James Eubanks

Research Synopsis

The primary interests of my group relate to defining pathogenic mechanisms associated with rare X-linked genetic neurodevelopmental conditions, and testing new therapeutic strategies in different models of these specific conditions. Our group is currently investigating conditions such as Rett syndrome (caused by mutations of the MECP2 gene), CDKL5 Deficiency Disorder (caused by mutations of the CDKL5 gene), and Bain syndrome (caused by mutations of the HNRNPH2 gene). The generation of models for additional conditions, including a rare epileptic encephalopathy (caused by mutations of the PIGA gene) are in development.  We employ both cell culture and mouse models of these conditions to define how specific mutations of the respective causal genes alter normal brain function and/or alters the normal progression of brain development. In the mouse models, we employ behavioural interrogations, electrocorticography and electroencephalography, as well as in vivo and in vitro electrophysiology. In both mouse and cell culture systems, we use molecular, cell biological, pharmacological, and biochemical techniques to identify alterations in mRNA / protein levels and / or signaling pathways that arise from the specific mutation. From these observations we then test rationale-based strategies as first-line attempts to correct the observed alterations. Our studies also generate novel transgenic mouse lines that can be used to address questions relating to our focus, and partners these studies with the testing of novel pharmacological agents as part of translational efforts.  We are well positioned to assess therapeutically meaningful endpoints for the translational studies, and have the skills needed to identify key deficits that can then be subsequently targeted. It is our intention to identify novel strategies that can someday be employed to treat patients with these conditions, with the ultimate goal being condition correction.