Projects
Creating an optimal closed-loop electrical stimulation strategy for treating chronic pain.
Although pain sensation is essential for survival, chronic pain can be an enormous burden to patients. Previous efforts to treat chronic pain with neuromodulation via electrical stimulation only show limited efficacy for these patients. This is perhaps because previous stimulation strategies have been open loop with constant stimulation parameters (i.e., pulse width, duration, etc). In this project, we strive to construct a model-based closed-loop stimulation strategy to bring the malfunctioning pain circuit to a normal state. This strategy will allow the controller to adapt to the system over time and result in higher efficacy. I have recently started working on this project. Please stay tuned for more work!
EEG biomarkers for SYNGAP1 +/- (Poster, Slides, Paper)
SynGAP is a protein that regulates the insertion of AMPA receptors to the post synaptic density for synaptic potentiation. Heterozygous mutation in SynGAP1 leads to a premature synaptic potentiation which results in disorders like sleep & intellectual disorders and epilepsy, and the need for reliable diagnosis and efficacious treatment is growing. In this project, I worked to characterize abnormal brain signals in animals with SYNGAP1 +/- disorder by analyzing their EEGs. We show that there is a dysregulated brain signal in the gamma frequency (35 – 50 Hz) during sleep in mice with SYNGAP1+/- even at young ages. The dysregulation was further aggravated by sleep deprivation, indicating abnormalities in sleep homeostasis. This work is valuable for reliable diagnosis and the development of novel therapeutics for the disorder. The poster is from the 2021 American Epilepsy Society, and the slides are from 2022 Pediatric Neurology Conference talk. While working on this project, I had the opportunity to write a short commentary of a paper on epileptogenesis that is relevant to the project (attached here as well).
The efficacy of Perampanel, an AMPA receptor antagonist, on SYNGAP1 +/- (Manuscript in progress).
As aforementioned, many patients with SynGAP1 +/- disorder suffer from intellectual disorder, sleep disorder, seizure, etc. This is because SynGAP regulates the insertion of AMPA receptors in post synaptic densities, and AMPA receptors strengthen the connectivity between neurons. Therefore, with the SYNGAP1 +/- mutation, there is abnormally increased AMPA receptors, which lead to prematurely potentiated synapses. We strive to alleviate the clinical symptoms (learning disorder, sleep disorder, etc) using Perampanel, an FDA-approved AMPA receptor antagonist, on patients or animals with SynGAP1 +/-.
Brain Acid Soluble Protein 1 as a high-affinity cocaine binding site (Paper, Slides)
Cocaine is known to be a strong stimulant that inhibits dopamine reuptake, which implies that cocaine binds to the dopamine transporter. This is somewhat contradicting if we consider that cocaine is a strong stimulant but a weak inhibitor of the dopamine transporter. This suggests that there can be a separate pathway on which cocaine exerts its power. We report that the brain acid soluble protein 1 is a high-affinity cocaine binding site, which opens the door for cocaine to be involved in a separate biochemical mechanism. The slides are from 2019 Undergraduate Research Symposium. The paper is from Proceedings of National Academy of Sciences in 2022.