College of Veterinary Medicine

Research in IPN

Gary Wayman, Ph.D.


  

Assistant Professor
E-Mail: waymang@vetmed.wsu.edu
Office: VBR 335
Lab: (509) 335-6851
Phone: (509) 335-8211

Wayman Lab Website

 

Research

Normal cognitive processing, i.e. learning and memory consolidation, requires physical remodeling of synaptic connections. This remodeling commonly manifests as changes in dendritic arborization and alterations in the size, shape and density of dendritic spines. Since spines represent the site for excitatory synaptic inputs, modification of spine properties translates into changes in the efficacy of synaptic communication.  Not surprisingly, abnormalities in dendritic arborization and spinogenesis, which diminish neuronal connectivity, are a common feature of the cognitively compromised aging brain as well as numerous forms of mental retardation including Fragile X, Fetal alcohol, Downs and Rett syndromes.

It is clear that changes in synaptic activity and neurotrophic factors (e.g., BDNF) are effective initiators of the remodeling process and result in long-term alterations in dendrite and spine structure. What is not known are the molecular mechanisms that underlie how they stimulate dendritic spine formation.
 
The primary focus of my labs research is to determine the molecular and cellular mechanism by which synaptic activity and neurotrophic factors influence neuronal development. Our lab and others have demonstrate that synaptic activity and BDNF increase both intracellular calcium and the transcription of a subset of CREB-dependent genes, both of which are required to promote rearrangement of the cytoskeleton and formation of dendritic spines. We use a multidisciplinary approach combining disruption of key signaling cascades using dominant negative and constitutively active mutants, genetic manipulations and pharmacology with live imaging and confocal microscopy as well as both molecular and biochemical techniques to evaluate the roles of different CREB regulated gene products in regulating neuronal structural plasticity. As an outcome of our research we hope to determine the key CREB controlled genes activated by synaptic activity and BDNF, which regulate of neuronal morphogenesis, and to determine how they shape the development and modification of dendritic spines. In understanding the molecular players involved in these processes, one may in the future be able to develop therapies to treat neuronal developmental and/or psychiatric disorders. Thus our studies have strong implications for underlying causes of mental diseases.

Biographical Information

 

Gary A. Wayman received his B.S. in Biochemistry from Washington State University in 1988 and earned a Ph.D. in Pharmacology from the University of Washington in 1995. He then went on to postdoctoral training at the Vollum Institute, Oregon Health and Sciences University (OHSU) from 1995-2001. In 2001 he was promoted to Research Assistant Professor (Vollum Institute) and Assistant Professor (Department of Cell and Developmental Biology) at OHSU. Dr. Wayman joined the Department of IPN as an Assistant Professor in August 2007.

Selected Publications

Davare MA,  Fortin DA,  Saneyoshi T, Nygaard S, Kaech S, Banker G, Soderling TR, and Wayman GA. TRPC5 channels activate CaM-kinase Iγ to promote axon formation in hippocampal neurons.  In press J. Neuroscience.

Kim WY, Gonsiorek EA, Barnhart C, Davare MA, Engebose AJ, Lauridsen H, Brunn D, Lesiak A, Wayman G, Bucelli R, Higgins D, Lein PJ. Statins decrease dendritic arborization in rat sympathetic neurons by blocking RhoA activation. J. Neurochem, 2009, 108(4): 1057-71.

Yang D, Kim KH, Phimister A, Bachstetter AD, Ward TR, Stackman RW, Mervis RF, Wisniewski AB, Klein SL, Kodavanti PR, Anderson KA, Wayman G, Pessah IN, Lein PJ. Developmental exposure to polychlorinated biphenyls interferes with experience-dependent dendritic plasticity and ryanodine receptor expression in weanling rats. Environ Health Perspect. 2009 Mar;117(3):426-35. Epub 2008 Sep 12.

Luikart BW, Zhang W, Wayman GA, Kwon CH, Westbrook GL, Parada LF. Neurotropin-dependent dendritic filopodial motility: a convergence on PI3K signaling. J Neurosci. 2008 28(27): 7006-12.

Wayman, GA, Davare M, Ando H, Fortin D, Varlamova O, Cheng HY, Marks D, Obrietan K, Soderling TR, Goodman RH, Impey S.  An activity-regulated microRNA controls dendritic plasticity by down-regulating p250GAP.  Proc Natl Acad Sci U S A. 2008 Jul 1;105(26):9093-8. Epub 2008 Jun 24.

Wayman GA, Lee YS, Tokumitsu H, Silva A, Soderling TR. Calmodulin-kinases: modulators of neuronal development and plasticity.  Neuron 2008 59(6): 914-31. Review.

Saneyoshi T, Wayman G, Fortin D, Davare M, Hoshi N, Nozaki N, Natsume T, Soderling TR. Activity-Dependent Synaptogenesis: Regulation by a CaM-kinase kinase/CaM-kinase I/betaPIX signaling complex. Neuron. 2008 Jan 10;57(1):94-107.

Wayman GA, Impey S, Marks D, Saneyoshi T, Grant WF, Derkach V, Soderling TR. Activity-dependent dendritic arborization mediated by CaM-kinase I activation and enhanced CREB-dependent transcription of Wnt-2. Neuron. 2006 Jun 15;50(6):897-909.

Schmitt JM, Wayman GA, Nozaki N, Soderling TR. Calcium activation of ERK mediated by calmodulin kinase I. J Biol Chem. 2004 Jun 4;279(23):24064-72. Epub 2004 Mar 29.

Wayman GA*, Kaech S*, Grant WF, Davare M, Impey S, Tokumitsu H, Nozaki N, Banker G, Soderling TR. Regulation of axonal extension and growth cone motility by calmodulin-dependent protein kinase I. J Neurosci. 2004 Apr 14;24(15):3786-94. (*contributed equally to this work).

Soderling SH, Binns KL, Wayman GA, Davee SM, Ong SH, Pawson T, Scott JD. The WRP component of the WAVE-1 complex attenuates Rac-mediated signalling. Nat Cell Biol. 2002 Dec;4(12):970-5.

Impey S, Fong AL, Wang Y, Cardinaux JR, Fass DM, Obrietan K, Wayman GA, Storm DR, Soderling TR, Goodman RH. Phosphorylation of CBP mediates transcriptional activation by neural activity and CaM kinase IV. Neuron. 2002 Apr 11;34(2):235-44.

Walters MJ*, Wayman GA,* Notis JC, Goodman RH, Soderling TR, Christian JL. Calmodulin-dependent protein kinase IV mediated antagonism of BMP signaling regulates lineage and survival of hematopoietic progenitors. Development. 2002 Mar;129(6):1455-66. (*contributed equally to this work.)

Walters MJ, Wayman GA, Christian JL. Bone morphogenetic protein function is required for terminal differentiation of the heart but not for early expression of cardiac marker genes. Mech Dev. 2001 Feb;100(2):263-73.

Wayman GA, Walters MJ, Kolibaba K, Soderling TR, Christian JL. CaM kinase IV regulates lineage commitment and survival of erythroid progenitors in a non-cell-autonomous manner. J Cell Biol. 2000 Nov 13;151(4):811-24.

Impey S, Obrietan K, Wong ST, Poser S, Yano S, Wayman G, Deloulme JC, Chan G, Storm DR. Cross talk between ERK and PKA is required for Ca2+ stimulation of CREB-dependent transcription and ERK nuclear translocation. Neuron. 1998 Oct;21(4):869-83. PMID: 9808472 [PubMed - indexed for MEDLINE]

Xia XM, Fakler B, Rivard A, Wayman G, Johnson-Pais T, Keen JE, Ishii T, Hirschberg B, Bond CT, Lutsenko S, Maylie J, Adelman JP. Mechanism of calcium gating in small-conductance calcium-activated potassium channels. Nature. 1998 Oct 1;395(6701):503-7.

Wayman GA, Tokumitsu H, Soderling TR. Inhibitory cross-talk by cAMP kinase on the calmodulin-dependent protein kinase cascade. J Biol Chem. 1997 Jun 27;272(26):16073-6.

PubMed Publications (Note: This Publication Search may produce additional "Wayman" authors.)
Last Edited: Apr 09, 2013 10:28 AM   

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