Directory | Contact | Careers | Intranet | Home

Research Focus

Molecular mechanisms of functional and structural plasticity of glutamatergic synapses

The overall goal of our group is to define molecular mechanisms involved in the production of synaptic plasticity. Current work in our laboratory is focused on defining interrelationships between dendritic protein synthesis and the structure and function of glutamatergic connections. Enduring forms of synaptic plasticity, such as long-term potentiation (LTP), require translation of dendritically localized mRNAs for their persistence and are correlated with changes in the morphology of dendritic spines. We have developed reagents based on fluorescent fusion protein constructs that report in situ the activation of enzymes required for LTP. In collaboration with others in the department, we have also generated constructs that report the translation of dendritically localized mRNAs. Using these tools and biochemical approaches we are testing the hypothesis that dendritic protein synthesis contributes to structural modifications of synapses and, reciprocally, that the structure of a synapse has a regulatory influence on local translation.

Education

Ph.D., Neurobiology, University of California, Irvine, 1997

Awards & Professional Activities

2009-2013: NIH/NINDS, Research Project Grant (R01)
2008-2010: The Del E. Webb Foundation Grant
2004-2008: FRAXA Research Foundation Grant
2001-2004: NIH/NIMH, Mentored Research Scientist Development Award (K01)

Selected References

Henderson C, Wijetunge L, Kinoshita MN, Shumway M, Hammond RS, Postma FR, Brynczka C, Rush R, Thomas A, Paylor R, Warren ST, Vanderklish PW, Kind PC, Carpenter RL, Bear MF, Healy AM. Reversal of disease-related pathologies in the fragile X mouse model by selective activation of GABA(B) receptors with arbaclofen.  Sci Transl Med. 2012 Sep 19;4(152):152ra128.

Liao L, Sando RC, Farnum JB, Vanderklish PW, Maximov A, Yates JR.  15N-labeled brain enables quantification of proteome and phosphoproteome in cultured primary neurons. J Proteome Res. 2012 Feb 3;11(2):1341-53.

Pilotte J, Dupont-Versteegden EE, Vanderklish PW. Widespread regulation of miRNA biogenesis at the Dicer step by the cold-inducible RNA-binding protein, RBM3.  PLoS One. 2011;6(12):e28446.

Ferry AL, Vanderklish PW, Dupont-Versteegden EE.  Enhanced survival of skeletal muscle myoblasts in response to overexpression of cold shock protein RBM3.  Am J Physiol Cell Physiol. 2011 Aug;301(2):C392-402.

Pilotte J, Cunningham BA, Edelman GM, Vanderklish PW. Developmentally regulated expression of the cold-inducible RNA-binding motif protein 3 in euthermic rat brain. Brain Res. 2009 Mar 3;1258:12-24. 

Liao L, Park SK, Xu T, Vanderklish P, Yates JR 3rd. Quantitative proteomic analysis of primary neurons reveals diverse changes in synaptic protein content in fmr1 knockout mice. Proc Natl Acad Sci U S A. 2008 Oct 7;105(40):15281-6