Medical Scientist Training Program    Back to Main

Faculty Detail    
Campus Address SHEL 914 Zip 2182
Phone  (205) 975-5573
Other websites

Faculty Appointment(s)
Appointment Type Department Division Rank
Center  Comprehensive Cancer Center  Comprehensive Cancer Center Associate Professor
Center  General Clinical Research Center  Comprehensive Neuroscience Center Associate Professor
Center  Neurology   Ctr Neurodegeneration & Exp Ther (CNET) Associate Professor
Center  Neurology   Evelyn F. McKnight Brain Institute Associate Professor
Center  GL Ctr for Craniofacial, Oral, & Dental Disorders  GL Ctr for Craniofacial, Oral, & Dental Disorders Associate Professor
Center  Civitan International Research Center  Civitan International Research Center Associate Professor
Center  Ctr for Glial Bio in Med  Ctr for Glial Bio in Med Associate Professor
Primary  Neurobiology  Neurobiology Associate Professor
Secondary  Biochemistry & Molecular Genetics  Biochemistry & Molecular Genetics Associate Professor
Secondary  Genetics   Genetic & Translational Med Assistant Professor

Graduate Biomedical Sciences Affiliations
Biochemistry and Molecular Genetics Program 
Cell, Molecular, & Developmental Biology 
Cellular and Molecular Biology Program 
Genetics, Genomics and Bioinformatics 
Integrative Genetics Graduate Program 
Medical Scientist Training Program 

Biographical Sketch 
He is an Associate Professor in the Department of Neurobiology at the University of Alabama at Birmingham. He was an undergraduate at the University of South Florida and then went on to the University of Florida as a graduate student under the supervision of Maurice Swanson. During his studies with Dr. Swanson, he biochemically isolated the first family of heterogeneous nuclear ribonuclear proteins in yeast and performed classical genetics to investigate the function of hnRNPs in yeast. He then began his training in mouse genetics in the laboratory of Drs. Neal Copeland and Nancy Jenkins at the National Cancer Institute as a postdoctoral fellow. While at the NCI he used a positional cloning approach to identify the mouse mutations ashen, waltzer and ataxia. The identification of these gene products has allowed for important insights into vesicular trafficking, auditory function, and neurodegeneration respectively. In addition to these projects, he also studied the function of voltage gated calcium channels by generating gene knockouts for the alpha1A and alpha1E subunits in mice. He joined the faculty at UAB in 2002 to continue his studies on the nervous system using mouse models of neurodegeneration.

Research/Clinical Interest
Mouse Models of Neurodegeneration
The identification of genes involved in neurodegeneration is a powerful means to understand the mechanisms of neuronal cell loss. Our laboratory focuses on identifying these genes through a variety of approaches in mice that include transgenics, gene-knockouts and positional cloning. We have recently cloned the mouse neurological mutation ataxia. The ataxia mouse displays a severe tremor and hind limb paralysis by 5 weeks of age. We showed that ataxia gene encodes Usp14, a member of the ubiquitin/proteosomepathway. During our analysis of the ataxia mouse, we found that loss of Usp14 results in synaptic transmission defects in both the central and peripherial nervous sytem. Since the members of this pathway act on a variety of substrates, we believe that the identification of the substrate(s) for Usp14 will provide important insights into the pathogenesis of the ataxia tremor and paralysis. In addition to Usp14, we are also investigating the function of several other members of the ubiquitin/proteosome pathway that are involved in neuronal function. The mouse waltzer mutation is another mutation that we recently cloned. The waltzer gene encodes Cdh23, the newest member of the cadherin superfamily. Loss of this gene product in humans results in both auditory and vestibular dysfunction. We are currently producing antibodies and generating other alleles of Cdh23 to understand how this gene product functions in the perception of sound and maintenance of balance.

Selected Publications 
Publication PUBMEDID
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  24218545 
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.  24358326 
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  24358326 
Wilson, S.M., Yip, R., Swing, D.A., O'Sullivan, T.N., Zhang, Y., Novak, E.K., Swank, R.T., Russell, L.B., Copeland, N.G., and Jenkins, N.A. 2000. A mutation in Rab27a causes the vesicle transport defects observed in ashen mice. Proc. Natl. Acad. Sci. USA 97:7933-7938.  10859366 
Wilson, S.M., Toth, P.T., Oh, S.B., Gillard, S.E., Volsen, S., Ren, D., Philipson, L.H., Lee, E.C., Fletcher, C.F., Tessarollo, L., Copeland, N.G., Jenkins, N.A., and Miller, R.J.  2000.  The status of voltage-dependent calcium channels in µ1E knock-out mice.  J. Neurosci. 20:8566-8571.  11102459 
Fletcher, C.F., Tottene, A., Lennon, V.A., Wilson, S.M., Dubel, S.J., Paylor, R., Hosford, D.A., Tessarollo, L., McEnery, M.W., Pietrobon, D., Copeland, N.G., and Jenkins, N.A.  2001.  Dystonia and cerebellar atrophy in Cacna1a null mice lacking P/Q calcium channel activity.  FASEB J.  15:1288-1290.  11344116 
Wilson, S.M., Householder, D.B., Coppola, V., Tessarollo, L., Fritzsch, B., Lee, E.C., Goss, D., Carlson, G.A., Copeland, N.G., and Jenkins, N.A.  2001.  Mutations in Cdh23 cause nonsyndromic hearing loss in waltzer mice.  Genomics  74:228-233.   11386759 
Wilson, S.M., Bhattacharyya, B., Rachel, R.A., Coppola, V., Tessarollo, L., Householder, D.B., Fletcher, C.F., Miller, R.J., Copeland, N.G., and Jenkins, N.A. 2002. Synaptic defects in ataxia mice result from a mutation in Usp14, a ubiquitin-specific protease. Nature Genetics 32:420-425.  12368914 
Miller, R.M. and Wilson S.W. 2003. Neurological disease: UPS stops delivering! Trends Pharmacol. Sci. 24:18-23.  12498726 
Anderson C, Crimmins S, Wilson JA, Korbel GA, Ploegh HL, Wilson SM. 2005. Loss of Usp14 results in reduced levels of ubiquitin in ataxia mice. J Neurochem. 2005 Nov;95(3):724-31  16190881 
Crimmins S, Jin Y, Wheeler C, Huffman AK, Chapman C, Dobrunz LE, Levey A, Roth KA, Wilson JA, Wilson SM. 2006. Transgenic rescue of ataxia mice with neuronal-specific expression of ubiquitin-specific protease 14. J Neurosci. 26(44):11423-31  17079671 
Walters BJ, Campbell SL, Chen PC, Taylor AP, Schroeder DG, Dobrunz LE, Artavanis-Tsakonas K, Ploegh HL, Wilson JA, Cox GA, Wilson SM. 2008. Differential effects of Usp14 and Uch-L1 on the ubiquitin proteasome system and synaptic activity. Mol Cell Neurosci. 39(4):539-48.  18771733 
Crimmins S, Sutovsky M, Chen PC, Huffman A, Wheeler C, Swing DA, Roth K, Wilson J, Sutovsky P, Wilson S. 2009. Transgenic rescue of ataxia mice reveals a male-specific sterility defect. Dev Biol. 325(1):33-42.  18926813 
Qiao L, Hamamichi S, Caldwell KA, Caldwell GA, Yacoubian TA, Wilson S, Xie ZL, Speake LD, Parks R, Crabtree D, Liang Q, Crimmins S, Schneider L, Uchiyama Y, Iwatsubo T, Zhou Y, Peng L, Lu Y, Standaert DG, Walls KC, Shacka JJ, Roth KA, Zhang J. Lysosomal enzyme cathepsin D protects against alpha-synuclein aggregation and toxicity. Mol Brain. 2008 Nov 21;1:17. doi: 10.1186/1756-6606-1-17  19021916 
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.  19535597 
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.  19726649 
Lappe-Siefke C, Loebrich S, Hevers W, Waidmann OB, Schweizer M, Fehr S, Fritschy JM, Dikic I, Eilers J, Wilson SM, Kneussel M. The ataxia (axJ) mutation causes abnormal GABAA receptor turnover in mice. PLoS Genet. 2009 Sep;5(9):e1000631  19759851 
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.  20829789 
Bhattacharyya BJ, Wilson SM, Jung H, Miller RJ. 2011. Altered neurotransmitter release machinery in mice deficient for the de-ubiquitinating enzyme, Usp14. Am J Physiol Cell Physiol. Nov 9  22075695 
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  22131412  
Jin YN, Chen PC, Watson JA, Walters BJ, Phillips SE, Green K, Schmidt R, Wilson JA, Johnson GV, Roberson ED, Dobrunz LE, Wilson SM. Usp14 Deficiency Increases Tau Phosphorylation without Altering Tau Degradation or Causing Tau-Dependent Deficits. PLoS One. 2012;7(10) Epub 2012 Oct 29.  23144711 
Hallengren J, Chen PC, Wilson SM. 2013.Neuronal Ubiquitin Homeostasis. Cell Biochem Biophys. 2013 May 18.  23686613 
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  25575639 
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.  25954152 
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.  26115514 
Neurotoxic mechanisms by which the USP14 inhibitor IU1 depletes ubiquitinated proteins and Tau in rat cerebral cortical neurons: Relevance to Alzheimer's disease.
Kiprowska MJ, Stepanova A, Todaro DR, Galkin A, Haas A, Wilson SM, Figueiredo-Pereira ME.
Biochim Biophys Acta Mol Basis Dis. 2017 Jun;1863(6):1157-1170. doi: 10.1016/j.bbadis.2017.03.017. Epub 2017 Apr 1. 
Chronic over-expression of ubiquitin impairs learning, reduces synaptic plasticity, and enhances GRIA receptor turnover in mice.
Vaden JH, Tian T, Golf S, McLean JW, Wilson JA, Wilson SM.
J Neurochem. 2019 Feb;148(3):386-399. doi: 10.1111/jnc.14630. Epub 2018 Dec 10.