Ray S, Foote HP, Lechler T (2013). beta-Catenin protects the epidermis from mechanical stresses. J Cell Biol. 202(1):45-52.