Meet Our Researchers
Sarah Pierce
“Many gene-editing approaches focus on a specific disease. My aim is to develop gene therapies that can be applied more broadly.”
Though gene therapy has revolutionized treatment for genetic diseases, most approaches remain mutation-specific, requiring tailored interventions for each mutation. But what if we could develop gene therapies that work across different mutations?
Genetic mutations known as nonsense mutations produce shortened, truncated proteins that are often nonfunctional. But in some diseases, nonsense mutations trigger regulatory mechanisms that restore normal function. This kind of regulatory mechanism is called transcriptional adaptation. What’s unknown is the extent to which transcriptional adaptation occurs across different genes and diseases. Leveraging prime editing—a precise DNA-editing tool developed by the Liu Lab—Sarah will introduce nonsense mutations into genes. As a first step, she will use CRISPR screens to map all genes capable of undergoing transcriptional adaptation. Next, she’ll investigate the small RNAs that mediate transcriptional adaptation, attempting to discover if they can be harnessed and enhanced for therapeutic benefit. If so, Sarah’s project could lead to a new class of RNA-based therapies, expanding the therapeutic landscape for genetic diseases beyond mutation-specific approaches and paving the way for broadly applicable gene therapies.