Ken Cho, Ph.D.
4410 Nat Sci II
University of California Irvine
Irvine, CA 92697
Lab Tel: (949) 824-7950
Office Tel: (949) 824-4067
Gene Regulatory Networks Regulating Endoderm Development
A major unanswered question in biology is how differentiation of the myriad cell types of the adult body is hardwired in the genome. Using the frog as a model system, our goal is to elucidate the mechanisms controlling endoderm formation by combining experimental (e.g., ChIPseq and RNAseq) and computational approaches. Production of a thorough endodermal gene regulatory network in frog will provide a useful framework for prediction, that is applicable to early mouse and human embryogenesis, thereby offering valuable knowledge to the broader scientific community for reprogramming stem cells along endodermal cell lineages.
BMP Signaling in Preimplantation Mammalian Development
Using quantitative imaging techniques and analyses, we map and quantitate the dynamic activities of BMP signaling activities in preimplantation mouse embryos and demonstrate for the first time the biological function and mechanism of BMP signaling in the preimplantation mammalian embryos. We show that BMP signaling regulates cell division and is critical for the establishment of mouse blastocysts.Our work will shed light on an issue of early pregnancy loss: failure of the blastocyst to undergo normal development.
Genome engineering using the CRISPR/Cas9
The CRISPR/Cas9 system relies upon the formation of double-stranded hybrids between synthetic guide RNA and genomic DNA and confers mutations in the genome. With Xenopus, the ability to microinject hundreds of synchronous, in vitro-fertilized embryos represents a significant advantage over other systems for examining mutations in the F0 generation. We use Xenopus tropicalis and develop methods to eliminate a large genomic region and induce a homologous recombination at a desired locus within the genome.
- Owens, N.D.L. 1, Blitz, I.L. 1, Lane, M.A., Overton, J.D., Gilchrist, M.J#, Cho, K.W.Y#., Khokha, M.K. # (2016). Embryogenesis kinetics measured by high-resolution absolute quantitation of transcripts. Submitted. 1: co-first authros, # contributed equally. In press. Cell Reports.
- Chiang, M., Hallman, S., Cinquin, A., Reyes de Mochel, N., Paz, A., Kawauchi, S., Calof, A., Cho, KWY., Fowlkes, C.C., & Cinquin, O. (2015). Analysis of in vivo single cell behavior by high throughput, human-in-the-loop segmentation of three-dimensional images. BMC Bioinformatics. DOI 10.1186/s12859-015-0814-7
- Wang, X., Hsi, H., Guerrero-Juarez, CF., Pham, K., Cho, K., Monuki, ES, Cho, KWY., Gay, DL., Plikus, (2015). Principles and mechanisms of regeneration in the mouse model for wound-induced hair follicle neogenesis. Regeneration. doi: 10.1002/reg2.38.
- Reyes de Mochel, NS., Luong, M., Chiang, M., Javier, A.L., Luu, E., Cinquin, O., and Cho, KWY. (2015). BMP signaling regulates both cell proliferation and ICM lineage commitment in preimplantation-stage mouse embryos. Dev Biol. 397, 45-55.
- Yang, G., Yuan, G., Cho, K.W.Y., and Chen, Y. (2014). An atypical canonical BMP signaling pathway regulates Msx1 expression during odontogenesis. J Biol Chem. 289, 31492-31502.
- Chiu, WT., Le, R., Beisinger, J., Blitz, IL., Xie, X., Cho, KWY. (2014). Comprehensive genomic view of Foxh1 and Smad2/3 interaction in mesendoderm development. Development, 141, 4537-4547.
- Nakayama, T., Blitz I.L., Fish, M.B., Sumanth, A., Cho, K.W.Y., Grainger R. (2014). Cas9-based genome editing in Xenopus tropicalis. Methods in Enzymplogy, 546, 355-375.
- Yasuoka, Y., Suzuki, Y., Takahashi, S., Sudou, N., Haramoto, Y., Cho, KW., Asashima, M., Sugano, S., and Taira, M. (2014). Otx2 and TLE/Groucho occupancy marks tissue-specific cis-regulatory modules for head specification. Nature Communiations, 9:4322.
- Blitz, IL., Luong, M., Chu, W. and Cho, K.W. (2014). Application of genomic approaches to developmental biology (book chapter for Principal of Developmental Genetics, 2nd edition. Edited by Sally Moody). 37-48.
- Zheng, Z., Christley, S., Chiu, WT., Blitz, IL., Xie, X., Cho, KWY., Nie, Q. (2014) Inference of the Xenopus tropicalis embryonic regulatory network and spatial gene expression patterns. BMS Systems Biology. BMC Syst Biol. 8:3
- Blitz,IL., Biesinger, J., Xie, X., and Cho, KWY. (2013). Biallelic Genome Modification in F0 Xenopus tropicalis Embryos Using the CRISPR/Cas System. Genesis, 51:827-34.
- Doan, LT., Javier, A., Furr, NM., Nguyen, K., Cho, KW., and Monuki, ES. (2012). An ultrasensitive Bmp signaling reporter reveals that high Bmp signaling is not required for cortical hem fate. PLoS One. 7(9):e44009.
- Javier, A., Doran, L., Luong, M., Sun, A., Monuki, E., Cho KWY. (2012). Bmp indicator mice reveal dynamic regulation of transcriptional response. PLoS One. 7(9):e42566.
- Cho, KWY., Review on enhancers, Online Developmental Biology. (2012) DOI: 10.1002/wdev.53
- Alexander C, Zuniga E, Blitz IL, Wada N, Le Pabic P, Javidan Y, Zhang T, Cho KW, Crump JG, Schilling TF. 2011. Combinatorial roles for BMPs and Endothelin 1 in patterning the dorsal-ventral axis of the craniofacial skeleton. Development. 138:5135-46. PMID: 22031543.
- Onai, T. Blitz, I.L., Cho, K.W., and Holland, L.Z. (2010). Opposing Nodal/Vg1 and BMP signals mediate axial patterning in embryos of the basal chordate amphioxus. Dev Biol. 344:377-89.