Federal Grant Award Summary

The University of Pittsburgh received a $434,212 Project Grant from the National Institute of General Medical Sciences (NIGMS) under the Biomedical Research and Research Training program (CFDA 93.859), effective March 1, 2026 through December 31, 2030. This award supports fundamental research investigating the mechanistic basis of DNA replication initiation in human cells. The project employs integrated cell biology, genetic, and proteomic approaches to identify novel origin firing factors, elucidate the sequential recruitment of proteins to replication origins, and determine how chromosomal context—including chromatin marks, transcription start sites, and other genomic features—influences origin activation mechanisms. Using split-TurboID proximity labeling combined with analysis of replication complex-associated proteins, the research aims to distinguish which origin firing factors are universally required for replication initiation versus those specific to particular replication origin subsets.

This research directly advances NIGMS's mission to support basic biomedical research that enhances understanding of biological processes fundamental to disease prevention and treatment. The investigation addresses a critical gap in mammalian replication biology, as DNA replication initiation has not been fully reconstructed in vitro and multiple aspects of origin regulation in human cells remain incompletely characterized. By clarifying how cells license and activate diverse replication origins, the project contributes to understanding genome stability mechanisms and cellular responses to replication stress, with potential implications for cancer biology and cellular disease processes.