Miriam H. Meisler, Ph.D.
Myron Levine Distinguished University Professor of Human Genetics
We are studying neurological disease mutations in genes encoding human voltage-
gated sodium channels and phosphoinositide metabolism. To examine the molecular
mechanisms of pathogenesis, we generate mouse models of specific human mutations.
We are screening patient populations to identify new disease mutations.
In related projects, we are cloning several new
mouse mutants, using genomic tools including human/mouse genomic sequence
comparisons to identify noncoding regulatory sequences.
Lenk GM, Ferguson CJ, Chow CY, Jin N, Jones JM, Grant AE, Zolov SN, Winters JJ, Giger RJ, Dowling JJ, Weisman LS and Meisler MH (2011) Rescue of neurodegeneration by transgenic expression of a pathogenic variant of FIG4 responsible for Charcot-Marie-Tooth Disease, PLOS Genetics, 7(6):e1002104162.
Freilich ER, Jones JM*, Reyes C, Meisler MH* and Pearl PL (2011) Novel SCN1A mutation in a patient with Malignant Migrating Partial Seizures of Infancy, Arch. Neurol. 68:665-671.
Nicholson G, Lenk GM, Reddel S, Grant AE, Towne CF, Ferguson CJ, Simpson E, Scheuerle A, Yasick M, Hoffman S, Blouin R, Brandt C, Coppola G, Biesecker LG for the NIH Intramural Sequencing Center, Batish SD and Meisler MH (2011) Distinctive genetic and clinical features of CMT4J, a severe neuropathy caused by mutations in the PI(3,5)P2 phosphatase FIG4. Brain 134: 1959-1971.
Ferguson C., Lenk G, Meisler MH (2009) Defective autophagy in neurons and astrocytes from mice deficient in PI(3,5)P2 Human Molecular Genetics 18: 4868-4878.
Sharkey LM, Xiaoyang Cheng, Valerie Drews, David A. Buchner, Julie M. Jones,Monica J. Justice, Stephen G. Waxman, Sulayman D. Dib-Hajj, and Miriam H. Meisler (2009). The ataxia3 Mutation in N-Terminal Cytoplasmic Domain of Sodium Channel Nav1.6 Disrupts Intracellular Trafficking. J. Neurosci.29:2733�2741.
Chow CY, Landers JE, Bergren SK, Sapp PC, Grant AE, Jones JM, Everett L, Lenk GM, McKenna-Yasek DM, Weisman LS, Figlewicz D, Brown RH, and Meisler MH (2009) Deleterious variants of FIG4, a phosphoinositide phosphatase, in patients with ALS. Am. J. Hum.Genet. 84:85-88.
Jin N, Chow CY, Liu L, Zolov SN, Bronson R, Davisson M, Petersen JL, Zhang Y, Park S, Duex JE, Goldowitz D, Meisler MH* and Weisman LS* (2008) VAC14 nucleates a protein complex that is essential for the regulation of PI(3,5)P2 levels in yeast and mouse. EMBO J. 27:3221-34. (*co-senior authors).
Drews VL, Shi K, de Haan G and Meisler MH (2007) Identification of evolutionarily conserved, functional noncoding elements in the promoter region of the sodium channel gene SCN8A. Mammalian Genome 18:723-31.
Howell VM, Jones JM, Bergren S, Li L, Billi AC, Avenarius MR and Meisler MH (2007) Evidence for a direct role of the disease modifier SCNM1 in splicing. Human Molecular Genetics 16:2506-2516.
Chow CY, ZhangY, Dowling J, Jin N, Adamska M, Shiga K, Szigeta K, Shy M, Li J, Zhang X, Lupski JR, Weisman L, Meisler MH (2007) Mutation of FIG4 causes neurodegeneration in the pale tremor mouse and patients with CMT type 4G. Nature 448:68-72.
Kearney JA, Wiste AK, Stephani U, Trudeau MM, Siegel A, RamachandranNair R, Elterman RD, Muhle H, Reinsdorf J, Shields WD, Meisler MH, Escayg A. (2006) Recurrent de novo mutations of SCN1A in severe myoclonic epilepsy of infancy. Pediatric Neurol. 34:116-120.
Levin SI, Aman TK, Khaliq ZM, Grieco TM, Woodruff-Pak DS, Raman IM and Meisler MH. (2006) Impaired motor function and learning in mice with conditional knockout of the Na channel Scn8a (NaV1.6) in cerebellar Purkinje neurons and granule cells. J. Neurophysiology 96:785-93. Epub 2006 May 10.
Trudeau MM, Dalton JC, Day JW, Ranum LP, Meisler MH. (2006) Heterozygosity for a protein truncation mutation of sodium channel SCN8A in a patient with cerebellar atrophy, ataxia and mental retardation. J Med Genet. 43:527-30. Epub 2005 Oct 19.
Schmitt-JohnT, Drepper C, Mu�mann A, Hahn P, Kuhlmann M, Thiel C, Hafner M, Lengeling A, Heimann P, Jones JM, Meisler MH, Jockusch H (2005) Mutation of Vps54 causes motor neuron disease and defective spermiogenesis in the wobbler mouse. Nature Genetics 37:1213-1215.