Area of Interest
I have a longstanding interest in cell and developmental biology, spanning a scientific career that began as a cell therapy and stem cell researcher at a biotechnology company, continuing through a doctorate on retinal axon guidance, and culminating in my postdoctoral research on asymmetric cell divisions (ACDs) and epidermal differentiation. Here at UNC, I will investigate the mechanisms that control oriented cell divisions in the epidermis and other stratified epithelia, with a particular interest in the oral epithelia. My objectives will be twofold: 1) to identify the genes and pathways that regulate spindle orientation and epithelial differentiation during development, and 2) to determine whether these pathways—particularly with respect to how they alter tissue polarity—influence squamous tumor progression. Specifically, I aim to identify novel components of the apical polarity and spindle orientation complex; determine the factors that dictate whether a given progenitor divides symmetrically or asymmetrically; characterize cell fate determinants (including those in the Notch pathway) that are segregated during ACDs; and determine the relative contribution that ACDs and other epithelial differentiation mechanisms play during development, homeostasis and cancer. I plan to use an extremely versatile genetic tool I helped develop as a post-doc—in utero ultrasound-guided microinjection of lentiviruses harboring shRNAs or cDNAs—to rapidly and comprehensively tackle these problems. This powerful technique endows the mouse with genetic manipulability previously only possible in invertebrate models. Perhaps more importantly, this method provides rich fodder for both exploration and collaboration, as it can be applied to the study of virtually any cell type where the virus can be delivered.
Williams SE, Beronja S, Pasolli HA and Fuchs E (2011). Asymmetric cell divisions promote Notch-dependent epidermal differentiation.Nature 470: 353-358.
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.
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 .
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.
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.
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.
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.
Awards and Honors
National Merit Scholarship, 1992-1996
American Cancer Society Postdoctoral Fellow, 2007-2010
EACR Poster Prize Winner, Cell Cycle, Cancer & Development Conference, 2011
ATIP-Avenir Pathway to Independence Awardee, INSERM-CNRS, 2012