Mary Gates Research Scholar, Autumn 2024
Research Project: Investigating the Functional Relevance of the PSEN2 3′UTR Isoform Length
Project Description: Alzheimer’s disease (AD) is the most common form of dementia. Improper cleavage of amyloid precursor protein by a complex containing presenilin 1 or presenilin 2 (PSEN2) can result in pathological amyloid beta plaques. Recent work from the Valdmanis group found novel PSEN2 RNA isoform variants in sporadic onset AD, as well as two 3′ untranslated region (UTR) isoforms—a short and a long 3’UTR. The 3’UTR harbors essential regulatory elements such as miRNA binding sites and Alu elements that control transcript maturation, stability, and abundance. Using both in vitro and in vivo model systems, I aim to elucidate the functional significance of the PSEN2 3’UTR isoforms. Understanding how these 3′UTR variants impact amyloid beta accumulation and transcript regulation could uncover novel molecular mechanisms underlying sporadic AD. Given that AD affects over 6 million Americans and current therapies are limited, our project has the potential to inform new therapeutic strategies.
What have you learned throughout your research project?
Research has brought depth and context to my undergraduate coursework, especially in genetics, molecular biology, and neuroscience. Concepts that I have learned in class, such as gene regulation, transcript processing, and neurodegenerative disease pathways, have come to life through my work in the Valdmanis Lab. This experience has sharpened my critical thinking and problem-solving skills, while also strengthening my understanding of the scientific process. Since joining the lab in my sophomore year, I’ve grown as a communicator and collaborator, learning to navigate both the challenges and rewards of research. Above all, this experience has deepened my curiosity and affirmed my passion for biomedical science.
What piece of advice do you have for future applicants?
I would advise future applicants to build meaningful relationships with their mentors. As a student researcher, my mentors in the Valdmanis Lab are my strongest supporters and truly foster my passion for science. Learn from them, ask questions, and don’t be afraid to share your goals as they are there to help you get to where you want to go.