Christopher Phiel photo
Ph.D. • Associate Professor
Department of Integrative Biology

Mailing Address:
Department of Integrative Biology
Campus Box 171
P.O. Box 173364
Denver, CO 80217-3364

Physical Location:
1151 Arapahoe
SI 4111
Denver, CO 80204

Office Hours:
BY APPOINTMENT ONLY

Expertise Areas:
The main interests in our lab revolve around understanding the functions of the enzyme glycogen synthase kinase-3 (Gsk-3) isoforms. We are utilizing a systems biology approach to understanding Gsk-3 function in maintaining pluripotency of embryonic stem cells. We have recently identified a role for Gsk-3 in regulating the methylation of mRNA. This modification, referred to as m6A, affects many aspects of RNA biology, including regulating the stability of mRNA and the translational efficiency. We are currently investigating the mechanisms underlying these effects, and their implications on the biology of stem cells.

1998 Ph.D. Developmental Biology Thomas Jefferson University, Philadelphia, PA
1992 B.S. Biology Ursinus College, Collegeville, PA

The main interests in our lab revolve around understanding the functions of the enzyme glycogen synthase kinase-3 (Gsk-3) isoforms. We are utilizing a systems biology approach to understanding Gsk-3 function in maintaining pluripotency of embryonic stem cells.

We have recently identified a role for Gsk-3 in regulating the methylation of mRNA. This modification, referred to as m6A, affects many aspects of RNA biology, including regulating the stability of mRNA and the translational efficiency. We are currently investigating the mechanisms underlying these effects, and their implications on the biology of stem cells.

Faulds, K.J., Egelston, J.N., Sedivy, L.J., Mitchell, M.K., Garimella, S., Kozlowski, H., D’Alessandro, A., Hansen, K.C., Balsbaugh, J.L., and Phiel, C.J. (2018) Glycogen synthase kinase-3 (Gsk-3) activity regulates mRNA methylation in mouse embryonic stem cells, Journal of Biological Chemistry, 293:10731-10743, doi:10.1074/jbc.RA117.001298, PMID: 29777057.

Tatavosian, R., Huynh, T.N., Duc, H.N., Fang, D., Schmitt, B., Grimm, J.B., Phiel, C.J., Lavis, L.D., Yao, T., Zhang, Z., Wang, H., and Ren, X. (2018) Live-Cell Single-Molecule Dynamics of PcG Proteins Imposed by the DIPG H3.3K27M Mutation, Nature Communications, 9:2080, DOI:10.1038/s41467-018-04455-7, PMID: 29802243.

Gonzalez Malagon, S.G., Lopez Munoz, A.M., Doro, D., Bolger, T.G., Poon, E., Tucker, E.R., Al-Lami, H.A., Krause, M., Phiel, C.J., Chesler, L., and Liu, K.J. (2018) Glycogen Synthase Kinase-3 Controls Migration of the Cranial Neural Crest Lineage in Mouse and Xenopus, Nature Communications, 9:1126, DOI:10.1038/s41467-018-03512-5, PMID: 29555900.

Bhattacharjee, R. Goswami, S., Dey, S., Gangoda, M., Brothag, C., Eisa, A., Woodgett, J., Phiel, C.J., Kline, D., and Vijayaraghavan, S. (2018) Isoform-Specific Requirement for GSK-3α in Sperm for Male Fertility, Accepted, Biology of Reproduction, DOI:10.1093/biolre/ioy020, PMID: 29385396.

Fowler, J.J., Braley, K.L., Farero, R.D., Russell, E., Phiel, C.J., Kisley, M.A., and Albeck, D.S. (2018) The late positive potential and subjective arousal ratings evoked by negative images vary as a function of oxytocin receptor genotype SNP rs53576, NeuroReport, DOI: 10.1097/WNR.0000000000001085, PMID: 29958244.

Nakamura, M., Liu, T., Husain, S., Zhai, P., Warren, J.S., Hsu, C.-P., Matsuda, T., Phiel, C.J., Cox, J., Tian, B., Klein, P.S., Li, H., Sadoshima, J. (2018) Glycogen Synthase Kinase-3α Promotes Fatty Acid Anabolism and Lipotoxic Cardiomyopathy, Submitted.

Meredith G, D'Ippolito A, Zeidner LC, Hostetter L, Popkie AP, Doble BW, Marnellos G, Adams C, Wang Y, and Phiel CJ (2015) Glycogen Synthase Kinase-3 (Gsk-3) Plays a Fundamental Role In Maintaining DNA Methylation At Imprinted Loci In Mouse Embryonic Stem Cells, Molecular Biology of the Cell, 26: 2139-2150, PMID: 25833708.

Battacherjee R, Dudki T, Goswami S, Popkie A, Phiel CJ, Kline D, and Vijayaraghavan S (2015) Targeted disruption of GSK-3α affects sperm motility resulting in male infertility, Biology of Reproduction, 92: 1-12, PMID: 25568307.

Bartman CM, Egelston J, Ren X, Das R, and Phiel CJ (2015) A Simple and Efficient Method for Transfecting Mouse Embryonic Stem Cells Using Polyethylenimine, Experimental Cell Research 330: 178-185, PMID: 25102378.

Zhen CY, Duc, HN, Kokotovic M, Phiel CJ, and Ren X (2014) Immobilization of PRC1 Complex at Mitotic Chromosomes by Cbx2 in a PRC2-Independent Mechanism, Molecular Biology of the Cell 25(23):3726-3739, PMID: 25232004.

Bartman CM, Egelston J, Zeidner LC, D'Ippolito, A, Kattula S, Doble BW, and Phiel CJ (2014) Gene expression profiling in mouse embryonic stem cells reveals glycogen synthase kinase-3-dependent targets of phosphatidylinositol 3-kinase and Wnt/β-catenin signaling pathways, Frontiers in Endocrinology 5:133, PMID: 25165462.

Phiel CJ, Wilson CA, Lee VM-Y and Klein PS (2011) Reply to GSK-3α/β kinases and amyloid production in vivo, Nature 480:E6, PMID: 22158251.

Zeidner LC, Buescher JL, and Phiel CJ (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 JL, Phiel CJ, and Toland AE (2011) The Role for Oxidative Stress in Aberrant DNA Methylation in Alzheimer's Disease, Current Alzheimer Research 9(9):1077-1096, PMID: 21605062.

Popkie AP, Zeidner LC, Albrecht AM, D'Ippolito A, Eckardt S, Newsom DE, Groden J, Doble BW, Aronow B, McLaughlin KJ, White P, Phiel CJ (2010) Phosphatidylinositol 3-Kinase (PI3K) Signaling via Glycogen Synthase Kinase-3 (Gsk-3) Regulates DNA Methylation of Imprinted Loci., Journal of Biological Chemistry 285(53):41337-47, PMID: 21047779.

He F, Popkie AP, Xiong W, Li L, Wang Y, Phiel CJ, Chen Y. (2010) Gsk3β is required in the epithelium for palatal elevation in mice., Developmental Dynamics 239(12):3235-46, PMID: 20981831.

Yang J, Phiel CJ. (2010) Functions of B56-containing PP2As in major developmental and cancer signaling pathways., Life Sciences 87(23-26):659-66. Review, PMID: 20934435.

Buescher JL and Phiel CJ (2010) A non-catalytic domain of glycogen synthase kinase-3 (GSK-3) is essential for activity,Journal of Biological Chemistry 285:7957-7963, PMID: 20080974.

Rorick AM, Mei W, Liette NL, Phiel C, El-Hodiri HM, Yang J. (2007) PP2A:B56epsilon is required for eye induction and eye field separation., Developmental Biology 302(2):477-93, PMID: 17074314.

Checler F, Alves da Costa C, Ayral E, Andrau D, Dumanchin C, Farzan M, Hernandez JF, Martinez J, Lefranc-Jullien S, Marambaud P, Pasini A, Petit A, Phiel CJ, 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 CJ, Wilson CA, Lee VM-Y and Klein PS (2003) GSK-3α Regulates Production of Alzheimer's Disease Amyloid-β Peptides, Nature 423:435-439, PMID: 12761548.

Zhang F, Phiel CJ, Spece L, Gurvich N and Klein PS (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 JF, Dumanchin-Njock C, Phiel CJ, 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 WT, Phiel CJ and McHugh KM (2003) Vesicle-Associated Protein-A is Differentially Expressed During Intestinal Smooth Muscle Cell Differentiation, Developmental Dynamics 228:11-20, PMID: 12950075.

Phiel CJ, Zhang F, Huang EY, Guenther MG, Lazar MA and Klein PS (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 CJ and Klein PS (2001) Molecular Targets of Lithium Action, Annual Reviews in Pharmacology and Toxicology 41:789-813, PMID: 11264477.

Phiel CJ, Gabbeta V, Parsons LM, Rothblat D, Harvey RP and McHugh KM (2001) Differential binding of an SRF/NK-2 transcription factor complex in normal versus neoplatic smooth muscle tissues, Journal of Biological Chemistry 276:34637-34650, PMID: 11457859.

Brittingham JW*, Phiel CJ*, Trzyna WT*, Gabbeta V, and McHugh KM (1998) Identification of Distinct Molecular Phenotypes in Cultured Gastrointestinal Smooth Muscle Cells, Gastroenterology 115:605-617, PMID: 9721158 (*Authors contributed equally).

Kelsie J. Faulds‡1, Jennifer N. Egelston‡1, Laura J. Sedivy‡1, Matthew K. Mitchell‡, Sanjana Garimella‡,Hanna Kozlowski‡, Angelo D’Alessandro52, Kirk C. Hansen§, X Jeremy L. Balsbaugh¶3, and  Christopher J. Phiel‡4 From the ‡Department of Integrative Biology, University of Colorado Denver, Denver, Colorado 80204, the §Department of Biochemistry and Molecular Genetics, University of Colorado Denver, Aurora, Colorado 80045, and the ¶Mass Spectrometry Core Facility, Department of Chemistry and Biochemistry, University of Colorado Boulder, Boulder, Colorado 80309 Edited by Eric R. Fearon
Glycogen synthase kinase-3 (GSK-3) activity regulates mRNA methylation in mouse embryonic stem cells
Received for publication, December 20, 2017, and in revised form, May 9, 2018 Published, Papers in Press, May 18, 2018, DOI 10.1074/jbc.RA117.001298 http://www.jbc.org/

BIOL 3124 Introduction to Molecular Biology
BIOL4125/5125 Molecular Biology Lab
BIOL 4128/5128 Topics In Molecular Biology