Kenneth Cadigan

cadigan's picture
University: 
University of Michigan - Ann Arbor
Unit: 
LSA: Natural Sciences
Department: 
Molecular, Cellular, and Developmental Biology (MCDB)
Title: 
Professor of Molecular, Cellular and Developmental Biology
Phone: 
734-936-3246
Short bio: 

Born and raised in northeast New Jersey.  Graduated cum laude with a B.A. in zoology from Connecticut College in 1983.  Completed a PhD in Biochemistry from Dartmouth Medical School in 1989.  Post-doctoral training at the Biozentrum in Basel Switzerland and Stanford University.  Since 1998, has been on the faculty of the University of Michigan.

Research summary: 

My laboratory investigates the mechanisms by which the Wnt/beta-catenin signaling pathway regulates target gene expression.  I have a broad background in enzymology, cell culture and Drosophila developmental genetics that instructs our experimental approach.  As a graduate student at Dartmouth, I identified Chinese Hamster Ovary cells that were defective in acyl CoA cholesteryl acyl transferase (ACAT, also known as sterol O-acyltransferase) which I then complemented with human genomic DNA containing the human ACAT gene.  This work led to the initial cloning of the ACAT cDNA.  I also isolated mutants defective in transport of intracellular cholesterol which were subsequently shown to be mutant in the Niemann-Pick type C1 gene.  My post-doctoral training was first at the Biozentrum where I characterized the role of the Sloppy paired proteins in Drosophila segmentation.  I then trained at Stanford University, where I worked on the mechanisms of Wnt signal transduction in Drosophila, most notably contributing to the discovery that the Frizzled 2 protein is a physiologically important receptor for the fly Wnt ligand Wingless.  Since establishing my own research program at the University of Michigan, my group has increasingly focused on transcriptional regulation by the Wnt/beta-catenin pathway, identifying several key co-regulators that mediate transcriptional responses.  Some of these factors have been linked to chromatin modifications that occur at Wnt target loci in response to pathway activation.  Most of our current work in focuses on how TCF, the transcription factor that is regulated by Wnt signaling, locates targets in the nucleus to either activate or repress transcription.  This work is supported by grants from the NIH and NSF.  In addition, we are extending our research to other systems, such as C. elegansXenopus and mammals, where we are finding that gene regulation by Wnt signaling shares many similarities with Drosophila, but there are also important differences.  We believe this multi-organismal approach is required for a complete understanding of how Wnt/beta-catenin signaling influences the cell's transcriptome in normal development and disease.

Recent publications: 

Chang, J. L., Lin, H. V., Blauwkamp, T. A. and Cadigan, K. M. (2008) Spenito and Split ends act reduntantly to promote Wingless signaling.  Dev. Biol., 314: 100-111.

Parker, D. S., Ni, Y. Y., Chang, J. L., Li, J. and Cadigan, K. M. (2008) Wingless signaling induces widespread chromatin remodeling of target loci.  Mol. Cell. Biol., 28:1815-1828.

Cadigan, K. M. (2008) Wnt/b-catenin signaling: turning the switch.  Dev. Cell 14: 322-323.

Blauwkamp, T. A., Chang, M. V. and Cadigan, K. M. (2008) Novel TCF Binding Sites Specify Transcriptional Repression by Wnt Signaling.  EMBO J. 27:1436-1446. 

Chang, J. L., Chang, M. V., Barolo, S. and Cadigan, K. M. (2008) Regulation of the feedback antagonist naked cuticle by Wingless signaling.  Dev. Biol. 321: 446-454.

Liu, Y. I., Chang, M. V., Li, H. E., Barolo, S., Chang, J. L., Blauwkamp, T.  A. and Cadigan, K. M. (2008) The chromatin remodelers ISWI and ACF1 directly repress Wingless transcriptional targets.  Dev. Biol. 323: 41-52.

Kennell, J. Gerin, I., MacDougald, O. A. and Cadigan, K. M. (2008) The microRNA miR-8 is a conserved negative regulator of Wnt signaling.  Proc. Natl. Acad. Sci. USA 105: 15417-15422.

Cadigan, K. M. (2008) Wnt-beta-catenin signaling. Curr. Biol. 18: R943-947.

Grieder, N. C., Caussinus, E., Parker, D. S., Cadigan, K. M., Affolter, M. and S. Luschnig (2008) gammaCOP is required for apical protein secretion and epithelial morphogenesis in Drosophila melanogaster. PLoS ONE, 3: e3241.

Chang, M. V., Chang, J. L., Gangopadhyay, A., Shearer, A. and Cadigan, K. M. (2008) Activation of Wingless targets requires bipartite recognition of DNA by TCF. Curr. Biol. 18: 1877-1881.

Fang, M., Ren, H., Liu, J, Cadigan, K. M., Patel, S. R. and Dressler, G. R. (2009) Drosophila ptip is essential for anterior/posterior patterning in development and interacts with the PcG and trxG pathways. Development 136: 1929-1938. PMCID: PMC2680114

Kennell J. A. and Cadigan, K. M. (2009) APC and beta-catenin degradation.  Adv. Exp. Med. Biol. 656: 1-12.

Cadigan, K. M. and Peifer, M. (2009) Wnt signaling from development to disease: Insights from model systems.  Cold Spring Harbor Perspectives in Biology. 1: a002881.

Cadigan, K. M. (2010) Receptor endocytosis: Frizzled joins the ubiquitin club.  EMBO J. 29: 2099-2100.

Bhambhani, C., Chang, J. L., Akey, D. L. and Cadigan, K. M. (2011) The oligomeric state of CtBP determines its role as a transcriptional co-activator and co-repressor of Wingless targets. EMBO J. 30: 2031-2043.

Archbold, H. A., Yang, Y. X. Chen, L. and Cadigan, K. M. (2012) How can they do Wnt they do: regulation of transcription by Wnt/b-catenin signaling.  Acta Physiologica, 204: 74-109.

Kennell, J. A., Cadigan, K. M., Shakhmanstir, I. and Waldron E. J. (2012) The microRNA miR-8 is a positive regulator of pigmentation and eclosion in Drosophila.  Dev. Dyn. 241: 161-168.

Cadigan, K. M. (2012) TCFs and Wnt/beta-catenin Signaling: More than one way to throw the Switch. Curr. Topics in Dev. Biology, 98: 1-34.

Keywords: 
Wnt; beta-catenin; TCF; gene regulation