Affiliations

Professor, Molecular, Cell, and Developmental Biology

Member, Cell & Developmental Biology GPB Home Area, Eli & Edythe Broad Center of Regenerative Medicine & Stem Cell Research, Gene Regulation GPB Home Area, JCCC Cancer and Stem Cell Biology Program Area, themes

Specification, Maintenance and Dysplasia of Epidermis The process by which cell fates are adopted and maintained in organisms has preoccupied much of biological investigation for a century. We seek to uncover the mechanisms by which cells interpret signals during development or in mature tissue and generate a response leading to cell fate specification, regulation of self-renewal and differentiation, or even aberrant proliferation. The epidermis and nervous system are derivatives of progenitors specified in embryonic ectoderm. While the study of lower organisms has elucidated aspects of this specification, there is still a great deal unknown with regards to cell fate decisions in mammalian ectoderm, particularly human. We have devised an experimental paradigm that allows for the isolation and molecular characterization of cells in a model of human ectodermal development. We expect to find both familiar and unfamiliar pathways related to these specification events, and that some of these pathways will be used again to maintain stem cells in mature epidermis. We are using both in vitro and in vivo models to study epidermal adult stem cell self-renewal and differentiation to confirm this hypothesis and to uncover novel mechanisms. Some of these pathways that regulate self-renewal and differentiation are also thought to be defective in degenerative or dysplastic diseases. Using a murine model for tumorigenesis in the epidermis, we employ powerful new technology to describe the molecular landscape underlying tumor initiation by stem cells, including whether misregulation of self-renewal and differentiation pathways plays a role in cancer.

White Andrew C, Tran Kathy, Khuu Joan, Dang Christine, Cui Yongyan, Binder Scott W, Lowry William E Defining the origins of Ras/p53-mediated squamous cell carcinoma. Proceedings of the National Academy of Sciences of the United States of America. 2011; 108(18): 7425-30. Plath Kathrin, Lowry William E Progress in understanding reprogramming to the induced pluripotent state. Nature reviews. Genetics. 2011; 12(4): 253-65. Patterson Michaela, Chan David N, Ha Iris, Case Dana, Cui Yongyan, Handel Ben Van, Mikkola Hanna Ka, Lowry William E Defining the nature of human pluripotent stem cell progeny. Cell research. 2011; . Lee Roger, Chang Sandy Y, Trinh Hung, Tu Yiping, White Andrew C, Davies Brandon S J, Bergo Martin O, Fong Loren G, Lowry William E, Young Stephen G Genetic studies on the functional relevance of the protein prenyltransferases in skin keratinocytes. Human molecular genetics. 2010; 19(8): 1603-17. Chin, M. H. Mason, M. J. Xie, W. Volinia, S. Singer, M. Peterson, C. Ambartsumyan, G. Aimiuwu, O. Richter, L. Zhang, J. Khvorostov, I. Ott, V. Grunstein, M. Lavon, N. Benvenisty, N. Croce, C. M. Clark, A. T. Baxter, T. Pyle, A. D. Teitell, M. A. Pelegrini, M. Plath, K. Lowry, W. E. Induced pluripotent stem cells and embryonic stem cells are distinguished by gene expression signatures. Cell Stem Cell. 2009; 5(1): 111-23. Karumbayaram Saravanan, Novitch Bennett G, Patterson Michaela, Umbach Joy A, Richter Laura, Lindgren Anne, Conway Anne E, Clark Amander T, Goldman Steve A, Plath Kathrin, Wiedau-Pazos Martina, Kornblum Harley I, Lowry William E Directed differentiation of human-induced pluripotent stem cells generates active motor neurons. Stem cells (Dayton, Ohio). 2009; 27(4): 806-11. Lowry, W. E. Richter, L. Yachechko, R. Pyle, A. D. Tchieu, J. Sridharan, R. Clark, A. T. Plath, K. Generation of human induced pluripotent stem cells from dermal fibroblasts. Proc Natl Acad Sci U S A. 2008; 105(8): 2883-8.