The Kimble Laboratory
Faculty > Judith Kimble
Judith Kimble
Vilas Professor, Department of Biochemistry; Investigator, Howard Hughes Medical Institute
jekimble@facstaff.wisc.edu
Research Description
Our lab focuses on the regulation of germline stem cells (GSCs) in the nematode Caenorhabditis elegans. We identified the stem cell niche for these GSCs in 1981. During the next decade, we contributed to delineation of the Notch signaling pathway and showed that our niche uses Notch signaling to maintain GSCs. More recently we have analyzed the regulatory network that acts downstream of Notch signaling to maintain germ cells in a stem cell state or to drive them into differentiation.
FBF provides the major hub of the network controling stem cell maintenance. FBF is a conserved RNA-binding protein of the PUF (for Pumilio and FBF) family; PUF proteins are also essential in Drosophila for GSC maintenance and in planaria for maintenance of neoblasts, which are the stem cells required for their remarkable regenerative capacity. PUF proteins are also enriched in human embryonic stem cells (hESCs) and in human GSCs. We showed in collaboration with the Thomson lab here at UW-Madision that PUF proteins regulate ERK mRNA in both C. elegans GSCs and hESCs. More recently, we examined FBF at a genomic level, a study that revealed FBF to be a broad-spectrum regulator of differentiation with many target mRNAs shared with its human PUF counterparts.
Our lab is currently working on identifying new Notch targets that are essential for stem cells in addition to projects aimed to understand how the regulatory network transitions from a stem cell state to a differentiated state.
Selected References
Cinquin, O., Crittenden, S.L., Morgan, D.E. and J. Kimble (2010) Progression from a stem cell-like state to early differentiation in the C. elegans germ line. PNAS 107, 2048-2053.
Kershner, A. and J. Kimble (2010) Genome-wide analysis of mRNA targets for Caenorhabditis elegans FBF, a conserved stem cell regulator. PNAS 107, 3936-3941.
Jeong, J., Verheyden, J.M. and J. Kimble (2011) Cyclin E and Cdk2 control GLD-1, the mitosis/meiosis decision, and germline stem cells in Caenorhabditis elegans. PLoS Genetics 7(3), e1001348.
Friend, K., Campbell, Z.T., Cooke, A., Kroll-Conner, P., Wickens, M.P. and J. Kimble (2012) A conserved PUF/Ago/eEF1A complex attenuates translation elongation. Nature Structural and Molecular Biology 19(2), 176-183.