Kalli Kappel, PhD

RNA-binding proteins (RBPs) bind mRNA molecules and control nearly all aspects of their fate, including processing, localization, translation, and stability. Dysregulation of RBPs is increasingly recognized as a major driver of cancer, where altered RBP expression, mutation, or localization can reshape oncogenic gene expression programs, influence proliferation, metastasis, and therapeutic resistance, and fundamentally alter cell state. Dr. Kappel's lab develops high-throughput experimental and computational approaches to decode the sequence rules governing RBP localization and function, condensate assembly, and mRNA fate at a scale and resolution not previously possible. By combining optical pooled screening, machine learning, and integrative structural modeling of mRNP complexes, they aim to define how cancer-associated mutations in RBPs and noncoding RNA sequences rewire post-transcriptional gene regulation, and to build predictive frameworks that connect sequence variation to regulatory outcomes. This work will reveal new mechanisms of post-transcriptional dysregulation in cancer and identify the structural and functional vulnerabilities in RNA regulatory complexes that could be exploited therapeutically.

Kappel K+, Strebinger D, Edmonds KHK, VO SCDT, Vockley CM, Biswas T, Farhi SL, Macrae R, Zhang F, Regev A+. Characterizing protein sequence determinants of nuclear condensates by high-throughput pooled imaging with CondenSeq. Nature Methods. (2025). doi: https://doi.org/10.1038/s41592-025-02726-y