Mark S. LeDoux, M.D., Ph.D.

Mark S. LeDoux, M.D., Ph.D.

Professor
Department of Neurology Department of Anatomy and Neurobiology

Chief
Division of Movement Disorders

Director
Dystonia and Huntington Disease Clinics

Director
Movement Disorders Research Laboratories


The University of Tennessee Health Science Center
855 Monroe Avenue
Suite 415 Link Building
Memphis, TN 38163
Phone: (901) 448-1662
Fax: (901) 448-7440
Email: Mark S. LeDoux

 

Education

  • M.D. Institution: Louisiana State University School of Medicine
  • Ph.D. Institution: University of Alabama, Birmingham, Department of Neuroscience
  • Residency Training: University of Alabama at Birmingham; University of Tennessee Health Science Center

Links

Research Interests

  • Genetics and pathobiology of primary dystonia
    • Using vertebrate and invertebrate models, human lymphoblastoid and fibroblast cell lines, and stable transfected cell lines, we study the cellular and systems biology of dystonia-associated proteins.
    • Genetic contributions to late-onset primary dystonia are being examined with whole-exome and whole genome sequencing with integrated linkage analysis and RNA-seq. We also utilize candidate gene, genome-wide association and whole-genome gene expression studies.
  • Mechanisms of neurodegeneration in Parkinson disease: several members of the tetrahydroisoquinoline (TIQ) family of monoamine alkaloids can be formed from dopamine or its oxidized metabolites and may be involved in the pathogenesis of monoaminergic cell death in Parkinson disease. To examine the potential role of TIQs in monoaminergic cell death, we have used enantiomeric-selective high-performance liquid chromatography with electrochemical detection, liquid chromatography with tandem mass spectroscopy, cell culture studies of neurotoxicity and assays of mitochondrial membrane potential.
  • Clinical trials of therapeutic interventions for movement disorders (dystonia, Huntington disease, Parkinson disease, restless legs syndrome)
  • Anatomy and computational organization of motor systems
    • The neural networks mediating suprasegmental control of the blink reflex and spontaneous blinking remain poorly understood. Viral transneuronal tracing is being used to define the integrated premotor cortical and subcortical control of levator palpebrae and orbicularis oculi motoneuron activity.
    • In isolation or via interactions with striatal-thalamo-cortical pathways, olivocerebellar structures play a critical role in disorders of motor control such as ataxia and dystonia. Using neurophysiological and molecular tools, we are dissecting the relative roles of individual network elements in the positive and negative signs characteristic of individual movement disorders.

Clinical Subspecialty Expertise

Adult and Pediatric Movement Disorders, Botulinum Toxin for Dystonia and Spasticity, Deep Brain Stimulation

Representative Publications

  • Tian J, Vemula SR, Xiao J, Valente EM, Defazio G, Petrucci S, Gigante AF, Rudzińska-Bar M, Wszolek ZK, Kennelly KD, Uitti RJ, van Gerpen JA, Hedera P, Trimble EJ, LeDoux MS. Whole-exome sequencing for variant discovery in blepharospasm. Mol Genet Genomic Med. 2018 May 16. doi: 10.1002/mgg3.411. [Epub ahead of print] PubMed PMID: 29770609.
  • Toro C, Hori RT, Malicdan MCV, Tifft CJ, Goldstein A, Gahl WA, Adams DR, Fauni HB, Wolfe LA, Xiao J, Khan MM, Tian J, Hope KA, Reiter LT, Tremblay MG, Moss T, Franks AL, Balak C; C4RCD Research Group, LeDoux MS. A recurrent de novo missense mutation in UBTF causes developmental neuroregression. Hum Mol Genet. 2018 Apr 1;27(7):1310. doi: 10.1093/hmg/ddy049. PubMed PMID: 29447355.
  • Toro C, Hori RT, Malicdan MCV, Tifft CJ, Goldstein A, Gahl WA, Adams DR, Harper F, Wolfe LA, Xiao J, Khan MM, Tian J, Hope KA, Reiter LT, Tremblay MG, Moss T, Franks AL, Balak C; C4RCD Research Group, LeDoux MS. A recurrent de novo missense mutation in UBTF causes developmental neuroregression. Hum Mol Genet. 2018 Feb 15;27(4):691-705. doi: 10.1093/hmg/ddx435. PubMed PMID: 29300972; PubMed Central PMCID: PMC5886272.
  • Khan MM, Xiao J, Patel D, LeDoux MS. DNA damage and neurodegenerative phenotypes in aged Ciz1 null mice. Neurobiol Aging. 2018 Feb;62:180-190. doi: 10.1016/j.neurobiolaging.2017.10.014. PubMed PMID: 29154038; PubMed Central PMCID: PMC5877805.
  • Hope KA, LeDoux MS, Reiter LT. Glial overexpression of Dube3a causes seizures and synaptic impairments in Drosophila concomitant with down regulation of the Na(+)/K(+) pump ATPα. Neurobiol Dis. 2017 Dec;108:238-248. doi: 10.1016/j.nbd.2017.09.003. Epub 2017 Sep 6. PubMed PMID: 28888970; PubMed Central PMCID: PMC5675773.
  • Fernandez HH, Factor SA, Hauser RA, Jimenez-Shahed J, Ondo WG, Jarskog LF, Meltzer HY, Woods SW, Bega D, LeDoux MS, Shprecher DR, Davis C, Davis MD, Stamler D, Anderson KE. Randomized controlled trial of deutetrabenazine for tardive dyskinesia: The ARM-TD study. Neurology. 2017 May 23;88(21):2003-2010. doi: 10.1212/WNL.0000000000003960. Epub 2017 Apr 26. PubMed PMID: 28446646; PubMed Central PMCID: PMC5440239.

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