|Awarded On||September 14, 2022|
|Title||Novel Modulators of Genomic Instability in Human Cells|
|Award Mechanism||High Impact/High Risk|
|Institution/Organization||The University of Texas at Austin|
|Principal Investigator/Program Director||Karen Vasquez|
|Cancer Sites||All Sites|
Cancer is initiated by genetic instability, a "hallmark" of cancer. The sites where cancer-causing instabilities occur are not random but are localized to genomic "hotspots" often comprised of sequences that can form alternative or "non-B" DNA structures (e.g., H-DNA). We found that these sequences are enriched at mutation hotspots in human cancer genomes in many cancer types and cause mutations in mammals, implicating them in cancer etiology. However, the mechanisms are still unclear, in part due to the lack of chemical probes to detect and/or regulate the formation of mutagenic non-B DNA in vivo and the limited platforms to identify and develop these tools. Thus, our g...