Research Interests:
Research in my laboratory is focused on understanding how the mammalian brain is assembled. We study fundamental mechanisms of brain development including neurogenesis, neuronal migration, and neuronal connectivity.
More than anything else, the complexity of our brain defines us as humans and separates us from other species. Brain development is genetically complex, as evidence by the fact that nearly half of all genes are expressed in the developing brain. However, this complexity provides an ideal genetic system in order to understand the roles of key genes during development in humans. We use families with inherited disorders of brain development to identify key genes, and then study the function, genetic and biochemical interactions of each of these genes using model systems.
Track(s):
Genetics
MCB
BMS Focus Areas:
Neurobiology
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Lancaster MA, Louie CM, Silhavy JL, Sintasath L, DeCambre M, Nigam
SK, Willert K, Gleeson JG. Impaired Wnt/beta-catenin signaling
disrupts adult renal homeostasis and leads to cystic kidney
ciliopathy. Nat Med. 2009 In press.
Bielas SL, Silhavy JL, Brancati F, Kisseleva MV, Al-Gazali L, Sztriha
L, Bayoumi RA, Zaki MS, Abdel-Aleem A, Rosti O, Kayserili H, Swistun
D, Scott LC, Bertini E, Boltshauser E, Fazzi E, Travaglini L, Field
SJ, Dallapiccola B, Majerus PW, Valente EM, Gleeson JG. Mutations in
the inositol polyphosphate-5-phosphatase E gene link phosphatidyl
inositol signaling to the ciliopathies. Nat Genet. 2009 In press.
Bielas SL, Serneo FF, Chechlacz M, Deerinck TJ, Perkins GA, Allen PB,
Ellisman MH, Gleeson JG. Spinophilin facilitates dephosphorylation of
doublecortin by PP1 to mediate microtubule bundling at the axonal
wrist. Cell. 2007 May 4;129(3):579-91
Valente EM, Silhavy JL, Brancati F, Barrano G, Krishnaswami SR,
Castori M, Lancaster MA, Boltshauser E, Boccone L, Al-Gazali L, Fazzi
E, Signorini S, Louie CM, Bellacchio E, Bertini E, Dallapiccola B,
Gleeson JG. Mutations in CEP290, encoding a centrosomal protein,
cause pleiotropic forms of Joubert syndrome. Nature Gen 2006 Jun;38
(6):623-5.
Koizumi H, Higginbotham H, Poon T, Tanaka T, Brinkman BC, Gleeson JG.
Doublecortin maintains bipolar shape and nuclear translocation during
migration in the adult forebrain. Nature Neurosci. 2006 Jun;9(6):779-86.
Koizumi H, Tanaka T, Gleeson JG. doublecortin-like kinase functions
with doublecortin in neuronal migration. Neuron 2006 Jan 5:49(1):55-66.
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