Pathology & Lab Medicine
Cancer Cell Biology
Area of interest
Tissue development, homeostasis and regeneration depend on the precise coordination of self-renewal and differentiation programs. A critical point of regulation of this balance is at the level of cell division. Stem and progenitor cells can divide symmetrically to favor self-renewal or asymmetrically to promote differentiation. In the epidermis and other stratified epithelia, we have shown that the spatial orientation of the plane of cell division can dictate specific fate outcomes. Moreover, disruption of the normal balance of symmetric and asymmetric divisions during development can result in lethal differentiation defects. During homeostasis, asymmetric cell divisions (ACDs) maintain a stable pool of stem cells that can be used to sustain tissue growth, or mobilized in response to injury. However, dysregulation of this machinery can lead to cancer, particularly in epithelia where tissue turnover is rapid and continuous. The overarching goal of my lab is to discover the molecular mechanisms that control the balance between self-renewing and differentiate divisions during development, homeostasis, wound healing, and diseases such as cancer, using the skin and oral epithelia as model systems. Under this broad umbrella, our research focuses on four specific areas:
- Intrinsic and extrinsic mechanisms that control oriented cell divisions during development
- Oral stem cells and their function during homeostasis and regeneration
- Mechanisms that drive oral cancer progression through altering the balance between symmetric and asymmetric divisions, and
- Role of cell adhesion proteins in the developmental disorder cleft palate
I strive to establish a research program that is innovative and cross-disciplinary, with a central theme of understanding how oriented cell divisions function in stratified epithelia, but with broad approaches that touch on developmental, stem cell, and cancer biology.
Closing the gap: mouse models to study adhesion in secondary palatogenesis.
Lough KJ, Byrd KM, Spitzer DC, and Williams SE. J Dent Res (2017) 96(11):1210-1220. PMID: 28817360. [Special Issue on Orofacial Clefting, Craniofacial and Dental Anomalies]
LGN plays distinct roles in oral epithelial stratification, filiform papilla morphogenesis and hair follicle development.
Byrd KM, Lough KJ, Patel JH, Descovich CP, Curtis TA and Williams SE. Development (2016) 143(15): 2803-17. PMID: 27317810. [Selected for Cover, F1000 reviewed]
Aspm sustains postnatal cerebellar neurogenesis and medulloblastoma growth in mice.
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*. Development (2015) 142(22): 3921-32. PMID: 26450969. *co-corresponding authors.
Par3-mInsc and Gai3 cooperate to promote oriented epidermal cell divisions through LGN.
Williams SE, Ratliff LA, Postiglione MP, Knoblich JA and Fuchs E. Nat Cell Biol (2014) 16(8): 758-69. PMID: 25016959. [F1000 reviewed]
Oriented divisions, fate decisions.
Williams SE and Fuchs E. Curr Opin Cell Biol (2013) 25(6):749–758. PMID: 24021274
Asymmetric cell divisions promote Notch-dependent epidermal differentiation.
Williams SE, Beronja S, Pasolli HA and Fuchs E (2011). Nature 470: 353-358.
A role for the primary cilium in Notch signaling and epidermal differentiation during skin development.
Ezratty E, Stokes N, Chai S, Shah A, Williams SE and Fuchs E (2011). Cell 45: 1129-41.
Developmental roles for Srf, cortical cytoskeleton and cell shape in epidermal spindle orientation.
Luxenburg C, Pasolli HA, Williams SE and Fuchs E (2011). Nat Cell Biol 13: 203-14 .
Rapid functional dissection of genetic networks via tissue-specific transduction and RNAi in mouse embryos.
Beronja S, Livshits G, Williams SE and Fuchs E (2010). Nat Med 16: 821-7.
Loss of p120 catenin and links to mitotic alterations, inflammation and skin cancer.
Perez-Moreno M, Song W, Pasolli HA, Williams SE and Fuchs E (2008). PNAS 105: 15399-404.
A role for Nr-CAM in the patterning of binocular visual pathways.
Williams SE, Grumet M, Colman DR, Henkemeyer M, Mason CA, and Sakurai T (2006). Neuron 50: 535-47.
Ephrin-B2 and EphB1 mediate retinal axon divergence at the optic chiasm.
Williams SE, Mann F, Sakurai T, Erskine L, Wei S, Rossi DJ, Gale N, Holt CE, Mason CA, and Henkemeyer M (2003). Neuron 39: 919-935
Awards and Honors
- Joe W. Grisham Award for Excellence in Graduate Student Teaching, Department of Pathology
Kimmel Scholar Award