Federal Project Grant Award Summary

The University of Pittsburgh received a $673,522 Project Grant from the National Cancer Institute under the Cancer Cause and Prevention Research program (CFDA 93.393) for the period July 1, 2026, through June 30, 2031. Under the direction of Principal Investigator Orlando Scharer, this award funds comprehensive research into the dynamic processing of DNA lesions by human nucleotide excision repair (NER), a critical cellular pathway that protects genomes from damage caused by solar UV irradiation and environmental toxins. The research addresses substantial knowledge gaps in how NER recognizes, verifies, and processes DNA lesions, with particular focus on understanding the mechanisms that govern the transition from damage recognition to dual incision—findings with significant implications for cancer therapy resistance and precision oncology applications.

The project delivers research products and analysis through multiple integrated approaches, including the assembly and biochemical characterization of NER complexes, cryo-electron microscopy studies of NER machinery at various reaction stages, and structural determination of damage verification complexes as they process cisplatin and acetyl amino fluorene lesions. These research outputs will contribute to the Cancer Cause and Prevention Research program's objective of identifying cancer risks and developing cancer prevention mechanisms by elucidating the molecular mechanisms underlying a pathway critical to both cancer susceptibility and chemotherapy resistance.