Judith Kimble, PHD

Pubmed

More information:

• Dr. Kimble’s Lab webpage

Dr. Kimble is a Vilas Professor and Vannevar Bush Professor in Biochemistry.

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:

1.  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.
2. Shin, H., Haupt, K.A., Kershner, A.M., Kroll-Conner, P., Wickens, M. and J. Kimble (2017) SYGL-1 and LST-1 link niche signaling to PUF RNA repression for stem cell maintenance in Caenorhabditis elegans. PLOS Genetics 13(12), e1007121. PMCID:PMC5741267
3. Haupt, K.A, Law, K.T., Enright, A.L., Kanzler, C.R., Shin, H., Wickens, M., and J. Kimble (2019) A PUF hub drives self-renewal in C. elegans germline stem cells. Genetics 214(1), 147-161. PMCID:PMC6944405
4. Robinson-Thiewes, Sarah, Benjamin Dufour, Pier-Olivier Martel, Xavier Lechasseur, Amani Ange Danielle Brou, Vincent Roy2, Yunqing Chen, Judith Kimble & Patrick Narbonne (2021) Non autonomous regulation of germline stem cell proliferation by somatic MPK-1/MAPK activity in C. elegans. Cell Reports. 35, 109162. https://doi.org/10.1016/j.celrep.2021.109162
5. Lynch, T.R., Xue, M., Czerniak, C., Lee, C., and Kimble, J. (2022). “Notch-dependent DNA cis-regulatory elements and their dose-dependent control of C. elegans stem cell self-renewal” Development, 149, doi: 10.1242/dev.200332. PMID: 35394007