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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 PhD. 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 VCAPP as an Assistant
Professor in August 2007.
Selected Publications
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.
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