James Eubanks

The primary interests of Dr. Eubanks' 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. The 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.  The group employs 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, the group employs behavioural interrogations, electrocorticography and electroencephalography, as well as in vivo and in vitro electrophysiology. In both mouse and cell culture systems, the group uses 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. The group's 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.  The group is 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 the group's intention to identify novel strategies that can someday be employed to treat patients with these conditions, with the ultimate goal being condition correction.

Select Publications

1. Liu H, Tufa U, Zahra A, Chow J, Sivanenthiran N, Cheng C, Liu Y, Cheung P, Lim S, Jin Y, Mao M, Sun Y, Wu C, Wennberg R, Bardakjian B, Carlen PL, Eubanks JH, Song H, & Zhang L (2021) Electrographic Features of Spontaneous Recurrent Seizures in a Mouse Model of Extended Hippocampal Kindling. Cerebral Cortex Communication 2:tgab004
2. Shulyakova N, Andreazza AC, Mills LR, Eubanks JH. (2017) Mitochondrial Dysfunction in the Pathogenesis of Rett Syndrome: Implications for Mitochondria-Targeted Therapies. Front Cell Neurosci. 11:58.
3. Zhang L, Wither RG, Lang M, Wu C, Sidorova-Darmos E, Netchev H, Matolcsy CB, Snead OC, Eubanks JH. (2016) A Role for Diminished GABA Transporter Activity in the Cortical Discharge Phenotype of MeCP2-Deficient Mice. Neuropsychopharmacology. 41:1467-76. PMID: 26499511
4. Lang M, Wither RG, Colic S, Wu C, Monnier PP, Bardakjian BL, Zhang L, Eubanks JH. (2014) Rescue of behavioral and EEG deficits in male and female Mecp2-deficient mice by delayed Mecp2 gene reactivation. Hum Mol Genet. 23:303-18. PMID: 24009314
5. Lang M, Wither RG, Brotchie JM, Wu C, Zhang L, Eubanks JH (2013) Selective preservation of MeCP2 in catecholaminergic cells is sufficient to improve the behavioral phenotype of male and female Mecp2-deficient mice. Hum Mol Genet. 22:358-71. PMID: 23077217
6. Katz DM, Berger-Sweeney JE, Eubanks JH, Justice MJ, Neul JL, Pozzo-Miller L, Blue ME, Christian D, Crawley JN, Giustetto M, Guy J, Howell CJ, Kron M, Nelson SB, Samaco RC, Schaevitz LR, St Hillaire-Clarke C, Young JL, Zoghbi HY, Mamounas LA. (2012) Preclinical research in Rett syndrome: setting the foundation for translational success. Dis Model Mech. 5:733-45.
7. Xie W, Barr CL, Kim A, Yue F, Lee AY, Eubanks J, Dempster EL, Ren B. (2012) Base-resolution analyses of sequence and parent-of-origin dependent DNA methylation in the mouse genome. Cell. 148:816-31. PMID: 22341451
8. D'Cruz JA, Wu C, Zahid T, El-Hayek Y, Zhang L, Eubanks JH. (2010) Alterations of cortical and hippocampal EEG activity in MeCP2-deficient mice. Neurobiol Dis. 38:8-16. PMID: 20045053
9. Jugloff DG, Vandamme K, Logan R, Visanji NP, Brotchie JM, Eubanks JH. (2008) Targeted delivery of an Mecp2 transgene to forebrain neurons improves the behavior of female Mecp2-deficient mice. Hum Mol Genet. 17:1386-96. PMID: 18223199
10. Zhang L, He J, Jugloff DG, Eubanks JH. (2008) The MeCP2-null mouse hippocampus displays altered basal inhibitory rhythms and is prone to hyperexcitability. Hippocampus. 18:294-309.  PMID: 18058824
11. Asaka Y, Jugloff DG, Zhang L, Eubanks JH, Fitzsimonds RM. (2006) Hippocampal synaptic plasticity is Impaired in the Mecp2-null mouse model of Rett syndrome. Neurobiol Dis. 21:217-27. PMID: 16087343
12. Jugloff DG, Jung BP, Purushotham D, Logan R, Eubanks JH. (2005) Increased dendritic complexity and axonal length in cultured mouse cortical neurons overexpressing methyl-CpG-binding protein MeCP2. Neurobiol Dis. 19:18-27.
13. Jung BP, Jugloff DG, Zhang G, Logan R, Brown S, Eubanks JH. (2003) The expression of methyl CpG binding factor MeCP2 correlates with cellular differentiation in the developing rat brain and in cultured cells. J Neurobiol. 55:86-96.

Appointments

• Department of Pharmacology & Toxicology
• Department of Physiology                         
• Department of Surgery
• Krembil Research Institute
• Institute of Medical Sciences