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Neuroscience Graduate Program at UCSF
Signaling and the Cytoskeleton during Embryonic Development and in Brain Cells
We are investigating intracellular proteins that regulate signaling pathways and cytoskeletal dynamics in neurons. We seek to understand how these proteins operate both in the developing embryo and in the brain. Our embryonic studies are particularly relevant to birth defects, whereas our brain studies are relevant to the biology of mental illnesses such as autism, schizophrenia, and bipolar disorder. We have found that these approaches are highly complementary: our discoveries in the embryo inform our investigations in the brain and vice-versa. For example, our recent work has uncovered critical dual roles for one protein during gastrulation (embryonic tissue morphogenesis) at the primitive streak, as well as later in the formation and maintenance of dendrites and synapses. The experimental tools we primarily use are recombinant DNA technology, mammalian tissue culture, and gene-targeted and transgenic strains of laboratory mice.
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
Ben Cheyette
PI
bc@lppi.ucsf.edu
Saul Kivimae
Post-doctoral fellow
skivimae@lppi.ucsf.edu
XiaoYong Yang
Post-doctoral fellow
xiao.yang@ucsf.edu
Pierre-Marie Martin
Post-doctoral fellow
pierre.martin@ucsf.edu
Nathan Okerlund
Graduate Student
Neuroscience Program
nathan.okerlund@ucsf.edu
Annie Arguello
Graduate Student
BMS Program
annie.arguello@ucsf.edu
Okerlund ND, Kivimäe S, Peng I-f, Ullian EM, Cheyette BNR. Mammalian hippocampal neurons require Dact1 for dendrite, spine, and excitatory synapse development. under review
Suriben R, Kivimäe S, Fisher DA, Moon RT, Cheyette, BNR. Posterior Malformations in Dact1 mutant mice arise through misregulated Vangl2 at the Primitive Streak. Nat Genet, http://dx.doi.org/10.1038/ng.435
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.
Benjamin Cheyette, MD/Ph.D.
Phone
415-476-7826
Physical Address
Rock Hall
1550 4th Street
RH-284D
Mailing Address
Cheyette Lab
UCSF MC 2611
Rock Hall Room 284D
1550 4th St
San Francisco, CA 94158-2324
For Internal Campus Mail
Box 2611
Other Websites
Biomedical Sciences Graduate Program
Pharmaceutical Sciences & Pharmacogenomics