Yaohua Yang, PhD
Yaohua Yang, PhD, an assistant professor in the Department of Genome Sciences and a member of the University of Virginia Comprehensive Cancer Center, has received a five-year, nearly $3.5 million R37 MERIT award from the National Cancer Institute (NCI). The award supports a project titled “Identification of N6-methyladenosine (m6A) marks and genes influencing lung cancer risk.”
The NCI R37 Method to Extend Research in Time (MERIT) award is not something investigators can apply for directly. NCI program staff identify R01 applications from early-stage investigators that score within the institute’s payline and nominate them to the National Cancer Advisory Board. Awardees may then receive an extension of up to two additional years with new funding, based on an expedited NCI review, for as much as seven years of support for a single project.
Lung cancer remains the leading cause of cancer death in the United States, and much of the inherited risk for the disease is still unexplained. Yang’s project centers on m6A, the most common chemical modification of messenger RNA, which helps determine how RNA molecules are spliced, exported from the nucleus, stabilized, and translated into protein. Disruption of the cellular machinery that adds and removes m6A marks has been linked to lung tumor development, but how individual m6A marks relate to a person’s risk of developing lung cancer has remained largely uncharted.
The project combines genetic epidemiology, multi-omics profiling, and laboratory experiments. Yang’s team will first build genetic models that predict m6A levels in lung tissue from healthy donors, then apply those models to existing genome-wide association studies to test m6A marks for association with lung cancer risk. The approach makes it possible to study m6A at population scale without directly profiling the modification in tens of thousands of people. The team will then compare how m6A shapes RNA behavior in tumor tissue versus normal lung, and use CRISPR editing to test whether the most promising marks and genes actually change how lung cells grow, migrate, and form colonies.
Analyses will be carried out in both European-ancestry and African-ancestry populations and stratified by smoking status and tumor subtype, addressing a persistent gap in genomic studies of lung cancer. The findings are intended to support m6A-based risk prediction and to identify RNA modifications that could be targeted for prevention or treatment.
“Lung cancer kills more Americans than any other cancer, yet we still cannot explain much of why one person develops it and another does not,” Yang said. “By treating RNA modifications as a measurable layer of biology sitting between our genes and our cells, we hope to uncover risk mechanisms that DNA alone has not revealed, and to point toward new ways to predict and prevent this disease.”
Yang is joined on the project by Co-Investigator Kexin Xu, PhD, a professor in the UVA Department of Genome Sciences. The award also supports collaborations with Jianjun Chen, PhD, at City of Hope; Xin He, PhD, at the University of Chicago; and Qiuyin Cai, MD, PhD, and Bradley Richmond, MD, PhD, both at Vanderbilt University Medical Center.
Dr. Yang also serves as population science co-lead of the Gastroenterology Translational Research Team and as scientific leader of the Microbiome and Cancer Epidemiology Research Program, both at the UVA Comprehensive Cancer Center.
The research is supported by NCI grant R37CA309508. Details of this award are available at NIH REPORTER: https://reporter.nih.gov/search/AebO-4gSYkOKMBqVDJtjZg/project-details/11449219.
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