![\"Williams](\"https:\/\/www.med.unc.edu\/pathology\/wp-content\/uploads\/sites\/646\/2018\/04\/williams-figure-1.jpeg\" "\\"Williams")
<\/p>\nThe mammalian skin epithelium (epidermis) is an ideal model system to study fundamental questions in stem cell and cancer biology. It is accessible; it can be cultured, genetically manipulated and transplanted; and its resident stem cells possess unparalleled regenerative capacity. Our skin, unlike many other organs, undergoes continuous growth and turnover. And unlike other \u201csimple\u201d epithelia, the epidermis is stratified, consisting of many cell layers with specialized functions. In development and homeostasis, progenitors in the skin must balance self-renewal and differentiation programs. We have found that asymmetric cell divisions are a critical mechanism by which skin progenitors maintain this equilibrium. We are interested in studying how this asymmetry is controlled at a molecular level, and how division orientation impacts cell fate choices in normal and neoplastic growth. To facilitate these and other studies in diverse epithelia, we have developed a powerful functional tool,\u00a0in utero\u00a0<\/i>lentiviral RNAi (see figure, below), which allows us to rapidly perform functional studies on any gene in the intact mouse in weeks instead of years. Our broad goal will be to use this technique, in combinations of candidate and screening approaches, to dissect pathways that influence epithelial differentiation.<\/p>\n
Beyond studying how division orientation influences epidermal development, we also study the role that the spindle orientation complex plays in other tissues, including the cerebellum and oral epithelia. In addition, we have broad interests in studying the mechanisms that control the formation and maintenance of stratified epithelia in the context of development, stem cell function, and disease. Two particular areas of great interest are head and neck cancers, and cleft lip and palate.<\/p>\n
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Williams SE<\/strong>\u00a0and Lough KJ. Cell biology: Pardon the\u00a0intrusion.\u00a0Curr Bio<\/em>l\u00a02020 Dec 21; 30(24): R1481-4. doi: 10.1016\/j.cub.2020.10.036.\u00a0PMID: 33352130<\/a><\/p>\n Lough\u00a0KJ, Spitzer DC, Bergman AJ, Wu JJ, Byrd KM,\u00a0Williams\u00a0SE<\/strong>. Cleft palate\u00a0is caused by disruption of the nectin-afadin cell-cell adhesion complex.\u00a0Development<\/em>\u00a02020\u00a0Jul 13; 147(21):dev.189241. \u00a0[Special issue\u00a0on \u201cThe Origins and Mechanisms of Developmental Disorders\u201d].\u00a0PMID:\u00a032554531<\/a><\/p>\n Lough\u00a0KJ, Byrd KM, Descovich CP, Spitzer DC, Bergman AJ, Beaudoin III GM, Reichardt\u00a0LF and\u00a0Williams SE<\/strong>. Telophase correction refines division orientation\u00a0in\u00a0stratified epithelia.\u00a0eLife<\/em>\u00a02019 Dec 13;8. pii: e49249.\u00a0PMID: 31833472<\/a><\/p>\n Byrd\u00a0KM, Piehl NC, Patel JH, Huh WJ, Sequeira I, Lough KJ, Wagner BL, Marangoni P,\u00a0Watt FM, Klein OD, Coffey RJ,\u00a0Williams SE<\/strong>. Heterogeneity within\u00a0stratified\u00a0epithelial stem cell populations maintains the oral mucosa in response to\u00a0physiological stress.\u00a0Cell Stem Cell\u00a0<\/em>2019 Dec 5; 25(6): 814-29.\u00a0PMID: 31809739<\/a><\/p>\n Carper MB,\u00a0Troutman S, Wagner BL, Byrd KM, Selitsky SR, Parag-Sharma K, Henry EC, Li W,\u00a0Parker JS, Montgomery SA, Cleveland JL,\u00a0Williams SE<\/strong>, Kissil JL,\u00a0Hayes DN,\u00a0Amelio AL. An immunocompetent mouse model of HPV16(+) head and neck squamous\u00a0cell carcinoma.\u00a0Cell Reports\u00a0<\/em>2019 Nov 5;29(6):1660-1674.e7.\u00a0PMID: 31693903<\/a><\/p>\n Lough KJ, Byrd KM, Spitzer DC, and\u00a0Williams SE<\/strong>\u00a0(2017). Closing the gap: mouse models to study adhesion in secondary palatogenesis.\u00a0J Dent Res<\/i>\u00a0[Special Issue on Orofacial Clefting, Craniofacial and Dental Anomalies] Available online August 17, 2017.\u00a0PMID: 28817360<\/a><\/p>\n Byrd KM, Lough KJ, Patel JH, Descovich CP, Curtis TA and\u00a0Williams SE<\/strong>\u00a0(2016). LGN plays distinct roles in oral epithelial stratification, filiform papilla morphogenesis and hair follicle development.\u00a0Development<\/i>\u00a0143(15): 2803-17.\u00a0PMID: 27317810<\/a>\u00a0<\/strong>[Selected for Cover, F1000 reviewed]\n Williams SE<\/strong>*, Garcia I, Crowther AJ, Stewart A, Li S, Stewart A, Liu H, Lough, KJ, O\u2019Neill S, Veleta K, Oyarzabal EA, Merrill JR, Shi YI and Gershon TR* (2015). Aspm sustains postnatal cerebellar neurogenesis and medulloblastoma growth in mice.\u00a0Development<\/i>\u00a0142(22): 3921-32.\u00a0PMID: 26450969<\/a>\u00a0<\/strong>*co-corresponding authors<\/p>\n Williams SE<\/strong>, Ratliff LA, Postiglione MP, Knoblich JA and Fuchs E (2014). Par3-mInsc and Gai3 cooperate to promote oriented epidermal cell divisions through LGN.\u00a0Nat Cell Biol<\/i>\u00a016(8): 758-69.\u00a0PMID: 25016959<\/a>\u00a0[F1000 reviewed]\n Williams SE<\/b>\u00a0and Fuchs E (2013). Oriented divisions, fate decisions.\u00a0Curr Opin Cell Biol<\/i>\u00a025(6):749\u2013758.\u00a0PMID: 24021274<\/a><\/p>\n Williams SE<\/strong>, Beronja S, Pasolli HA and Fuchs E (2011). Asymmetric cell divisions promote Notch-dependent epidermal differentiation.\u00a0Nature<\/i>\u00a0470: 353-358.\u00a0PMID: 21331036<\/a>\u00a0[Comment in\u00a0Nat Rev Genetics<\/i>\u00a012: 226; F1000 reviewed].<\/p>\n Ezratty E, Stokes N, Chai S, Shah A,\u00a0Williams SE<\/strong>\u00a0and Fuchs E (2011). A role for the primary cilium in Notch signaling and epidermal differentiation during skin development.\u00a0Cell<\/i>\u00a045: 1129-41.\u00a0PMID: 21703454<\/a><\/p>\n Luxenburg C, Pasolli HA,\u00a0Williams SE<\/strong>\u00a0and Fuchs E (2011). Developmental roles for Srf, cortical cytoskeleton and cell shape in epidermal spindle orientation.\u00a0Nat Cell Biol<\/i>\u00a013: 203-14.\u00a0PMID: 21336301<\/a>\u00a0[F1000 reviewed]\n Beronja S, Livshits G,\u00a0Williams SE<\/strong>\u00a0and Fuchs E (2010). Rapid functional dissection of genetic networks via tissue-specific transduction and RNAi in mouse embryos.\u00a0Nat Med<\/i>\u00a016: 821-7.\u00a0PMID: 20526348<\/a><\/p>\n Perez-Moreno M, Song W, Pasolli HA,\u00a0Williams SE<\/strong>\u00a0and Fuchs E (2008). Loss of p120 catenin and links to mitotic alterations, inflammation and skin cancer.\u00a0PNAS<\/i>\u00a0105: 15399-404.\u00a0PMID: 18809907<\/a>\u00a0[F1000 reviewed]\n Williams SE<\/strong>, Grumet M, Colman DR, Henkemeyer M, Mason CA, and Sakurai T (2006). A role for Nr-CAM in the patterning of binocular visual pathways.\u00a0Neuron<\/i>\u00a050: 535-47.\u00a0PMID: 16701205<\/a>\u00a0[Comment in\u00a0Neuron<\/i>\u00a050: 519-21]\n Williams SE<\/strong>, Mason CA, and Herrera E (2004). The optic chiasm as a midline choice point.\u00a0Curr Opin Neurobiol<\/i>\u00a014: 51-60.\u00a0PMID: 15018938<\/a><\/p>\n Williams SE<\/strong>, Mann F, Sakurai T, Erskine L, Wei S, Rossi DJ, Gale N, Holt CE, Mason CA, and Henkemeyer M (2003). Ephrin-B2 and EphB1 mediate retinal axon divergence at the optic chiasm.\u00a0Neuron<\/i>\u00a039: 919-935.\u00a0PMID: 12971893<\/a>\u00a0[Comment in\u00a0Neuron<\/i>\u00a039: 885-8; F1000 reviewed]\n Erskine L,\u00a0Williams SE<\/strong>, Brose K, Kidd T, Rachel RA, Goodman CS, Tessier-Lavigne M, and Mason CA (2000). Retinal ganglion cell axon guidance in the mouse optic chiasm: expression and function of Robos and Slits.\u00a0J Neurosci<\/i>\u00a020: 4975-82.\u00a0PMID: 10864955<\/a><\/p>\n List of publications from\u00a0PubMed<\/a><\/strong><\/p>\n","protected":false},"excerpt":{"rendered":"