DPLM Faculty Profiles — Dr. Scott Williams

Scott Williams, PhD

Scott E. Williams, PhD

Assistant Professor

Office: 919-966-2737

E-mail: scott_williams@med.unc.edu

C.V. (PDF)

Research Interests

The mammalian skin epithelium 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. 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, 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.


Williams figure 1


Selected Publications

Williams SE, Beronja S, Pasolli HA and Fuchs E (2011). Asymmetric cell divisions promote Notch-dependent epidermal differentiation. Nature 470: 353-358. [Pubmed]

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. [Pubmed]

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 [Pubmed]

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. [Pubmed]

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. [Pubmed]

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. [Pubmed]

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

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. [Pubmed]

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. [Pubmed]

View list of publications from

PubMed Articles
Aspm sustains postnatal cerebellar neurogenesis and medulloblastoma growth.
Related Articles

Aspm sustains postnatal cerebellar neurogenesis and medulloblastoma growth.

Development. 2015 Oct 8;

Authors: Williams SE, Garcia I, Crowther AJ, Li S, Stewart A, Liu H, Lough KJ, O'Neill S, Veleta K, Oyarzabal EA, Merrill JR, Shih YI, Gershon TR

Alterations in genes that regulate brain size may contribute to both microcephaly and brain tumor formation. Here, we report that Aspm, a gene that is mutated in familial microcephaly, regulates postnatal neurogenesis in the cerebellum and supports the growth of medulloblastoma, the most common malignant pediatric brain tumor. Cerebellar granule neuron progenitors (CGNPs) express Aspm when maintained in a proliferative state by Sonic Hedgehog (Shh) signaling, and Aspm is expressed in Shh-driven medulloblastoma in mice. Genetic deletion of Aspm reduces cerebellar growth, while paradoxically increasing the mitotic rate of CGNPs. Aspm-deficient CGNPs show impaired mitotic progression, altered patterns of division orientation and differentiation, and increased DNA damage, which causes progenitor attrition through apoptosis. Deletion of Aspm in mice with Smo-induced medulloblastoma reduces tumor growth while increasing DNA damage. Co-deletion of Aspm and either of the apoptosis regulators Bax or Trp53 (p53) rescues the survival of neural progenitors and reduces the growth restriction imposed by Aspm deletion. Our data show that Aspm functions to regulate mitosis and to mitigate DNA damage during CGNP cell division, causes microcephaly through progenitor apoptosis when mutated, and sustains tumor growth in medulloblastoma.

PMID: 26450969 [PubMed - as supplied by publisher]