Sofia Lombana Rengifo
Sofia Lombana Rengifo, a senior biotechnology and biopsychology major at Tufts University, identified the differentially expressed genes that have been associated with Alzheimer’s disease in a TREM-2 background.
Alzheimer’s disease (AD) is a neurodegenerative disorder that is characterized by a dramatic decline in the patients’ thinking, behavioral, and cognitive skills. A significant hallmark of AD pathology is the accumulation of amyloid-beta (Aβ) plaques in the brain. Failure to clear Aβ plaques compromises brain homeostasis and has been linked to genetic variations of the triggering receptor expressed on myeloid cells 2, or TREM-2. TREM-2 is expressed in the surface of microglia, the macrophages of the brain, and it is crucial for the regulation of the brain’s immune response. TREM-2 deficiency is associated with the aggregation of Aβ plaque and exacerbates the progression of AD.
The BSRP allowed me to be part of a collaborative, supportive, and diverse environment that transforms the most complex scientific conundrums into trailblazing discoveries. The cross-disciplinary culture at the Broad equipped me to solve problems by integrating different perspectives and areas of knowledge. Being surrounded by my brilliant mentors and cohort inspired me to explore computational biology and was pivotal to my growth as a scientist. I am grateful for the opportunity to integrate my identities and passions to contribute to the scientific community and look forward to finding more answers at the Broad in the future.
In the present computational study, we conducted differential expression analysis using the Cancer Cell Line Encyclopedia (CCLE) to identify the differentially expressed genes in a TREM-2 wild type background. This database contains valuable gene expression information for a large number of immortalized cancer cell lines. The CCLE was a useful tool since the essential mechanisms involved in the development of AD pathology are conserved across different cell lines.
Our results indicated that AZU1, PRTN3, TYROBP, MPO, and ELANE are the upregulated genes associated with AD when TREM-2 wild type is expressed. We validated these results through the STRING database, which provided us with further evidence of a true biological interaction between the aforementioned genes. This study shows the wide applicability of the CCLE to study the genes implicated in AD and draws attention to the investigation of how these molecular interactions might contribute to neurodegeneration.
Project: Differential Expression Analysis of TREM-2 in Alzheimer’s Disease
Mentor: Juliana Coraor, Dr. Anna Greka’s Lab