Dain Ruiz, a junior biology major and music and global cinema double minor at the University of North Carolina at Chapel Hill, impact of post-translational modifications on Down syndrome.
Down syndrome is a neurodevelopmental disorder caused by trisomy 21 and characterized by a spectrum of phenotypes, including intellectual disability as well as elevated rates of autism, Alzheimer’s disease, and certain types of leukemias. The Broad Summer Research Program provides an excellent opportunity to connect with brilliant scientists and students, all while conducting meaningful research at the same time. My experience in BSRP this summer has strengthened my career aspirations and helped me grow as a leader, scientist, and person.Previous work has shown genome-wide changes in the transcriptomes of brain tissue from Down syndrome patients. We hypothesize that changes in the epigenome contribute to the dysregulation of gene expression in Down syndrome. We therefore aim to identify and characterize specific epigenetic alterations due to trisomy 21 using human iPSCs and in vitro derived brain cell types to understand molecular mechanisms relevant for human development. We recently identified alterations in the abundance of several histone post-translational modifications (PTMs) using isogenic human iPSC-derived neurons with and without trisomy 21. Our specific objectives for this project are therefore to: 1) Define genome-wide binding patterns of relevant histone PTMs in trisomy 21 versus euploid controls; and 2) Assess the impact of histone PTM normalization on downstream molecular and cellular phenotypes. A deeper understanding of epigenetic rewiring may ultimately lead to novel therapeutic opportunities for Down syndrome patients.
Project: Probing the impact of Down Syndrome on the histone code using human cellular models
Mentors: Dr. Anna Nathanson, Darina Trendafilova, and Dr. Lindy Barrett, Harvard University, Department of Stem Cell and Regenerative Biology, Stanley Center for Psychiatric Research at Broad Institute