Sophia

Sophia
Quaboag Regional High School
Quaboag, MA

Mentor: 
Alinés Lebrón-Torres
Cancer Program

 

Sophia spent her summer exploring an ambitious question in precision cancer medicine: could a cancer cell's own abnormal RNA be used as a signal to selectively turn on a therapeutic protein? Working on a project focused on leukemia, Sophia helped test engineered RNA sensors designed to recognize fusion RNAs, abnormal RNA molecules created when pieces of two genes become joined together through cancer-associated chromosomal rearrangements. 

The team targeted a clinically relevant leukemia fusion RNA ETV6::RUNX1 using reprogrammable ADAR-mediated RNA sensors, or RADARS. When a sensor encounters its matching fusion RNA, it forms a double-stranded RNA structure that recruits the cell's naturally occurring ADAR enzyme. ADAR edits a strategically placed premature stop codon in the sensor, allowing the downstream translation of a linked protein payload. In this way, the cancer-specific RNA acts almost like a molecular trigger: when the correct target is present, the sensor switches "on." 

Working alongside her partner, Angelina, Sophia gained exposure to a wide range of molecular and cellular techniques, including sensor design, Golden Gate cloning, transient transfection, gel electrophoresis, live-cell imaging, RT-PCR, Sanger sequencing, antibody staining, and flow cytometry. The team first confirmed the fusion RNA breakpoint sequence in a leukemia cell line naturally expressing ETV6::RUNX1. Then, they tested ETV6::RUNX1 targeting sensors using hNGFR as a reporter payload in cells with and without target RNA present. Their results were especially encouraging: 17 of 20 targeting sensors demonstrated target-dependent activation, with the strongest sensors producing substantially greater reporter expression when the fusion RNA was present (up to 8.8-fold increase between the no-target and target conditions). 

Through the project, Sophia learned how sensor design, molecular cloning, cell-based testing, sequencing, imaging, and flow cytometry work together to evaluate whether an engineered RNA system is both functional and selective. 

Sophia's project illustrates how fundamental RNA biology and nucleic-acid technologies can be leveraged into impactful potential precision-medicine strategies. Future work will test these sensors with cytotoxic protein payloads, optimize ADAR-dependent editing, and establish design rules that could eventually make the platform adaptable to different cancer-specific RNA targets. 

For Sophia, taking on difficult science became part of learning to move beyond her comfort zone. She said BSSP allowed her to gain “endless knowledge” through cutting-edge research that could one day improve lives, and that even when the science feels hard, “it’s so worth it to learn and help others.”