Miriam H. Meisler, Ph.D.
Myron Levine Distinguished University Professor
Professor of Human Genetics
Professor of Neurology
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.
Baulac S, Lenk GM, Dufresnois B, Bencheikh BOA, Couarch P, Renard R, Larson PA, Ferguson CJ, Noé E, Poirier K, Hubans C, Ferreira S, Guerrini R, Ouazzani R, El Hachimi KH, Meisler MH and Leguern L (2014) Role of phosphoinositide phosphatase FIG4 gene in familial epilepsy with polymicrogyria. Neurology. In press.
Lenk GM and Meisler MH, (2014). Mouse models of PI(3,5)P2 deficiency with impaired lysosome function. Methods in Enzymology 534:245-260.
Meisler MH, Grant AE, Jones JM, Lenk GM, He F, Todd PK, Kamali M, Albin RL, Lieberman AP, Langenecker SA and McInnis MG (2013) C9ORF72 expansion in a family with bipolar disorder. Bipolar Disorders15:326-332.
Campeau PM, Lenk GM, Lu JT, Bae Y, Burrage L, Turnpenny P, Corona Rivera JR, Morandi L, Mora M, Tuetter H, Vulto-van Silfhout AT, Faivre L, Haan E, Gibbs RA, Meisler MH and Lee BH (2013) Yunis-Varón syndrome is caused by mutations in FIG4 encoding a phosphoinositide phosphatase. Am. J. Hum. Genet. 92:781-791.
Jones JM, Meisler MH (2013) Modeling human epilepsy by TALEN targeting of mouse Scn8a. Genesis Nov 28. doi: 10.1002/dvg.22731. [Epub ahead of print]
O’Brien JE and Meisler MH (2013) Sodium channel SCN8A (Nav1.6): properties and de novo mutations in epileptic encephalopathy and intellectual disability. Frontiers in Genetics 4: 213.
Veeramah KR, O’Brien JE, Meisler MH, Cheng X, Dib-hajj SD, Waxman SG, Talwar D, Girirajan S, Eichler EE, Restifo LL, Erickson RP, Hammer MF (2012) De novo pathogenic mutation of SCN8A identified by whole genome sequencing of a family quartet with infantile epileptic encephalopathy and SUDEP. Am. J. Hum. Genet. 90:502-510. PMC3309181
O'Brien JE, Sharkey SM, Vallianatos CN, Blossom JC, Han C, Yu, T, Dib-Hajj, SD, Waxman SG and Meisler MH, Interaction of voltage-gated sodium channel Nav1.6 (SCN8A) with microtubule associated protein Map1b. (2012) J. Biol. Chem. 287:18459-66. PMC3365756
Need AC, Shashi V, Hitomi Y, Schoch K, Shianna KV, Meisler MH and Goldstein DB (2012) Clinical Application of Exome Sequencing in Unidentified Genetic Conditions, J. Med Genet. 49:353-61. PMC3375064
Ferguson CJ, Lenk GM, Jones JM, Grant AE, Winters JJ, Dowling JJ, Giger RJ and Meisler MH (2012) Neuronal expression of Fig4 is necessary and sufficient to prevent spongiform neurodegeneration, Human Molecular Genetics 21: 3525- 3534. PMC3406753
Lenk GM, Ferguson CJ, Chow CY, Jin N, Jones JM, Grant AE, Zolov SN, Winters
JJ, Giger RJ, Dowling JJ, Weisman LS, Meisler MH. Pathogenic mechanism of the FIG4 mutation responsible for Charcot-Marie-Tooth disease CMT4J. PLoS Genet. 2011Jun;7(6):e1002104. PMC310719
*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.
Winters JJ*, Ferguson CJ*, Lenk GM, Giger-Mateeva VI, Shrager P, Meisler MH and Giger RJ (2011) Congenital CNS hypomyelination and reduced number of mature oligodendrocytes in the Fig4 null mouse. J. Neurosci, 31:17736-17751. *co-first authors http://www.jneurosci.org/content/31/48/17736.long
O'Brien JE, Drews VL, Jones JM, Dugas JC, Barres BA and Meisler MH (2011) RBFOX proteins regulate alternative splicing of neuronal sodium channel SCN8A. Molec. Cell. Neurosci. 49:120-126. PMC3278527