- Wnt/β-catenin signaling in development and cancer
- Cancer-related gene regulation
- Developmental Biology and Gene Regulation
- Congenital heart defects research
- Pluripotent Stem Cells Research
- Hippo pathway signaling and YAP/TAZ
- Epigenetics and DNA Methylation
- Ubiquitin and proteasome pathways
- RNA Research and Splicing
- Genetics and Neurodevelopmental Disorders
- Zebrafish Biomedical Research Applications
- Tissue Engineering and Regenerative Medicine
- Hedgehog Signaling Pathway Studies
- Erythrocyte Function and Pathophysiology
- Renal and related cancers
- Animal Genetics and Reproduction
- Kruppel-like factors research
- Pancreatic function and diabetes
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Axon Guidance and Neuronal Signaling
- RNA Interference and Gene Delivery
- Nerve injury and regeneration
- HER2/EGFR in Cancer Research
- RNA modifications and cancer
- Neurobiology and Insect Physiology Research
University of Washington
2011-2021
Howard Hughes Medical Institute
2010-2021
Auburn University
2021
California Institute for Regenerative Medicine
2012-2017
American Association For The Advancement of Science
2009-2016
Seattle University
1999-2012
Harvard University
1998-2011
Brigham and Women's Hospital
2011
University of Crete
2011
Huazhong University of Science and Technology
2011
The serine/threonine kinase Xgsk-3 and the intracellular protein beta-catenin are necessary for establishment of dorsal-ventral axis in Xenopus. Although genetic evidence from Drosophila indicates that is upstream beta-catenin, direct interactions between these proteins have not been demonstrated. We demonstrate phosphorylation vivo requires an vitro amino-terminal site, which conserved armadillo. mutants lacking this site more active inducing ectopic Xenopus embryos stable than wild-type...
Inherited and somatic mutations in the adenomatous polyposis coli occur most colon cancers, leading to activation of β-catenin-responsive genes. To identify small molecule antagonists this pathway, we challenged transformed colorectal cells with a secondary structure-templated chemical library, looking for compounds that inhibit reporter. We identified ICG-001, down-regulates β-catenin/T cell factor signaling by specifically binding cyclic AMP response element-binding protein. ICG-001...
In Drosophila, planar cell polarity (PCP) signaling is mediated by the receptor Frizzled (Fz) and transduced Dishevelled (Dsh). Wingless (Wg) also requires Dsh may utilize DFz2 as a receptor. Using heterologous system, we show that recruited selectively to membrane Fz but not DFz2, this recruitment depends on DEP domain PDZ in Dsh. A mutation impairs both localization function of PCP signaling, indicating translocation important for function. Further genetic molecular analyses suggest...
Understanding pathways controlling cardiac development may offer insights that are useful for stem cell-based repair. Developmental studies indicate the Wnt/β-catenin pathway negatively regulates differentiation, whereas with pluripotent embryonal carcinoma cells suggest this promotes cardiogenesis. This apparent contradiction led us to hypothesize signaling acts biphasically, either promoting or inhibiting cardiogenesis depending on timing. We used inducible promoters activate repress in...
Wnt signaling controls a variety of developmental processes. The canonical Wnt/beta-catenin pathway functions to stabilize beta-catenin, and the noncanonical Wnt/Ca(2+) activates Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). In addition, activated by Wnt-5a antagonizes via an unknown mechanism. mitogen-activated (MAPK) composed TAK1 MAPK NLK also negatively regulates pathway. Here we show that activation CaMKII induces stimulation TAK1-NLK Overexpression in HEK293 cells through...
The Wnt pathway regulates the early dorsal–ventral axis in Xenopus through a complex of β-catenin and HMG box transcription factors Lef/Tcf family. We show that promoter dorsalizing homeo gene siamois is direct target for β-catenin/XTcf-3 complex, establishing link between activation genes involved specifying dorsal axis. By injecting reporter constructs into animal pole embryos, we 0.8-kb fragment strongly activated by β-catenin. proximal 0.5 kb, which also β-catenin, contains three...
In contrast to mammals, lower vertebrates have a remarkable capacity regenerate complex structures damaged by injury or disease. This process, termed epimorphic regeneration, involves progenitor cells created through the reprogramming of differentiated activation resident stem cells. Wnt/beta-catenin signaling regulates cell fate and proliferation during embryonic development function in adults, but its functional involvement regeneration has not been addressed. Using transgenic fish lines,...