Cierra Weathers, a microbiology major at Texas A&M University, investigated the relationship between TREM-2 and Alzheimer’s disease.
Alzheimer’s disease (AD) is the 6th leading cause of death in the US, 3rd in people over the age of 65. AD is multifactorial, though genetic factors play a significant role in risk and development. One known gene associated with AD is TREM-2. TREM-2 is a gene that encodes for triggering receptors on myeloid cells (2), which are present in microglia. Changes in TREM-2 regulation can alter microglial activation, inflammation, phagocytosis, proliferation, metabolism, and survival. This dysregulation has been found to impact the brain’s immune response in Amyloid-beta pathology, one of two main mechanisms of AD progression. My time during BSRP 2020 has opened my eyes to science in such profound new ways. From learning effective research and communication through an all virtual format to making meaningful connections with my fellow cohort members despite never seeing each other in person, I will forever carry with me the lessons I’ve learned this summer. I’m immensely grateful to have grown alongside the 13 other brilliant young scientists of our cohort, and I’m eager to see where we go and the impacts we will have on our world.Due to the many impacts TREM-2 can have in the brain’s immune response, we aimed to identify genes associated with the upregulation and downregulation of TREM-2 to better understand the cellular and molecular underpinnings of TREM-2’s impact on AD. We utilized and repurposed the Cancer Cell Line Encyclopedia data for our studies, which is a database containing cell lines deeply characterized by genomic information. Regardless of cancerous implications, pathways can be conserved across cell lines and can further our knowledge in this area. Through differential expression analysis, we compared TREM-2 expressed and non-expressed cells and how this is linked with the subsequent regulation of other genes. Our results identified genes known to play important roles in AD in their own right. This could suggest TREM-2 is involved with the regulation of these genes identified which can be altered or lost with a loss of TREM-2 function. Connections between TREM-2 and the identified genes were validated in the STRING database as well. The genes identified by statistical analysis serve as promising targets of future work into further understanding the molecular mechanisms behind AD risk and development. Project: Elucidating Ties between TREM-2 and Alzheimer’s Disease
Project: Elucidating Ties between TREM-2 and Alzheimer’s Disease
Mentor: Rebecca Mandt, Dr. Dyann Wirth’s Lab at the Harvard T.H. Chan School of Public Health