Neuroscience Graduate Program at UCSF
Genetics and genomics of developmental neuropsychiatric disorders
The State lab focuses on gene discovery in childhood neuropsychiatric and neurodevelopmental disorders and then on leveraging these findings to elaborate underlying pathophysiological mechanisms.
The State lab has a long standing interest in the identification of rare mutations contributing to childhood neurodevelopmental and neuropsychiatric disorders including autism, Tourette syndrome, brain malformations and, more recently, childhood onset Schizophrenia. We employ strategies ranging from traditional linkage analysis in unusual, highly informative pedigrees to high-throughput massively parallel sequencing of large cohorts. Our laboratory is also keenly interested in employing these genetic findings as a starting point to illuminate the biology underlying these conditions, with the ultimate goal of identifying novel treatment targets. In this regard, we undertake collaborations with a range of laboratories to investigate the neurobiological and systems biological consequences of the mutations we have identified.
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Ercan-Sencicek AG, Stillman AA, Ghosh Ak, Bilguvar K, O’Roak BJ, Mason CE, Abbott T, Gupta A, King RA, Pauls DL, Tischfield JA, Heiman GA, Singer HS, Gilbert DL, Hoekstra PJ, Morgan TM, Loring E, Yasuno K, Fernandex T, Sanders S, Louvi A, Cho JH, Mane S, Colangelo CM, Biederer T, Lifton RP, Gunel M, State MW (2010). L-histidine decarboxylase and Tourette’s syndrome. New England Journal of Medicine. 362(20):1901-1908. PMID: 20445167
Bilguvar K, Ozturk AK, Louvi A, Kwan, KY Choi M, Tatli B, Yalnizoglu D, Tuysuz B, Caglayan AO, Gokben S, Kaymakcalan H, Barak T, Bakircioglu M, Yasuno K, Ho W, Sanders S, Zhu Y, Yilmaz S, Dincer A, Johnson MH, Bronen RA, Kocer N, Per H, Mane S, Pamir MN, Yalcinkaya C, Kumandas S, Topcu M, Ozmen M, Sestan N, Lifton RP*, State MW*, Gunel M* (2010). Whole-exome sequencing identifies recessive WDR62 mutations in severe brain malformations. Nature. 467(7312):207-210. PMID: 20729831
Sanders SJ, Ercan-Sencicek AG, Hus V, Luo R, Murtha MT, Morenon-De-Luca D, Chu SH, Moreau MP, Gupta AR, Thomson SA, Mason CE, Bilguvar K, Celestino-Soper P, Choi M, Crawford EL, Davis L, Davis Wright NR, Dhodapkar RM, DiCola M, DiLullo NM, Fernandez TV, Fielding-Singh V, Fishman DO, Frahm S, Garagaloyan R, Goh GS, Kammela S, Klei L, Lowe JK, Lund SC, McGrew AD, Meyer KA, Moffat WJ, Murdoch JD, O’Roak BJ, Ober GT, Pottenger RS, Raubeson MJ, Song Y, Wang Q, Yaspan BL, Yu TW, Yurkiewicz IR, Beaudet AL, Cantor RM, Curland M, Grice DE, Gunel M, Lifton RP, Mane SM, Martin DM, Shaw CA, Sheldon M, Tischfield JA, Walsh CA, Morrow EM, Ledbetter DH, Fombonne E, Lord C, Martin CL, Brooks AI, Sutcliffe JS, Cook Jr. EH, Geschwind D, Roeder K, Devlin B, State MW (2011). Multiple recurrent de novo copy number variations (CNVs), including duplications of the 7q11.23 Williams-Beuren syndrome region, are strongly associated with autism. Neuron. 70(5):863-865. PMID 21658581
Novarino G, El-Fishawy P, Kayserili H, Meguid NA, Scott EM, Schroth J, Silhavy JL, Kara M, Khalil RO, Ben-Omran T, Ercan-Sencicek AG, Hashish AF, Sanders SJ, Gupta AR, Hashem HS, Matern D, Gabriel S, Sweetman L, Rahimi Y, Harris RA, State MW, Gleeson JG (2012). Mutations in BCKD-kinase Lead to a Potentially Treatable Form of Autism with Epilepsy. Science. 338(6105):394-7.
State MW, Sestan N. (2012). The emerging biology of Autism Spectrum Disorders. Science, 337:1301-1303
Sanders SJ, Murtha MT, Gupta AR, Murdoch JD, Raubeson MJ, Willsey AJ, Ercan-Sencicek AG, DiLullo NM, Parikshak NN, Stein JL, Walker MF, Ober GT, Teran NA, Song Y, El-Fishawy P, Murtha R, Choi M, Overton JD, Bjornson RD, Carrierio NJ, Meyer KA, Bilguvar K, Mane SM, Sestan N, Lifton RP, Günel M, Roeder K, Geschwind D, Devlin B, State MW. (2012). De novo point mutations revealed by whole-exome sequencing are strongly associated with Autism Spectrum Disorders. Nature. 485(7397):237-41. PMID:22495306