Research Interests

Embryonic patterning, epigenetic and transcriptional regulation, neurogenesis

Research Area

We are interested in understanding how embryonic and embryonic stem (ES) cells regulate self-renewal, lineage commitment, and differentiation and are studying these questions in the context of vertebrate neural development. Stepwise transcriptional cascades convert pluripotent embryonic cells into neurons: multipotent neural precursors form, commit to neuronal lineages, and then undergo cell cycle withdrawal and neuronal differentiation. We use ES, neural stem cell, and mouse models to study these processes.

Current Members

Kroll, Kristen L (Principal Investigator/Director)

Additional Information

A major focus of our work is on chromatin regulatory proteins, including the SWI-SNF and Polycomb complexes and the novel protein Geminin. These complexes critically regulate transcription to control self-renewal and differentiation in multiple cell contexts. They also regulate cell cycle progression and maintain genome integrity and their dysregulation is a pivotal aspect of multiple human malignancies. Our current efforts include: Transcriptional and epigenetic regulation of neural development and malignancy. We are: 1. determining how neural precursor-specific gene expression is transcriptionally regulated in early embryos and ES cells, 2. Characterizing roles for epigenetic regulators in controlling neural stem cell maintenance and differentiation, 3. Using cell-based screens to define new epigenetic regulators of these processes, and 4. Using mouse and cell-based models to assess how epigenetic regulation contributes to malignancy in medulloblastoma and glioma. Gem, SWI-SNF, and Polycomb interplay regulating transcription in embryonic and ES cells. We are defining how interactions between these complexes regulate transcription by defining direct transcriptional targets, composition of the protein complexes involved, and mechanisms of action at the chromatin level. We are also assessing how this is integrated with control of cell cycle progression and genome stability/euploidy, to determine how this occurs in normal cells and define its contributions to cancer progression.

Contact

Institution: Washington University

Web Page: http://devbio.wustl.edu/krolllab/index.html

Personal Phone: +44 1524 592058

General/Lab Phone: +44 1524 593192