DPLM Faculty Profiles — Dr. Scott Williams

Scott Williams, PhD

Scott E. Williams, PhD

Assistant Professor

Office: 919-966-2737

Email: scott_williams@med.unc.edu

C.V. (PDF)

Research Interests

The 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 "simple" 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, in utero 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.

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.

 

Williams figure 1

 

Selected Publications

Lough KJ, Byrd KM, Spitzer DC, and Williams SE (2017). Closing the gap: mouse models to study adhesion in secondary palatogenesis. J Dent Res [Special Issue on Orofacial Clefting, Craniofacial and Dental Anomalies] Available online August 17, 2017.  PMID: 28817360

Byrd KM, Lough KJ, Patel JH, Descovich CP, Curtis TA and Williams SE (2016). LGN plays distinct roles in oral epithelial stratification, filiform papilla morphogenesis and hair follicle development. Development 143(15): 2803-17. PMID: 27317810  [Selected for Cover, F1000 reviewed]

Williams SE*, Garcia I, Crowther AJ, Stewart A, Li S, Stewart A, Liu H, Lough, KJ, O’Neill S, Veleta K, Oyarzabal EA, Merrill JR, Shi YI and Gershon TR* (2015). Aspm sustains postnatal cerebellar neurogenesis and medulloblastoma growth in mice. Development 142(22): 3921-32. PMID: 26450969 *co-corresponding authors

Williams SE, Ratliff LA, Postiglione MP, Knoblich JA and Fuchs E (2014). Par3-mInsc and Gai3 cooperate to promote oriented epidermal cell divisions through LGN. Nat Cell Biol 16(8): 758-69. PMID: 25016959 [F1000 reviewed]

Williams SE and Fuchs E (2013). Oriented divisions, fate decisions. Curr Opin Cell Biol 25(6):749–758. PMID: 24021274

Williams SE, Beronja S, Pasolli HA and Fuchs E (2011). Asymmetric cell divisions promote Notch-dependent epidermal differentiation. Nature 470: 353-358.  PMID: 21331036 [Comment in Nat Rev Genetics 12: 226; F1000 reviewed].

Ezratty E, Stokes N, Chai S, Shah A, Williams SE and Fuchs E (2011). A role for the primary cilium in Notch signaling and epidermal differentiation during skin development. Cell 45: 1129-41.  PMID: 21703454

Luxenburg C, Pasolli HA, Williams SE and Fuchs E (2011). Developmental roles for Srf, cortical cytoskeleton and cell shape in epidermal spindle orientation. Nat Cell Biol 13: 203-14. PMID: 21336301 [F1000 reviewed] 

Beronja S, Livshits G, Williams SE and Fuchs E (2010). Rapid functional dissection of genetic networks via tissue-specific transduction and RNAi in mouse embryos. Nat Med 16: 821-7.   PMID: 20526348

Perez-Moreno M, Song W, Pasolli HA, Williams SE and Fuchs E (2008). Loss of p120 catenin and links to mitotic alterations, inflammation and skin cancer. PNAS 105: 15399-404.  PMID: 18809907 [F1000 reviewed]

Williams SE, Grumet M, Colman DR, Henkemeyer M, Mason CA, and Sakurai T (2006). A role for Nr-CAM in the patterning of binocular visual pathways. Neuron 50: 535-47.  PMID: 16701205 [Comment in Neuron 50: 519-21]

Williams SE, Mason CA, and Herrera E (2004). The optic chiasm as a midline choice point. Curr Opin Neurobiol 14: 51-60.  PMID: 15018938

Williams SE, 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. Neuron 39: 919-935.  PMID: 12971893 [Comment in Neuron 39: 885-8; F1000 reviewed]

Erskine L, Williams SE, 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. J Neurosci 20: 4975-82.  PMID: 10864955


View list of publications from
PubMed

PubMed Articles
LGN plays distinct roles in oral epithelial stratification, filiform papilla morphogenesis and hair follicle development.
Related Articles

LGN plays distinct roles in oral epithelial stratification, filiform papilla morphogenesis and hair follicle development.

Development. 2016 Aug 01;143(15):2803-17

Authors: Byrd KM, Lough KJ, Patel JH, Descovich CP, Curtis TA, Williams SE

Abstract
Oral epithelia protect against constant challenges by bacteria, viruses, toxins and injury while also contributing to the formation of ectodermal appendages such as teeth, salivary glands and lingual papillae. Despite increasing evidence that differentiation pathway genes are frequently mutated in oral cancers, comparatively little is known about the mechanisms that regulate normal oral epithelial development. Here, we characterize oral epithelial stratification and describe multiple distinct functions for the mitotic spindle orientation gene LGN (Gpsm2) in promoting differentiation and tissue patterning in the mouse oral cavity. Similar to its function in epidermis, apically localized LGN directs perpendicular divisions that promote stratification of the palatal, buccogingival and ventral tongue epithelia. Surprisingly, however, in dorsal tongue LGN is predominantly localized basally, circumferentially or bilaterally and promotes planar divisions. Loss of LGN disrupts the organization and morphogenesis of filiform papillae but appears to be dispensable for embryonic hair follicle development. Thus, LGN has crucial tissue-specific functions in patterning surface ectoderm and its appendages by controlling division orientation.

PMID: 27317810 [PubMed - indexed for MEDLINE]

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