Jay English – NIH Trainee 2022-2024
Research progress:
I am a PhD student working in the lab of ChangHui Pak. I have developed skills in electrophysiology, including patch-clamp and High-Density Multi Electrode Array recording. My research focuses on the molecular mechanisms of autism spectrum disorders, with a particular focus on synaptic signaling and aberrant splicing. I utilize patient-derived induced pluripotent stem cells (iPSCs) along with engineered iPSCs differentiated into cortical glutamatergic and GABAergic induced neurons (iNs) and co-cultured to study synaptic activity with the goal of elucidating synpatopathic mechanisms of these disorders. I have made tremendous progress on my project, which is near completion and in preparation for publication.
I have characterized synaptic signaling in three patient-derived mixed iN cultures and have found an increase in spontaneous excitatory postsynaptic currents (sEPSCs) and a decrease in spontaneous inhibitory postsynaptic currents (sIPSCs) in the patient lines compared to three paired control lines. I’ve also found altered sodium channel activity in this system, which may lead to a translational aim in my project. I have derived a means of analyzing spontaneous network activity with the presence of microcircuits found in mixed cultures, and have found key differences in synchronous activity in these cultures. I have refined a technique for probing homeostatic plasticity, and am currently gathering this data alongside miniature postsynaptic currents to confirm our spontaneous findings and form a model to explain the discrepancies observed.
Publications:
P Dawes, M Smullen, A Fernandez-Fontaine, Yucheng Zhang, Jay English, Mohammed Uddin, ChangHui Pak, George M Church, Yingleong Chan, Elaine T Lim. Human Genetics 142(8). August 2023. DOI: 10.1007/s00439-023-02534-4
Jay English, Danny McSweeney, Ethan Howell, Fumiko Ribbe, ChangHui Pak. Methods in Molecular Biology series, Springer Nature August 2023. DOI: 10.1007/978-1-0716-3287-1_3
Danny McSweeney, Jay English, Ethan Howell, Fumiko Ribbe, ChangHui Pak. Methods in Molecular Biology series, Springer Nature August 2023. DOI: 10.1007/978-1-0716-3287-1_19