Integrator Complex In Development

 A central regulator of gene expression that has emerged in the last decade is the Integrator complex, which is comprised of 15 distinct subunits that form various modular units. Integrator contributes to transcriptome homeostasis via post-transcriptional processing of small nuclear RNA involved in splicing, as well as transcriptional pause release to regulate the production of protein-encoding genes. Mutation to the Integrator has emerged as a causal link to neurodevelopmental defects in humans. Our lab has been characterizing genetic regulators of the Integrator and is interested in using C. elegans to model how this protein complex contributes to developmental and aging physiology. 

Recent work in this area:

· Waddell and Wu, PloS Genetics (2024)

· Waddell and Wu, G3 (2025)

· Waddell et al., Biology Open (2025)

Modifications to RNA molecules after transcription are an important step in producing a stable and mature molecule required to produce cellular building blocks. Examples of such modification include RNA splicing and 5’ and 3’ transcript processing. Our lab has shown that exposure to certain environmental chemicals can alter RNA splicing dynamics, which, when defective, is linked to several human pathologies (e.g. neurological disorders, aging, malignancies). Currently, we are particularly interested in characterizing environmental and genetic factors that influence 3’ transcript cleavage, which are found in non-coding snRNA molecules and replication-dependent histones. 

Recent work in this area:

• Chomyshen et al., Genetics (2022)
• Huynh and Wu, G3 (2023)

 The use of animal models for screening environmental chemicals for toxicity is an important step towards determining potential hazards to humans. Taking advantage of the C. elegans transgenic toolbox, our lab has been testing for environmental chemicals that induce cellular stress, including onset of oxidative stress and RNA splicing disruption. Once chemicals of interest are identified, we apply genetic screening approaches to understanding cellular pathways that regulate these stress responses.

Recent work in this area:

• Huynh and Wu, Free Radic Biol Med(2022)
• Tabarraei et al., Aging Cell (2023)
• Kardal et al., J Pharmacol Toxicol Methods (2025)