ORCID ID: 0000-0002-0759-0272
Huang Z, Khaled HG, Kircshmann M, Gobes SMH, Hahnloser RHR. Excitatory and inhibitory synapse reorganization immediately after critical sensory experience in a vocal learner. eLife. 2018 October 25. doi: 10.7554/eLife.37571
In the lab of Dr. Gobes at Wellesley College, I studied the dynamic mechanisms involved in learning and memory acquisition in zebra finches. When I joined the lab, we had received a large dataset from our collaborator comprised of high resolution electron microscopy images of HVC (proper name), a nucleus of the songbird brain circuity, obtained at different stages of learning. While only comparisons of synapse numbers between experimental groups had been made at the time, I determined that changes in synapse morphology such as size and curvature also occur in response to sensory experience during learning. These results suggest a model for song learning in which structural imbalance of excitation and inhibition, represented by changes in both synapse numbers and morphologies, form a foundation for song memorization. This model could potentially be generalized to other modes of learning via sensory exposure, providing greater insight into how experience shapes brain structure to enable memory formation.
Khaled HG, Feng H, Hu X, Sun X, Zheng W, Li PP, Rudnicki DD, Ye W, Chen YC, Southall N, Marugan J, Ross CA, Ferrer M, Henderson MJ, Margolis RL. Scientific Reports. 2021 March 17. doi: 10.1038/s41598-021-85279-2
In the lab of Dr. Margolis at Johns Hopkins School of Medicine, I collaborated with the National Center for Advancing Translational Sciences (NCATS) on a high-throughput screen (HTS) for small molecules therapeutics for Huntington’s Disease (HD). 52,041 compounds were tested for their ability to suppress huntingtin expression via modulation of huntingtin or huntingtin antisense promoter activity. I assisted with assay design, strategy, and analysis, and conducted additional validation experiments. 898 replicable hits were identified in the promoter screen, and 14 compounds were shown to lower huntingtin protein at nontoxic doses in either HEK298 or HD patient derived lymphoblast cell lines, as measured by ATP-based cytotoxicity assays. However, all efficacious compounds tested in neurons were found to be cytotoxic in those cell lines by cell-count based toxicity measurements. Our results suggest that ATP-based cytoxicity assays (ex. CellTiter-Glo), while convenient for HTS, may be insufficient for screening out cytotoxic compounds, particularly when screening for suppression of protein expression.