Angelina
Angelina
Mystic Valley Regional Charter School
Malden, MA
Mentor:
Alinés Lebrón-Torres
Cancer Program
Angelina joined BSSP to work at the intersection of cancer biology, genetic engineering, and precision medicine. Her project investigated whether abnormal RNA molecules found specifically in leukemia cells could be turned into molecular switches, allowing the selective expression of a therapeutic protein payload in their presence.
Angelina and Sophia focused on targeting leukemia fusion RNAs produced by structural changes in cancer genomes. The team specifically targeted 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.The ultimate vision is a programmable system in which a cancer-defining RNA triggers therapeutic protein production while cells lacking that RNA leave the sensor off.
Over the summer, Angelina developed experience with the experimental pipeline needed to evaluate these sensors. The project incorporated molecular cloning, transfection, live-cell imaging, PCR, gel electrophoresis, sequencing, fluorescent antibody staining, and flow cytometry. The team also tested different sensor architectures, including linear sensors that directly span a fusion breakpoint and gap sensors designed to recognize separated regions of the two fusion partners.
Their experiments provided strong proof-of-concept evidence.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. 17 of 20 targeting sensors showed increased activation of payload when the target RNA was present, and several sensors demonstrated particularly strong target-dependent responses, with up to 8.8-fold increase between the no-target and target conditions.
Through this work, Angelina learned how an engineered molecular idea moves from sensor design to controlled cell experiments and quantitative validation, and why selectivity is central to developing precision cancer therapeutics.
Angelina's work contributes to a larger effort to make cancer therapeutics increasingly programmable and selective. The next steps include testing cytotoxic protein payloads and determining whether the RNA-sensing technology can ultimately deliver selective expression of a therapeutic protein based on their unique molecular features of cancer cells.
The experience also changed how Angelina saw herself in science. She called BSSP “the happiest six weeks of my life” and said that immersing herself in an unfamiliar research world alongside her lab partner showed her that conducting and presenting research did not have to feel boring or intimidating. By the end of the summer, she felt confident that she belonged in scientific spaces and could connect with others through science.
