Our lab is rigorously investigating the roles of the RNA polymerase II-associated multiprotein complex, Integrator, in gene expression regulation, epigenetics, and signaling pathways, and how they are manipulated in cancer. We are also exploring the mechanisms of a class of long noncoding RNAs that arise from enhancer elements and behave similar to transcriptional enhancers, in the context of relevant models of development and disease. In our lab, we combine state-of-the-art technologies in genomics, proteomics and high-resolution imaging to probe into these fundamental biological questions.
Through out the years, the Shiekhattar laboratory has made a number of seminal discoveries identifying and characterizing important mediators of epigenetic regulation and noncoding RNA processing that contribute to cancer development.
Integrator functions in development and disease
Integrator is a 14-subunit protein complex functioning in both RNA transcription regulation and processing. Integrator also relay stimulates from signaling pathways to gene expression. Mutations in Integrator subunits have been indicated in both immunodeficiency and severe neurodevelopmental delay.
Enhancer RNA functions
Intergenic and intragenic enhancers express noncoding RNA, called enhancer RNA (eRNA). eRNAs play a role in gene regulatory networks by controlling promoter and enhancer interactions and topology of higher-order chromatin structure.
Small molecule cancer therapies
Protein phosphorylation plays a major role in cellular signaling. Disturbance in the balance between the activities of protein kinases and phosphatases could result in abnormal cell growth, which could lead to cancer. Protein phosphatases have been implicated in oncogenesis and tumor progression and therefore are potential drug targets for cancer chemotherapy.