Assoc. Prof. Roca, Xavier
Associate Professor
Associate Chair (Research)
Phone: (65) 6592 7561
Email: [email protected]
Our research focuses on the study of the mechanisms of pre-messenger RNA splicing in human cells. The relevance of splicing is illustrated by these two facts: (1) on a fundamental level, alternative splicing is critical to explain the complexity of the human transcriptome and proteome, and contributes to many processes in cells and whole organisms; (2) on a biomedical level, a large fraction of genetic variants causing human hereditary disease and cancer affect splicing, and other syndromes are caused by alterations of splicing factors. The splicing and phenotypic consequences of many disease-causing mutations are not efficiently predicted, and the alternative splicing mechanisms and their interplay with other biological processes remain largely unknown. My lab tackles these challenges by a combination of computational, molecular and cell biology methods. Our two long-term goals are to improve the molecular diagnosis of splicing mutations causing genetic disease, and to elucidate the impact of alternative splicing in its biological context, with a focus on innate immune cells from the myeloid lineage, the regulation of antiviral genes, and the mechanisms of atypical cases. Last, we aim to apply this expertise to identify new therapeutic targets and develop RNA-based therapies.
Research Areas
Splicing mechanisms, alternative splicing, human myeloid cells, antiviral genes, genetic variants
PhD Student
Research Fellow
Project Officer
Research Fellow
PhD Student
Research Fellow
Research Fellow
- Tian, C., Zhang, Y., Tong, Y., Kock, K.H., Sim, D.Y., Liu, F., Dong, J., Jing, Z., Wang, W., Gao, J., Tan, L.M., Han, K.Y., Tomofuji, Y., Nakano, M., Buyamin, E.V., Sonthalia, R., Ando, Y., Hatano, H., Asian Immune Diversity Atlas Network, Loh, M., Chambers, J., Hon, C.C., Choi, M., Park, J.E., Ishigaki, K., Okamura, T., Fujio, K., Okada, Y., Park, W.Y., Shin, J.W., Roca, X., Prabhakar, S., and Liu, B. “Single-cell RNA‑seq links cell-type‑specific regulation of splicing with complex diseases.” Nature Genetics 56 (2024): 2739–2752. https://doi.org/10.1038/s41588-024-02019-8
- Tan, C.W., Sim, D.Y., Zhen, Y., Tian, H., Koh, J., and Roca, X. “PRPF40A induces inclusion of exons in GC-rich regions important for human myeloid cell differentiation.” Nucleic Acids Research 52 (2024): 8800–8814. https://doi.org/10.1093/nar/gkae557
- Xu, S., Lai, S.K., Sim, D.Y., Ang, W.S.L., Li, H.Y., and Roca, X. “SRRM2 organizes splicing condensates to regulate alternative splicing.” Nucleic Acids Research 50 (2022): 8599–8614. https://doi.org/10.1093/nar/gkac669
- Ly, P.T., Xu, S., Wirawan, M., Luo, D., and Roca, X. “ZAP isoforms regulate unfolded protein response and epithelial‑mesenchymal transition.” Proceedings of the National Academy of Sciences USA 119 (2022): e2121453119. https://doi.org/10.1073/pnas.2121453119
- Goh, Y.T., Koh, C.W.Q., Sim, D.Y., Roca, X., and Goh, W.S.S. “METTL4 catalyzes m^6Am methylation in U2 snRNA to regulate pre-mRNA splicing.” Nucleic Acids Research 48 (2020): 9250–9261. https://doi.org/10.1093/nar/gkaa684