Rachel Lim joined the Prasov Lab as a pre-med student interested in ophthalmology and surgery. She sought a deeper understanding of the eye, especially since few undergraduate courses explore it in detail. Over the past two years as a senior research assistant, that curiosity has grown into an honors thesis project focused on the genetics of nanophthalmos, a rare condition characterized by small but structurally normal eyes.
Her current project, “Pathogenic Loss of Function Variant in MYRF ICA Domain Results in Isolated Nanophthalmos”, focuses on understanding how a newly identified MYRF variant may contribute to isolated nanophthalmos. While the condition is known to have a genetic basis, only about 20% of cases can currently be explained by identified genes. In the Prasov Lab, an R695C variant in MYRF was found in a patient with isolated nanophthalmos, and Rachel’s work aims to understand what that specific change actually does. She studies whether the variant affects how MYRF functions in the retinal pigment epithelium (RPE), a cell layer that plays an important role in maintaining retinal health.
To explore this further, Rachel combined patient sequencing data with structural modeling and lab-based experiments. Using tools such as Ensembl VEP and AlphaFold3, she examined how the R695C variant might affect the shape and stability of the MYRF protein. The modeling suggested that this substitution disrupts a hydrogen bond within the ICA domain. Since the ICA domain cleaves MYRF to activate it as a transcription factor, any disruption in this process could prevent the protein from entering the nucleus and carrying out its role in regulating gene expression.
She then moved into cell-based experiments to test this prediction in ARPE-19 cells using engineered DNA constructs. Imaging revealed that the R695C variant remains in the endoplasmic reticulum rather than entering the nucleus, as observed in known cleavage-deficient controls. Getting to that point was not straightforward. She redesigned primers, adjusted experimental conditions, and worked through multiple rounds of troubleshooting when results did not initially align with expectations. Rather than viewing setbacks as failures, she learned to treat them as useful information. As she describes it, “a no is still a yes,” since each unexpected outcome helped guide the next step of the project.
Beyond the results themselves, this project has played an important role in Rachel’s growth as a researcher. With guidance from her mentor, Dr. Gabrielle Rozumek, and support from Principal Investigator Dr. Lev Prasov, she learned how to work through setbacks and rethink experiments when things did not go as planned. Over time, she became more comfortable taking ownership of the project and making decisions about next steps. She credits her mentors for being patient and invested in her development, helping her learn to approach challenges thoughtfully and adjust her methods rather than get discouraged.
Working on a rare disease has also given the project personal meaning. Each experiment adds another piece of understanding to a condition that has many questions still unanswered. Seeing how patient data can be translated into molecular mechanisms has strengthened her interest in pursuing medicine, potentially in pediatric surgery or pediatric ophthalmology. As she prepares for the MCAT and plans for a gap year, Rachel hopes to continue working on service-oriented initiatives, including projects supporting children in underserved communities.
Research has given Rachel a way to explore her interest in ophthalmology in a hands-on manner. Over time, she’s learned how to handle setbacks, rethink experiments, and stay patient when results don’t come easily. With guidance from her mentor and support from her lab team, she’s been able to contribute to understanding how MYRF variants relate to nanophthalmos. At the same time, the experience has helped her grow more confident in her abilities and clearer about the kind of physician and researcher she hopes to become.
Research Award: Rachel Lim
By: Zahraa Alfatlawi
