Judith Kimble, Phd
Vilas Professor, Biochemistry and Investigator, Howard Hughes Medical Institute
341E Biochemistry Addition
433 Babcock Drive
Our lab focuses on germline stem cells (GSCs) and their regulation in the nematode C. elegans. GSCs reside within a stem cell niche and generate daughter cells that differentiate. This niche uses Notch signaling to maintain a pool of GSCs that divide stochastically. Notch signaling activates a regulatory network to maintain germ cells in a stem cell state or to drive them into differentiation. The two key target genes that are activated in GSCs by Notch signaling encode novel proteins that are predicted to be largely disordered. These two genes form a functional link between Notch signaling and the regulatory network that acts in stem cells to maintain totipotency or promote differentiation. The major hub of that network for GSC maintenance relies on FBF, a sequence-specific RNA binding protein of the broadly conserved PUF family maintenance. The major hub for GSC differentiation relies on GLD proteins, which are also RNA regulators. FBF targets >1000 mRNAs, about a quarter of which are shared with its human PUF counterparts. We continue to analyze regulators of stem cell maintenance, regulators of differentiation as sperm or oocyte and the molecular network that encompasses both stem maintenance and differentiation.
Honors & Awards
- Chair, President’s Committee on National Medal of Science, 2015-2017
- President, Society for Developmental Biology, 2004-2005
- Hilldale Award, Biological Sciences Division, 2003
- American Philosophical Society, elected in 2002
- Vilas Professorship, 2001
- National Academy of Sciences, elected in 1995
- Lee, C., Sorensen, E.B., Lynch, T.R. and J. Kimble (2016) C. elegans GLP-1/Notch activates transcription in a probability gradient across the germline stem cell pool. eLife 5, e18370.
- Aoki, S.T., Kershner, A.M., Bingman, C.A., Wickens, M. and J. Kimble (2016) PGL germ granule assembly protein is a base-specific, single-stranded RNase. Proc Natl Acad Sci USA 113(5): 1279-1284.
- Prasad, A., Porter, D.F., Kroll-Conner, P.L., Mohanty, I., Ryan, A.R., Crittenden, S.L., Wickens, M. and J. Kimble (2016) The PUF binding landscape in metazoan germ cells. RNA 22(7), 1026-1043.
- Noble, D.C, Aoki, S.T., Ortiz, M.A., Kim, K.W., Verheyden, J.M. and J. Kimble (2016) Genomic analyses of sperm fate regulator targets reveal a common set of oogenic mRNAs in Caenorhabditis elegans. Genetics 202(1), 221-234.
- Seidel, H.S. and J. Kimble (2015) Cell-cycle quiescence maintains Caenorhabditis elegans germline stem cells independent of GLP-1/Notch. eLife 4, 10832.
- Kershner, A.M., Shin, H., Hansen, T.J. and J. Kimble (2014) Discovery of two GLP-1/Notch target genes that account for the role of GLP-1/Notch signaling in stem cell maintenance. PNAS111(10), 3739-3744