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Neuroscience Graduate Program at UCSF

Faculty - Benjamin Cheyette, MD/Ph.D.

Signaling Scaffold Proteins in Development and Major Psychiatric Disorders


Research Description

The major direction of research in my laboratory is to use transgenic mouse models, primary neural cell culture, and other molecular tools to investigate neurodevelopmental and behavioral functions of genes/proteins implicated in psychiatric disease through contemporary large-scale human genetic studies.  There is broad consensus that major psychiatric disorders have a substantial developmental component and can result from defects in the organization of neurons as they are born, mature, and grow.  The molecules that are a focus of research in my laboratory are involved in intercellular signaling pathways that contribute to these biological processes: in particular we specialize in the Wnt signaling pathway based on several lines of evidence that disruption of this pathway can contribute to major mental disorders and is a target of psychiatric pharmacology.  Our studies have honed in on the role of this pathway in the development of synapses and of neuronal architecture in the forebrain, especially the prefrontal cortex. 

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Current Projects

1. Characterization of neuron and brain phenotypes resulting from novel targeted mutations in mice

2.  Identification of mental-illness-associated gene variants in human populations and their effects on neuron morphology, function, and on behavior in mouse models

3. Elucidation of novel biochemical pathways operating in neurons involving the genes/proteins in #1 and #2

4. Mechanistic investigations of embryological phenotypes resulting from the same novel targeted mutations in mice, when operating earlier and elsewhere in development

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Lab Members

Pierre-Marie Martin, Postdoctoral Fellow
Petros Minasi, Lab Manager
Robert Stanley, Graduate Student
Andiara Espindola de Freita, Postdoctoral Fellow
Adam Ross, Postdoctoral Fellow
Susan Yu, Administrative Assistant

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Selected Publications

Martin, P-M, Yang, XY, Robin, N, Lam, E, Rabinowitz, JS, Erdman, CA, Quinn, J, Weiss, LA, Hamilton, SP, Kwok, P-Y, Moon, RT, Cheyette, BNR  A rare WNT1 missense variant over-represented in ASD leads to increased Wnt signal pathway activation.  Translational Psychiatry, 2013 Sep 3:3:e301.

Arguello, A, Yang XY, Vogt D, Stanco, A, Rubenstein, JLR, Cheyette BNR  Dapper Antagonist of Catenin-1 cooperates with Dishevelled-1 during postsynaptic development in mouse forebrain GABAergic interneurons.  PLoS ONE, 8: e67679, 2013.

Yang, XY and Cheyette BNR The SEC14 and spectrin domains 1 (Sestd1) and Dapper antagonist of catenin 1 (Dact1) scaffold proteins cooperatively regulate the Van Gogh-like 2 (Vangl2) 4-pass transmembrane protein and planar cell polarity (PCP) pathway during embryonic development in mice.  J Biol Chem (Cover article & Paper of the Week), 288: 20111-20, 2013

Mulligan, K, Cheyette BNR (2012)  Wnt Signaling in Neural Development and Function.  Journal of NeuroImmune Pharmacolog, 7: 774-87, 2012

Kivimäe S, Yang, XY, Cheyette BNR. Dimerization and conserved complex formation with Vangl, Dvl and Ck1d/e proteins. BMC Biochemistry (Highly accessed), 12: 33, 2011

Kivimäe S, Martin P-M, Kapfhamer D, Ruan Y, Heberlein U, Rubenstein JLR, Cheyette BNR.  Abnormal behavior in mice mutant for the Disc1 binding partner, Dixdc1. Translational Psychiatry, 1, e43, 2011.

Okerlund ND, Cheyette BNR.  Synaptic Wnt Signaling – A Contributor to Major Psychiatric Disorders? J. Neurodev Di, 3: 162-742010

Okerlund ND, Kivimäe S, Peng I-f, Ullian EM, Cheyette BNR.  Mammalian hippocampal neurons require Dact1 for dendrite, spine, and excitatory synapse development.  J Neurosci, 30: 4362-8, 2010

Suriben R, Kivimäe S, Fisher DA, Moon RT, Cheyette, BNR.  Posterior Malformations in Dact1 mutant mice arise through misregulated Vangl2 at the Primitive Streak. Nature Genetics 41, 977 - 985 (2009)

Louie S, Yang XY, Conrad WH, Muster J, Angers S, Moon RT, Cheyette BNR. Modulation of the ß-catenin Signaling Pathway by the Dishevelled-associated Protein Hipk1.  PLoS ONE, 4: e4310, 2009.

Cheyette, BNR, Cheyette, SNR, Cusmano-Ozog, K, Enns, GM. Dopa-responsive dystonia presenting as delayed and awkward gait. Pediatric Neurology, 38: 273-275, 2008.

Jiang, T, Tan, J, Li, J, Kivimäe, S, Zhuang, L, Lee, PY, Chan, MTW, Liu, ET, Cheyette, BNR, Yu, Q.  DACT3 is a Key Epigenetic Regulator of Wnt/ß-catenin Signaling in Colorectal Cancer and is a Therapeutic Target of Histone Modifications. Cancer Cell, 13: 529-541, 2008.

Suriben, R., Fisher, DA, Cheyette, BNR. Dact1 Presomitic Mesoderm Expression Oscillates in phase with Axin2 in the Somitogenesis Clock of Mice. Dev Dyn, 235: 3177-3183, 2006.

Fisher, DA, Kivimäe, S, Hoshino, J, Suriben, R, Martin, P-M, Baxter, N, Cheyette, BNR. Three Dact Gene Family Members are Expressed During Embryonic Development and in the Adult Brains of Mice. Dev Dyn Mouse Development Special Issue, 235: 2620-2630, 2006.

Kovoor, A, Seyffarth, P, Ebert, J, Barghshoon, S, Ching-Kang, C, Schwarz, S, Axelrod, JD, Cheyette, BNR, Simon, MI, Lester, HA, and Schwarz, J.  D2-dopamine Receptors Colocalize RGS9-2 via the RGS9 DEP domain and RGS9 knockout mice develop dyskinesias associated with dopamine pathways. J Neurosci, 25: 2157-65, 2005.

Cheyette, BNR, Waxman, JS, Miller, JR, Takemaru, KI, Sheldahl, LC, Khlebtsova, N, Fox, EP, Earnest, T, and Moon, RT.  Dapper, a Dishevelled-Associated Antagonist of ß-catenin and JNK Signaling, is required for Notochord Formation, Developmental Cell, 2: 449-461, 2002.

Cheyette, BNR, Green, PJ, Martin, K, Garren, H, Hartenstein, V, and Zipursky, SL. (1994) The Drosophila sine oculis locus encodes a homeodomain-containing protein required for the development of the entire visual system. Neuron, 12: 977-996, 1994.

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Benjamin Cheyette, MD/Ph.D.



Email

bc@ucsf.edu

Phone

415-476-7826

Office Address

UCSF MC 2611
1550 4th Street, RH-284D
San Francisco, CA 94158

Other Websites

Biomedical Sciences Graduate Program

Developmental & Stem Cell Biology Graduate Program

Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research

Lab Website

PIBS Website

Pharmaceutical Sciences & Pharmacogenomics

Psychiatry