ÃÛÌÒAPP

We humans have evolved largely by acquiring diversity in alternative RNA metabolisms, including alternative means of splicing and polyadenylation, rather than acquiring new coding genes. Alternative pre-mRNA splicing regulates the majority of mammalian genes, with more than 95% of multi-exon genes undergoing regulated splicing. This process is fundamental to a wide range of biological functions, including cell proliferation, lineage specification, differentiation, tissue morphogenesis, signaling, and immune responses. By diversifying the proteome, alternative splicing enables the generation of distinct cellular identities and functional states from an otherwise homogeneous genome.

The Nazim Lab investigates how post-transcriptional gene regulation is orchestrated at both the RNA and chromatin levels. We are particularly interested in understanding how alternative RNA splicing influences transcriptional and epigenetic programs in embryonic stem cell maintenance, differentiation, and tissue development. A major focus of the lab is defining how different splice variants of chromatin regulators function during cellular differentiation into distinct lineages, and how errors in RNA splicing contribute to human diseases, including various neurodevelopmental disorders and cancer. Utilizing cell culture systems, genetically engineered mouse models, and modern genomic approaches, we investigate how splicing-driven changes in gene regulation support normal development and how these processes go awry in disease. Our goal is to uncover fundamental principles that connect RNA biology, chromatin regulation, and gene expression in human health and disease.