Research Interests
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.
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.
Biosketch
Training:
- 1988 B.A. Northwestern
University, Evanston, IL
- 1994 Ph.D. University
of California, Berkeley, California
Academic Positions:
- 1988-94 Dept.
of Molecular and Cell Biology
University of California at Berkeley
- 1994-2000 Postdoctoral
Fellow with Marc W. Kirschner, Professor and Chair
Dept. of Cell Biology, Harvard Medical School, Boston, MA
- 1998 Independent
consultant, Genetics Institute, Cambridge, MA
- 2000- Assistant
Professor, Washington University School of Medicine, Dept. of Molecular
Biology and Pharmacology
- 2007-Associate Professor, Washington University School of Medicine, Dept. of Molecular Biology and Pharmacology
Honors:
- 2007 Hope Award, American Cancer Society, Wash. U. School of Medicine
- 2006 American Cancer Society Research Scholar, Wash. U. School of Medicine
- 2000-02 Basil O'Connor Research Award, March of Dimes, Wash. U. School of Medicine
- 2000-02 Howard
Hughes Medical Institute, Faculty Development-Basic Research Award,
Wash. U. School of Medicine
- 1995-98 Postdoctoral
Fellowship, Cancer Research Fund of the Damon Runyon-Walter Winchell
Foundation, Harvard Medical School
- 1992 Teaching
Effectiveness Award, UC Berkeley
- 1992 Outstanding
Graduate Student Instructor, UC Berkeley 1988 Phi Beta
Kappa, Northwestern University
- 1987 Phi Eta
Sigma honorary society member, Northwestern University
- 1987 National
Science Foundation Undergraduate Research Fellowship, Northwestern
University
- 1986-87 Alice
G. Hough Scholarship, Northwestern University
Selected
Publications
For a listing of ALL publications through PubMed, click here.
He Z, Cai J, Lim JW, Kroll K, Ma L. A novel KRAB domain-containing zinc finger transcription factor ZNF431 directly represses Patched1 transcription. J Biol Chem. 2011 Mar 4;286(9):7279-89. Epub 2010 Dec 21.
Yellajoshyula D, Patterson ES, Elitt MS, Kroll KL. Geminin promotes neural fate acquisition of embryonic stem cells by maintaining chromatin in an accessible and hyperacetylated state. Proc Natl Acad Sci U S A. 2011 Feb 7.
Kristen L. Kroll. Geminin in embryonic development: coordinating transcription and the cell cycle during differentiation. [Frontiers in Bioscience 12, 1395-1409, January 1, 2007].
Seongjin Seo,
Kristen L. Kroll. Chromatin Connections that Regulate Transcription at the Transition
from Proliferation to Differentiation. [Cell Cycle 5:4, 374-380, 16 February 2006]; ©2006 Landes Bioscience.
Jennifer J. Taylor, Ting Wang, Kristen L. Kroll. Tcf- and Vent-binding sites regulate neural-specific geminin expression in the gastrula embryo. Dev Biol. 2006 Jan 15;289(2):494-506.
Aline Boos, Amy Lee, Dominic M. Thompson, Jr and Kristen L. Kroll. Subcellular translocation signals
regulate Geminin activity during embryonic development. Biol. Cell (2006) 98, 363–375 (Printed in Great Britain) doi:10.1042/BC20060007
Seo, S., Cook, G.A, and Kroll, K.L. (2004) The SWI/SNF chromatin remodeling protein Brg1 is required for neurogenesis and mediates transactivation of Ngn and NeuroD. Development, 132, pg. 105-115.
Postigo, A.A., Depp, J.L., Taylor, J.J., and Kroll, K.L. Regulation of Smad signaling through a differential recruitment of coactivators and corepressors by ZEB proteins. EMBO J. 2003 22 (10): 2453-2462.
Bainter J, Boos A, Kroll KL. Neural induction takes a transcriptional twist. Dev Dyn 2001 222: 315-327.
Kroll, K.L. and Kirschner, M.W. Easy Passage: Germline Transgenesis in Xenopus. Proc. Natl. Acad. Sci. USA 1999 96 (25): 14189-90.
Amaya, E. and Kroll, K. L. A Method for Generating Transgenic Frog Embryos. Methods in Molecular Biology 1999 97: 393-414.
Kroll KL, Salic AN, Evans LM, et al. Geminin, a neuralizing molecule that demarcates the future neural plate at the onset of gastrulation. Development 1998 125:3247-3258.
Enrique Amaya and Kristen L. Kroll. A method for generating transgenic frog embryos. Methods Mol Biol. 1999;97:393-414.
