The Larimore Lab: a brief view behind the bench
It has been over a year now since joining the Larimore Lab after falling in love with the never-ending, ever-changing process that is research. Since then, my determination to pursue biomedical research as a career has only multiplied as I have thoroughly appreciated every second of my time being an investigator in and out of the lab. This post serves to showcase a bit about what we’ve been up to in the Larimore Lab the past year or so.
Endosomal Trafficking is disrupted in Neurodevelopmental Disorders
Previous work has indicated that endosomal trafficking is affected in both Rett syndrome (RTT) and schizophrenia (SZ), suggesting a common molecular mechanism that underlies the pathogenesis of these neurodevelopmental disorders. As a result, we hypothesized protein expression of key endosomal markers (EEA1, Rab11, LAMP1, AP3) is altered in RTT and SZ, contributing to the dendritic spine loss that is characteristic of these disorders.
I performed immunofluorescent staining on tissues from mutant mouse prefrontal cortices and hippocampal formations, brain regions affected in these disorders. Additionally, I conducted western blots using homogenates of whole-brain lysates and heavy synaptosomes, which is a neuronal structure composed of synaptic terminals where endosomal machinery is localized. Furthermore, I cultured PC12 cells for pulse-chase analyses to observe effects on trafficking. Working with other undergraduate students in the Larimore lab, we discovered altered endosomal markers, altered neurite outgrowth, and altered trafficking kinetics in models for RTT and SZ. These novel findings significantly implicate endosomal pathway dysfunction in RTT and SZ, potentially contributing to the cognitive deficits characteristic of these two neurodevelopmental disorders. I presented this work at four conferences including the 2019 Society for Neuroscience Conference and the 2019 Georgia Undergraduate Research Conference. My efforts performing the experiments, generating data sets, and creating figures culminated in a manuscript submitted for peer-review.