University of Colorado Denver College of Liberal Arts and Sciences

There are two main interests in our lab. First, we are interested in understanding the various biological functions regulated by glycogen synthase kinase-3 (Gsk-3) isoforms. We are utilizing a systems biology approach to understanding Gsk-3 function in embryonic stem cells, neuronal cells, mice, and humans. These studies have shown that Gsk-3 activity is important for regulating DNA methylation, and we are very interested in learning more about how signal transduction affects epigenetics.

Second, we are interested in understanding the mechanism of the ketogenic diet, which is used to treat epilepsy in children whose seizures are not controlled by drugs. Through an active collaboration with the Child Neurology Clinic here at Children's Hospital Colorado, we are making inroads into how this diet works. A fundamental understanding of the ketogenic diet could lead to better predictions of who will benefit most from the diet, and may eventually result in the development of better treatments.​

Publications

Phiel, C.J., Wilson, C.A., Lee, V.M.-Y., and Klein, P.S. (2011) Reply to GSK-3α/β

kinases and amyloid production in vivo, Nature, 480:E6. PMID: 22158251.

 

Zeidner, L.C., Buescher, J.L., and Phiel, C.J. (2011) A Novel Interaction Between

Glycogen Synthase Kinase-3α (GSK-3α) and the Scaffold Protein Receptor for Activated

C-Kinase 1 (RACK1) Regulates the Circadian Clock, International Journal of

Biochemistry and Molecular Biology, 2(4):318-327. PMID: 22187666.

 

Fleming, J.L., Phiel, C.J., and Toland, A.E. (2011) The Role for Oxidative Stress in

Aberrant DNA Methylation in Alzheimer’s Disease, Current Alzheimer Research, In

Press. PMID: 21605062.

 

Popkie, A.P., Zeidner, L.C., Albrecht, A.M., D’Ippolito, A., Eckardt, S., Newsom, D.E.,

Groden, J., Doble, B.W., Aronow, B., McLaughlin, K.J., White, P., and Phiel, C.J. (2010)

Phosphatidylinositol 3-Kinase (PI3K) Signaling via Glycogen Synthase Kinase-3 (Gsk-3)

Regulates DNA Methylation of Imprinted Loci, Journal of Biological Chemistry, 285:

41337-41347. PMID: 21047779.

 

Buescher, J.L. and Phiel, C.J. (2010) A Noncatalytic Domain of GSK-3 Is Essential for

Activity, Journal of Biological Chemistry, 285:7957-7963. PMID: 20080974.

 

He, F., Popkie, A.P., Xiong, W., Li, L., Phiel, C.J.*, and Chen, Y. (2010) Gsk-3β is

Required in the Epithelium for Palatal Elevation in Mice, Developmental Dynamics,

239:3235-3246. PMID: 20981831 (*Co-corresponding author).

 

Yang, J. and Phiel, C.J. (2010) Functions of B56-Containing PP2As in Major

Developmental and Cancer Pathways, Life Sciences, 87:659-666. PMID:20934435.

 

Rorick, A.M., Mei, W., Liette, N.L., Phiel, C.J., El-Hodiri, H., and Yang, J. (2007)

PP2A:B56e is Required For Eye Induction and Eye Field Separation, Developmental

Biology, 302:477-493. PMID: 17074314.

 

Checler, F., Alves da Costa, C., Ayral, E., Andrau, D., Dumanchin, C., Farzan, M.,

Hernandez, J.F., Martinez, J., Lefranc-Jullien, S., Marambaud, P., Pasini, A., Petit, A.,

Phiel, C.J., Robert, P., St. George-Hyslop, P., and Wilk, S. (2005) JLK Inhibitors:

Isocoumarin Compounds as Putative Probes to Selectively Target the γ-Secretase

Pathway, Current Alzheimer Research, 2:327-334. PMID: 15974898.

 

Phiel, C.J., Wilson, C.A., Lee, V.M.-Y., and Klein, P.S. (2003) GSK-3α Regulates

Production of Alzheimer’s Disease Amyloid-β Peptides, Nature, 423:435-439. PMID:

12761548. 

 

Zhang, F., Phiel, C.J., Spece, L., Gurvich, N., and Klein, P.S. (2003) Inhibitory

Phosphorylation of Glycogen Synthase Kinase-3 (GSK-3) in Response to Lithium:

Evidence for Autoregulation of GSK-3, Journal of Biological Chemistry, 278:33067-

33077. PMID: 12796505.

 

Checler, F., Pasini, A., Alves da Costa, C., Ayral, E., Hernandez, J.F., Dumanchin-Njock,

Phiel, C.J., Marambaud, P., Wilk, S., Farzan, M., Boisbrun, M., Fulcrand, P., Martinez,

J., Andrau, D., and Petit, A. (2003) JLK isocoumarin inhibitors: Selective γ-Secretase

Inhibitors That Do Not Interfere With Notch Pathway In Vitro or In Vivo, Journal of

Neuroscience Research, 74:370-377. PMID: 14598313.

 

Gabetta, V., Trzyna, W.T., Phiel, C.J., and McHugh, K.M. (2003) Vesicle-Associated

Protein-A is Differentially Expressed During Intestinal Smooth Muscle Cell

Differentiation, Developmental Dynamics, 228:11-20. PMID: 12950075.

 

Phiel, C.J., Zhang, F., Huang, E.Y., Guenther, M.G., Lazar, M.A., and Klein, P.S. (2001)

Histone Deacetylase is a Direct Target of Valproic Acid, a Potent Anticonvulsant, Mood

Stabilizer, and Teratogen, Journal of Biological Chemistry, 276:36734-36741. PMID:

11473107.

 

Phiel, C.J. and Klein, P.S. (2001) Molecular Targets of Lithium Action, Annual Reviews

in Pharmacology and Toxicology, 41:789-813. PMID: 11264477.

 

Phiel, C.J., Gabbeta, V., Parsons, L.M., Rothblat, D., Harvey, R.P., and McHugh, K.M.

(2001) Differential Binding of an SRF/NK-2 Transcription Factor Complex in Normal

Versus Neoplastic Smooth Muscle Tissues, Journal of Biological Chemistry, 276:34637-

34650. PMID: 11457859.

 

Brittingham, J.W. *, Phiel, C.J. *, Trzyna, W.T. *, Gabbeta, V., and McHugh, K.M. (1998)

Identification of Distinct Molecular Phenotypes in Cultured Gastrointestinal Smooth

Muscle Cells. Gastroenterology 115:605-617. PMID: 9721158. (*Authors contributed

equally).

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​BIOL 4128/5128 Topics In Molecular Biology