Judith Kimble, PHD
Position title: Professor, Biochemistry
Dr. Kimble is a Vilas Professor and Vannevar Bush Professor in Biochemistry.
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.
- 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. PNAS 111(10), 3739-3744.
- Seidel, H.S. and J. Kimble (2015) Cell-cycle quiescence maintains Caenorhabditis elegans germline stem cells independent of GLP-1/Notch. eLife 4, 10832.
- 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.
- Aoki, S.T., Porter, D.F., Prasad, A., Wickens, M., Bingman, C.A., and J. Kimble (2018) An RNA-binding multimer specifies nematode sperm fate. Cell Reports 23(13), 3769-3775.
- Lee, C., Shin, H and J. Kimble (2019) Dynamics of Notch-dependent transcriptional bursting in its native context. Developmental Cell (in press)