Elucidating the Biological Roles Of tRNA Modification Enzymes

Pathogenic variants in tRNA modification enzymes are the cause of numerous diseases and disorders in the human population. However, the molecular basis of these pathologies are unknown due to major knowledge gaps that prevent our complete understanding of tRNA modification enzymes such as: How do modifications impact tRNA structure and function? What are the functions of vertebrate-specific tRNA modification enzymes? How do tRNA modification enzymes regulate cellular and developmental pathways? To resolve these knowledge gaps, our lab aims to elucidate the biological roles of tRNA modification enzymes. We will use an integrated approach combining biochemistry, molecular biology, and genetics with the development of new disease models and tools for detecting RNA modifications. We plan to decipher how modifications impact the global tRNA transcriptome to reveal conserved and novel roles for tRNA modification enzymes. Our studies will resolve the enigmatic functions of tRNA modifications and unravel the tissue- and cell-specific roles of tRNA modification enzymes linked to human disease. Importantly, elucidation of these mechanisms could reveal new modes of gene regulation that would inform strategies to understand and treat human pathologies linked to tRNA modification. Project Number: 1R35GM161348-01 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of General Medical Sciences (NIGMS) | Principal Investigator: Dragony Fu | Institution: UNIVERSITY OF ROCHESTER, ROCHESTER, NY | Award Amount: $578,733 | Activity Code: R35 | Study Section: Maximizing Investigators' Research Award A Study Section[MRAA] View on NIH RePORTER: https://reporter.nih.gov/project-details/11259298