Eric Garcia

Eric Garcia, a senior neuroscience major at Pomona College, identified genes associated with Alzheimer’s Disease through differential expression analysis using RStudio statistical software.

Alzheimer’s Disease (AD) is a neurodegenerative disease characterized by cognitive impairments to memory, language, and visuospatial orientation. On a molecular level, AD pathogenesis is largely driven by amyloid beta (Aβ) plaques which disrupt neuronal communication. Aβ is a protein involved in neural growth; however, overaccumulation of Aβ can lead to the formation of plaques.

BSRP has been instrumental in my development as a young scientist, teaching me valuable skills in scientific communication, graduate school preparation, and networking. I’m very grateful to be a part of a group of such amazing peers, and have been so inspired by the collaborative nature of scientists at the Broad. Although this was my first time doing computational research, I always felt supported by my fellow Broadies, and look forward to exploring more opportunities in computational neuroscience in the future. I hope to pursue a PhD in neuroscience within the next few years, and am excited to see the incredible things that my fellow BSRP cohort goes on to accomplish! One of the genes known to be involved in AD risk is known as the triggering receptor expressed in myeloid cells 2, also known as TREM-2. In the central nervous system, TREM-2 is specifically expressed in microglia, which play an active role in regulating Aβ. Previous studies have suggested that loss of function mutations in TREM2 result in disease-state microglia unable to regulate Aβ, leading to Aβ plaque formation.

In this study, we identified genes associated with TREM-2 expression using the Cancer Cell Line Encyclopedia (CCLE), a database composed of gene expression data for human cancer cell lines. As the molecular pathways underlying AD are conserved across cell lines, the rich gene expression data in the CCLE represents a useful tool in studying AD. Through differential expression analysis in RStudio statistical software, we concluded that AZU1, PRTN3, MPO, ELANE, and TYROBP are all significantly associated with TREM-2 expression. While these genes are all individually known to be linked to AD, the connection between these genes have not been previously shown in the literature. We hope to extend these analyses to other neuronal datasets to validate this newfound connection between these differentially expressed genes.

Project: Investigation of TREM-2 Function in Alzheimer’s Disease

Mentors: Martine Therrien, Mike Dolan, Saša Jereb, Stevens lab at the Stanley Center for Psychiatric Disease