Associate Professor
Developmental Biology
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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 both mouse ES cells and mouse and Xenopus embryos to study these processes.
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 regulatory networks in neural development. We are: 1. identifying direct targets and regulatory enhancers used by several key bHLH transcription factors to regulate neuronal commitment, 2. determining how neural precursor-specific gene expression is transcriptionally regulated in early embryos and ES cells, and 3. Using genomic and function-based screens to isolate novel regulators of neurogenesis.
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.
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Research Publications
Kroll KL (2007 Jan 1). Geminin in embryonic development: coordinating transcription and the cell cycle during differentiation. Front Biosci. 12: 1395-409. Full Article >
Seo S, Kroll KL (2006 Feb). Geminin's double life: chromatin connections that regulate transcription at the transition from proliferation to differentiation. Cell Cycle. 5 (4): 374-9. Full Article >
Taylor JJ, Wang T, Kroll KL (2006 Jan 15). Tcf- and Vent-binding sites regulate neural-specific geminin expression in the gastrula embryo. Dev Biol. 289 (2): 494-506. Full Article >
Seo S, Herr A, Lim JW, Richardson GA, Richardson H, Kroll KL (2005 Jul 15). Geminin regulates neuronal differentiation by antagonizing Brg1 activity. Genes Dev. 19 (14): 1723-34. Full Article >
Seo S, Richardson GA, Kroll KL (2005 Jan). The SWI/SNF chromatin remodeling protein Brg1 is required for vertebrate neurogenesis and mediates transactivation of Ngn and NeuroD. Development. 132 (1): 105-15. Full Article >
Postigo AA, Depp JL, Taylor JJ, Kroll KL (2003 May 15). Regulation of Smad signaling through a differential recruitment of coactivators and corepressors by ZEB proteins. EMBO J. 22 (10): 2453-62. Full Article >
Contact Info
Kristen Kroll, Ph.D.
Office Location: 320 McDonnell Sciences Bldg.
Office Phone: (314)-362-7045
Lab Phone: (314)-747-5519
Campus Box: 8103
Fax: (314)-362-7058
kkroll@molecool.wustl.edu
http://molecool.wustl.edu/krolllab/
