2020 Senior Honor Thesis
While I initially envisioned my senior year living in the lab running experiments, I am still excited to work through my research thesis from home in El Paso, Texas (minus the data for now, of course). I am hopeful for the spring semester that students will be able to return safely to Agnes Scott’s campus. In the meantime, during this fall semester, I am currently drafting all but the Results and Discussion/Conclusion sections of my thesis paper. This independent research project of mine is a continuation of the endosomal trafficking research I have been conducting in the Larimore Lab since the summer of 2019.
Sphingolipid Metabolism in Rett Syndrome and Schizophrenia
While investigating endosomal trafficking in Rett syndrome (RTT) and schizophrenia (SZ) using mouse models and cell lines, our lab concluded that endosomal cargo is mis-trafficked in said neurodevelopmental disorders. Our study found increased expression of LAMP1, an endosomal marker for late endosomes and lysosomes, in RTT and SZ mouse brain tissue. Given that increased LAMP1 has been shown to cause aggregation of late endosomes and lysosomes, thereby resulting in an accumulation of cellular waste, there may also be metabolic dysfunction at the cellular level in RTT and SZ individuals. Previous clinical studies have found a significant accumulation of sphingolipid metabolites in individuals with RTT and SZ. Additionally, with sphingolipids being the most abundant lipid in brain tissue and with the lysosome playing an important role in the sphingolipid metabolic network, an investigation into the efficacy of the sphingomyelin pathway in RTT and SZ would be promising. I hypothesize there is dysfunction within the sphingolipid metabolic network in brain tissue of RTT and SZ model mice as a result of late endosomal/lysosomal aggregation and subsequent cellular waste accumulation.
Credit: “RTT mouse cortex stained for LAMP1 protein” by Alexandra Lombardo is licensed under CC BY NC 4.0