Associate Professor, Director Undergraduate Neuroscience Program
Nervous system development; ubiquitin; protein degradation
My laboratory is interested in identifying genes essential for the development and function of the peripheral nervous system. Using spontaneously occurring neurological mouse mutations, we have identified several critical regulators of neuronal signaling during development. Our studies of these mouse mutants have demonstrated that ubiquitin signaling is required during multiple steps of nervous system development to control protein abundance as well as the activation of protein kinases.
Our current approaches utilize both in vivo and in vitro systems to explore the requirements of the ubiquitin-proteasome system in regulating neuronal function. These approaches include the development of conditional knockout mice to evaluate the requirement of different gene products in specific neural populations and the culturing of primary neural cells to identify the cellular pathways that are regulated by ubiquitin signaling.
Watson JA, Bhattacharyya BJ, Vaden JH, Wilson JA, Icyuz M, Howard AD, Phillips E, DeSilva TM, Siegal GP, Bean AJ, King GD, Phillips SE, Miller RJ, Wilson SM. 2015. Motor and Sensory Deficits in the teetering Mice Result from Mutation of the ESCRT Component HGS.PLoS Genet. 2015 Jun 26;11(6):e1005290.
Vaden JH, Watson JA, Howard AD, Chen PC, Wilson JA, Wilson SM. 2015. Distinct effects of ubiquitin overexpression on NMJ structure and motor performance in mice expressing catalytically inactive USP14. Front Mol Neurosci. 2015 Apr 23;8:11.
Vaden JH, Bhattacharyya BJ, Chen PC, Watson JA, Marshall AG, Phillips SE, Wilson JA, King GD, Miller RJ, Wilson SM. 2015. Ubiquitin-specific protease 14 regulates c-Jun N-terminal kinase signaling at the neuromuscular junction. Mol Neurodegeneration 10(1):3
Walters BJ, Hallengren JJ, Theile CS, Ploegh HL, Wilson SM*, Dobrunz LE*. 2014. A catalytic independent function of the deubiquitinating enzyme USP14 regulates hippocampal short-term synaptic plasticity and vesicle number. J Physiol. 2014 Feb 15;592(Pt 4):571-86
Jarome TJ, Kwapis JL, Hallengren JJ, Wilson SM, Helmstetter FJ. 2013. The ubiquitin-specific protease 14 (USP14) is a critical regulator of long-term memory formation. Learn Mem. 2013 Dec 16;21(1):748-52.
Marshall AG, Watson JA, Hallengren JJ, Walters BJ, Dobrunz LE, Francillon L, Wilson JA, Phillips SE, Wilson SM. 2013. Genetic background alters the severity and onset of neuromuscular disease caused by the loss of ubiquitin-specific protease 14 (usp14).PLoS One. 2013 Dec 16;8(12):e84042
Chen PC, Bhattacharyya BJ, Hanna J, Minkel H, Wilson JA, Finley D, Miller RJ, Wilson SM. 2011. Ubiquitin homeostasis is critical for synaptic development and function. J Neurosci.31(48):17505-13
Lee BH, Lee MJ, Park S, Oh DC, Elsasser S, Chen PC, Gartner C, Dimova N, Hanna J, Gygi SP, Wilson SM, King RW, Finley D. 2010. Enhancement of proteasome activity by a small-molecule inhibitor of USP14. Nature 467(7312):179-84.
Chen PC, Qin LN, Li XM, Walters BJ, Wilson JA, Mei L, Wilson SM. 2009. The proteasome-associated deubiquitinating enzyme Usp14 is essential for the maintenance of synaptic ubiquitin levels and the development of neuromuscular junctions. J Neurosci. 29(35):10909-19.
Cartier AE, Djakovic SN, Salehi A, Wilson SM, Masliah E, Patrick GN. 2009. Regulation of synaptic structure by ubiquitin C-terminal hydrolase L1.J Neurosci. 29(24):7857-68.
Ph.D., Genetics, University of Florida
Mammalian Genetics, National Cancer Institute