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Séminaire - Peter Penzes Synaptic biology of neurodevelopmental disorder risk factors

Abstract :

Recent large-scale human genomics studies have identified a plethora of molecules contributing to neurodevelopmental disorder risk. However, the significance of these findings for pathogenesis remains to be clarified, because the biological functions of many such risk molecules are not known. Genomics, combined with neuropathological studies, point to synapses are key cellular substrates in intellectual disability, autism, schizophrenia, and bipolar disease. Research in my lab aims to decipher the synaptic functions of neurodevelopmental disorder risk factors in hopes of understanding their roles in the pathogenesis. I will present our recent findings employing molecular and imaging approaches to uncover novel synaptic functions of molecular networks centered around ankyrin-G, encoded by the ANK3 gene, a major risk gene for intellectual disability, autism, schizophrenia, and bipolar disorder.

 

Selected publications

Blizinsky KD, Diaz-Castro B, Forrest MP, Schürmann B, Bach AP, Martin-de-Saavedra MD, Wang L, Csernansky JG, Duan J, Penzes P. Reversal of dendritic phenotypes in 16p11.2 microduplication mouse model neurons by pharmacological targeting of a network hub. Proc Natl Acad Sci U S A. 2016 Jul 26;113(30):8520-5.

Smith KR, Kopeikina KJ, Fawcett-Patel JM, Leaderbrand K, Gao R, Schürmann B, Myczek K, Radulovic J, Swanson GT, Penzes P. Psychiatric risk factor ANK3/ankyrin-G nanodomains regulate the structure and function of glutamatergic synapses. Neuron. 2014 Oct 22;84(2):399-415.

Russell TA, Blizinsky KD, Cobia DJ, Cahill ME, Xie Z, Sweet RA, Duan J, Gejman PV, Wang L, Csernansky JG, Penzes P. A sequence variant in human KALRN impairs protein function and coincides with reduced cortical thickness. Nat Commun. 2014 Sep 16;5:4858.

 Penzes P, Cahill ME, Jones KA, VanLeeuwen JE, Woolfrey KM. Dendritic spine pathology in neuropsychiatric disorders. Nat Neurosci. 2011 Mar;14(3):285-93.