William Lowry
email: BLOWRY@MCDB.UCLA.EDU
phone: 310-794-5175
fax: 310-794-9323
office: 451A BSRB
lab: 427A
homepage: http://www.lowrylab.com
Research Interests
1. 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. 2. Mechanisms of tumor initiation 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.
Selected Publications
Chin, M., Mason, M., Xie, W., Volinia, S., Singer, M., Peterson, C., Richter, L., Aimiuwu, O., Zhang, J., Khorovstov, I., Ott,V., Grunstein, M., Benvenisty, N., Croce, C., Clark, A., Baxter, T., Pyle, A., Teitell, M., Pellegrini, M., Plath, K., and Lowry, W.E.. 2009. Induced pluripotent stem cells and embryonic stem cells are distinguished by gene expression signatures Cell Stem Cell 5: 111-123 .
Karumbayaram, S., Novitch, B.G., Umbach, J.A., Richter, L., Lindgren, A., Conway, A., Clark, A., Goldman, S.A., Plath, K., Wiedau-Pazos, M., Kornblum, H.I., and Lowry, W.E.. 2009. Directed differentiation of human induced-pluripotent stem cells (iPS) generates active motor neurons Stem Cells 27: 806-811 .
Park, T.S., Galic, Z., Conway, A., Lindgren, A., Van Handel, B., Magnusson, M., Richter, L., Teitell, M.A., Mikkola, H., Lowry, W.E., Plath, K., and Clark, A.T.. 2009. Derivation of Primordial germ cells from Human Embryonic and Induced Pluripotent Stem Cells is significantly improved by co-culture with human fetal gonadal cells Stem Cells 27: 783-795 .
Lowry, W.E. and Plath, K.P.. 2008. The many ways to make an iPS cell Nature Biotechnology 26: 1246-1248 .
Wu, H., Kim, K.J., Mehta, K., Paxia, S., Sundstrom, A., Anantharaman, T., Kuraishy, A.I., Doan, T., Ghosh, J., Pyle, A.D., Clark, A., Lowry, W., Fan, G., Baxter, T., Mishra, B., Sun, Y., Teitell, M.A.. 2008. Copy Number Variant Analysis of Human Embryonic Stem Cells Stem Cells 26: 1484-1489 .
Lowry, W.E., Richter, L., Yachechko, R., Pyle, A.D., Tchieu, J., Sridharan, R., Clark, A.T., and Plath, K. 2008. Generation of human-induced pluripotent stem cells from dermal fibroblasts 2008 105: 2883-2888 .
Lowry, W.E. and Richter, L.. 2007. Signaling in adult stem cells Frontiers in Bioscience 12: 3911-3927 .
Blanpain, C., Lowry, W.E., Pasolli, H.A.,and Fuchs, E.. 2006. Canonical Notch Signaling Functions as a Commitment Switch in the Epidermal Lineage Genes and Development 20: 3022-3035 .
Lowry, W.E., Blanpain, C., Nowak, J., Guasch, G., Lewis, L., and Fuchs, E.. 2005. Defining the impact of beta-catenin/Tcf transactivation on epithelial stem cells Genes and Development 19: 1596-1611 .
Blanpain, C., Lowry, W.E., Geoghegan, A., Polak, L., and Fuchs, E.. 2004. Self-Renewal, Multipotency, and the Existence of Two Cell Populations within an Epithelial Stem Cell Niche Cell 118: 635-648 .