Kristen Kroll, PhD

Research interests

Developmental, Regenerative, and Stem Cell Biology Program, Molecular Cell Biology Program

Our research focuses on defining gene regulatory networks (GRNs) that control neural cell specification, neurogenesis, and the generation of specific neuronal cell types. We are particularly interested in understanding how epigenetic regulation modulates these networks and how their dysregulation contributes to neurodevelopmental disorders and birth defects, including epilepsy, autism spectrum disorder, and neural tube defects. This work uses directed differentiation of human pluripotent stem cells (embryonic stem cells and induced pluripotent stem cells), mouse models, and a wide range of cellular, molecular, and genomic approaches, to define roles for transcriptional and epigenetic regulation in shaping developmental transitions.

To learn more about our research, visit https://sites.wustl.edu/krolllab/research/

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

2021-Professor, Washington University School of Medicine, Department of Developmental Biology

Selected publications

Lewis E. M. A., Chapman G., Kaushik K., Determan J., Antony I., Meganathan K., Narasimhan M., Gontarz P., Zhang B., and Kroll K. L. (2022). Regulation of human cortical interneuron development by the chromatin remodeling protein CHD2. Scientific reports, 12(1), 1-18. https://doi.org/10.1038/s41598-022-19654-y

Kfoury-Beaumont N, Prakasam R, Pondugula S, Lagas JS, Matkovich S, Gontarz P, Yang L, Yano H, Kim AH, Rubin JB, Kroll KL. The H3K27M mutation alters stem cell growth, epigenetic regulation, and differentiation potential. BMC Biol. 2022 May 30;20(1):124. doi: 10.1186/s12915-022-01324-0. PubMed PMID: 35637482; PubMed Central PMCID: PMC9153095.

Meganathan K, Prakasam R, Kaushik K, Chapman G, Antony I, Kroll KL. Derivation of cortical interneurons from human pluripotent stem cells to model neurodevelopmental disorders. In: Buttermore E, editor. Phenotyping of Human iPSC-derived Neurons: Patient-Driven Research 1 ed. Amsterdam, Netherlands: Elsevier; 2022. Chapter 9; p.33.

Chapman G, Antony I, Narasimhan M, Shen R, Elman R, Kroll KL. Cellular and Molecular Neurobiology of Autism Spectrum Disorder. In: Kana R, editor. The Neuroscience of Autism Amsterdam, Netherlands: Elsevier; 2022. Chapter 10; p.30.

Meganathan K, Prakasam R, Baldridge D, Gontarz P, Zhang B, Urano F, Bonni A, Constantino JN, Kroll KL. Alterations in neuronal physiology, development, and function associated with a common duplication of chromosome 15 involving CHRNA7. bioRxiv. Forthcoming; https://doi.org/10.1101/2020.01.28.922187.

Anderson NC, Chen PF, Meganathan K, Afshar Saber W, Bhattacharyya A, Kroll K, and Sabin M on behalf of the Cross-IDDRC Human Stem Cell Working Group. Balancing Serendipity and Reproducibility: Pluripotent stem cells as experimental systems for intellectual and developmental disorders.Stem Cell Reports. https://doi.org/10.1016/j.stemcr.2021.03.025

Emily M. A. Lewisa, Komal Kaushika, Luke A. Sandovala, Irene Antonya, Sabine Dietmanna, Kristen L. Krolla* Epigenetic regulation during human cortical development: seq-ing answers from the brain to the organoid. https://doi.org/10.1016/j.neuint.2021.105039

“New models to understand the intricacies of neurodevelopmental disorders”. Scientia. https://doi.org/10.33548/SCIENTIA663

Lewis, EMA, Sankar, S, Tong, C, Patterson, ES, Waller, LE, Gontarz, P, Zhang, B, Ornitz, DM, Kroll, KL. Geminin is required for Hox gene regulation to pattern the developing limb. Developmental Biology (2020), https://doi.org/10.1016/j.ydbio.2020.05.007

Lewis, E.M.A.*, Meganathan, K.*, Baldridge, D., Gontarz, P., Zhang, B., Bonni, A., Constantino, J., and Kroll, K.L. Cellular and molecular characterization of multiplex autism in human induced pluripotent stem cell-derived neurons. Molecular Autism, 2019, 10(51) doi:10.1186/s13229-019-0306-0. PMC6936127.

*Authors contributed equally to this work.

Meganathan, K., Prakasam, R., and Kroll, K.L. A translational rheostat integrates euchromatin regulation and growth of pluripotent embryonic cells. Stem Cell Investigation; 2019, 6(11). http://PMC6556695.

Lewis, E.M.A., and Kroll, K.L. Development and disease in a dish: the epigenetics of neurodevelopmental disorders. Epigenomics, 2018; 10(2):219-231. PMC5810842.

Meganathan, K, Lewis, E.M.A., Gontarz, P., Liu, S., Stanley, E.G., Elefanty, A.G., Huettner, J.E., Zhang, B., and Kroll, K.L. Regulatory networks specifying cortical interneurons from human embryonic stem cells reveal roles for CHD2 in interneuron development. Proceedings of the National Academy of Science, 2017; 114(52):E11180–E11189. PMC5748186.

Sankar, S., Patterson, E., Lewis, E.M.A., Waller, L.E., Tong, C., Dearborn, J., Wozniak, D., Rubin, J.B., and Kroll, K.L.. Geminin deficiency enhances survival in a murine medulloblastoma model by inducing apoptosis of preneoplastic granule neuron precursors. Genes & Cancer, 2017; 8(9-10):725-744. PMC5724806.

Sankar, S., Yellajoshyula, D., Zhang, B., Teets, B., Rockweiler, N., and Kroll, K.L. Gene regulatory networks in neural cell fate acquisition from genome-wide chromatin association of Geminin and Zic1. Scientific Reports, 2016; 6:37412. PMC5121602.

Dandulakis, M.G., Meganathan, K., Kroll, K.L., Bonni, A., and Constantino, J.N. Complexities of X chromosome inactivation status in female human induced pluripotent stem cells-a brief review and scientific update for autism research. Journal of neurodevelopmental disorders. 2016; 8:22. PMC4907282.

Corley, M. and Kroll, K.L. The roles and regulation of Polycomb complexes in neural development.  Cell and Tissue Research (2015), 359(1):65-85. [In the Special Issue: How to build a neuron – the problem of generic neuronal differentiation.] PMC4286515

Patterson, E.S, Waller, L.E., and Kroll, K.L.  Geminin loss causes neural tube defects through disrupted progenitor specification and neuronal differentiation. Developmental Biology (2014) Sep 1;393(1):44-56 PMID: 24995796. PMC4134736

Caronna, E., Patterson, E.S., Hummert, and Kroll, K.L. Geminin restrains mesendodermal fate acquisition of mouse embryonic stem cells and is associated with antagonism of Wnt signaling and enhanced Polycomb-mediated repression. Stem Cells, (2013) 31:1477-87. PMID: 23630199. PMC3776023

Siles, L., Lim, J., Sanchez-Tillo, E., Lim, J.W., Darling, D.S., Kroll, K.L., and Postigo, A.  ZEB1 imposes a temporary stage-dependent inhibition of muscle gene expression and differentiation via CtBP-mediated transcriptional repression. Molecular and Cellular Biology (2013), 33(7): 1368-82. PMC3624276

Yellajoshyula, D., Lim, J., Thompson, D.M., Witt, J.S., Patterson, E.S., and Kroll, K.L. Geminin regulates the transcriptional and epigenetic status of neuronal fate promoting genes during mammalian neurogenesis. Molecular and Cellular Biology (2012), 00737-12,  PMC3486176.

Sengupta, R., Dubuc, A., Ward, S., Yang, L., Northcott, P., Woerner, B., Kroll, K., Luo, J., Taylor, M., Wechsler-Reya, R., and Rubin, J.  Cxcr4 Activation Defines a New Subgroup of Sonic Hedgehog-Driven Medulloblastoma. Cancer Research (2012) 72(1): 122-32. PMC3520097

Ishibashi, S., Kroll, K.L., and Amaya, E. Generating Transgenic Frog Embryos by Restriction Enzyme Mediated Integration. Methods in Molecular Biology (2012) 917: pgs. 185-203. PMC3818119

Yellajoshyula, D., Patterson, E.S., Elitt, M.S. and Kroll, K.L.  Geminin promotes neural fate acquisition of embryonic stem cells by maintaining chromatin in an accessible and hyperacetylated state.  Proc. Natl. Acad. of Sciences  (2011) 108(8):3294-9. PMC3044367

He, Z., Cai, J., Lim, J., Kroll, K. and Ma, L.  A novel KRAB domain-containing Zinc-finger transcription factor ZNF431 directly represses Patched1 transcription. Journal of Biological Chemistry  (2011) 286 (9): 7279-89. PMID: 21177534. PMC3044984

Lim, J., Hummert, P., Mills, J.C. and Kroll, K.L. Geminin cooperates with Polycomb to restrain multi-lineage commitment in the early embryo.  Development (2011) 138 (1): 33-44. PMC2998164. 

Amaya, E. and Kroll, K. Production of transgenic Xenopus laevis by restriction enzyme mediated integration and nuclear transplantation. J. Vis. Exp. 2010, 42, Aug21, doi: 10.3791/2010. PMC3156005

Langer, E.M., Feng, Y. Zhaoyuan, H., Rauscher, F.J., Kroll, K.L., and Longmore, G. D. Ajuba LIM proteins are Snail corepressors required for neural crest development. Developmental Cell, 2008, 14(3): 424-36. PMC2279146

Ishibashi S., Kroll K.L., and Amaya E. A method for generating transgenic frog embryos. Methods in Molecular Biology 2008. 461, pg. 447-66. PMC3814177

Seo, S., Lim, J., Yellajoshyula, D., Chang, L., and Kroll, K.L.  Neurogenin and NeuroD direct transcriptional targets and their regulatory enhancers EMBO J 2007, 26 (24): 5093-108. PMC2140110

Yellajoshyula, D., Patterson, E., and Kroll, K.L.  Maternal cyclin B levels “Chk” the onset of DNA replication checkpoint control in Drosophila.  Bioessays 2007 Oct 29(10):  949-52. PMID: 17876773

Lauberth, S.M., Bilyeu, A.C., Firulli, B.A., Kroll, K.L., Rauchman, M. A phosphomimetic mutation in the sall1 repression motif disrupts recruitment of the nucleosome remodeling and deacetylase complex and repression of Gbx2. J Biol Chem. 2007 282 (48):  34858-68. PMID: 17895244.

Ishibashi, Sl., Kroll, K.L., and Amaya, E. (2007) Generation of transgenic Xenopus laevis. I. High-Speed Preparation of Egg Extracts CSH Protocols; September, 2007; doi:10.1101/pdb.prot4838

Ishibashi, Sl., Kroll, K.L., and Amaya, E. (2007) Generation of transgenic Xenopus laevis. II. Sperm Nuclei Preparation CSH Protocols; September, 2007; doi:10.1101/pdb.prot4839

Ishibashi, Sl., Kroll, K.L., and Amaya, E. (2007) Generation of transgenic Xenopus laevis. III. Sperm Nuclear Transplantation. CSH Protocols; September, 2007; doi:10.1101/pdb.prot4840

Kroll, K.L.  (2007) Geminin in embryonic development:  coordinating transcription and the cell cycle during differentiation. Frontiers in Bioscience 12, 1395-1409. PMID: 17127390

Seo, S. and Kroll, K.L.  (2006)  Geminin’s double life:  chromatin connections that regulate the transition from proliferation to differentiation. Cell Cycle, 5 (4), 374-9. PMID: 16479171

Taylor, J., Wang, T., and Kroll, K.L. (2006) Tcf- and Vent-binding sites regulate neural-specific geminin expression in the gastrula embryo. Developmental Biology 289 (2), pg. 494-506.  PMID: 16337935

Boos, A., Lee, A., Thompson, D.M., and Kroll, K.L. (2006) Subcellular translocation signals regulate Geminin activity during embryonic development. Biol. Cell. 98 (6), 363-75. PMID: 16464175

Seo, S., Herr, A., Lim, J., Richardson, G., Richardson, H., and Kroll, K.L.  (2005) Geminin regulates neuronal differentiation by antagonizing Brg1 activity.  
Genes and Development 19 (14), 1723-34.  PMID: 16024661. PMCID: PMC1176010

Concurrent commentary on Seo et al., 2005:  
Aigner, S. and Gage, F.H.  (2005) A small Gem with great powers:  Geminin keeps neural progenitors thriving.  Developmental Cell 9, pg. 171-72. PMID: 16054024.

Seo, S., Cook, G.A, and Kroll, K.L. (2005) The SWI/SNF chromatin remodeling protein Brg1 is required for neurogenesis and mediates transactivation of Ngn and NeuroD. Development 132, 105-115. PMID: 15576411

See a complete list of Dr. Kroll’s publications »