“More Than Just A, C, G, and U: RNA’s Secret Language and Human Health”
The Human RNome, the complete set of RNA molecules in human cells, emerges through complex processing steps. While RNA research has traditionally focused on the four canonical bases (A, C, G and U), growing evidence reveals extensive chemical modifications that shape RNA biology. Over 180 distinct ribonucleotides have been identified across organisms, including at least 50 in humans. Despite their critical roles in RNA structure and function, the principles governing the distribution and impact of these modifications remain largely undefined.
The Human RNome Project aims to sequence RNA with all its modifications, a challenge even more complex than sequencing the human genome. The International Human RNome Project Consortium is addressing key technical and conceptual gaps, developing essential research infrastructure, and advancing sequencing technologies to capture RNA modifications at single-nucleotide resolution. By deepening our understanding of RNA biology, this initiative will drive breakthroughs in therapeutics, agriculture, and non-biological applications such as data storage.
In this presentation, I will introduce the Human RNome Project, explore its significance, and highlight how RNA modifications influence gene expression and contribute to human diseases, with a particular focus on Alzheimer’s Disease.
About Dr. Cheung
Vivian G. Cheung, MD, is a distinguished RNA biologist and pediatric neurologist who serves as a professor in the Department of Molecular Biology, Cell Biology & Biochemistry, and Department of Pediatrics at Brown University.
Dr. Cheung’s research focuses on the genetic mechanisms of disease, particularly those driven by alterations in RNA processing and gene expression. Her group discovered that RNA sequences can differ from their corresponding DNA templates. She further demonstrated that these differences are explained by RNA modifications that occur soon after transcription, with nucleic acid structures like R-loops facilitating exposure of nascent RNA to modification enzymes. As a physician-scientist, she applies insights from her fundamental research to advance understanding of neurological disorders, including juvenile-onset ALS and Alzheimer’s disease.
Beyond research, Dr. Cheung has provided national leadership in science. She served as President of the American Society for Clinical Investigation. She was also the driving force behind the 2024 National Academies of Sciences, Engineering, and Medicine report, “Charting a Future for Sequencing RNA and its Modifications”. A dedicated advocate for diversity in the biomedical workforce, she has published op-eds in The Washington Post, The New England Journal of Medicine, and JAMA. Her mentorship has shaped the next generation of scientists, with her trainees earning prestigious honors such as the Rhodes Scholarship and the Harold Amos Medical Faculty Development Award.
Dr. Cheung earned her bachelor’s degree from UCLA and her medical degree from Tufts University School of Medicine, where she also completed a research fellowship at the J. David Gladstone Institutes. She returned to UCLA for her pediatrics residency and completed fellowship training at the University of Pennsylvania. She has held faculty and clinical appointments in pediatrics, neurology, and genetics at the University of Pennsylvania and The Children’s Hospital of Philadelphia as well as the University of Michigan.
Dr. Cheung’s contributions have been recognized with numerous honors, including the Scientific Achievement Award from the American Society of Human Genetics. She is an elected member of the American Society for Clinical Investigation, the Association of American Physicians, and the National Academy of Medicine.