Hesselberth Lab

Department of Biochemistry and Molecular Genetics
RNA Bioscience Initiative
University of Colorado School of Medicine

We are a group of RNA biologists, technology developers, and data analysts on a mission to discover and leverage fundamental principles of RNA regulation.

The broad goals of our laboratory are to:

• Understand how RNA damage and repair are integrated with stress responses (funded by an NIGMS MIRA)
• Develop new molecular methods that enhance single-cell and spatial gene expression experiments (funded by an NIH Transformative R01)
• Develop and apply RNA therapeutics that modulate gene expression (funded by the RNA Bioscience Initiative)

A major effort in the lab focuses on the biology of RNA damage and repair using a combination of method development, bioinformatics, genetics, biochemistry, and cell biology. Over the past ten years we have developed new sequencing approaches to identify damaged RNAs and new model systems with which to understand the causes and consequences of RNA damage. Our studies have led to new concepts in post-transcriptional regulation that have broad implications for understanding the role of RNA damage in biology.

A second effort focuses on the development of novel technologies for analysis of additional phenotypes in single-cell and spatial gene expression approaches. Our recent advances include the measurement of enzyme activity and inhibition in single-cell assays, tracking of ligands and associated gene expression responses through animal tissue, and approaches for quantifying metabolite levels.

The newest effort in the lab is a collaboration with clinicians at Colorado Children’s Hospital to develop RNA therapies for treatment of pediatric neurological diseases. We are developing a pipeline using patient-derived cells to identify therapeutic antisense oligonucleotides that correct the negative impacts of mutations that alter pre-mRNA splicing.

Finally, we host the Informatics Fellows of the RNA Bioscience Initiative, who develop and apply bioinformatic approaches with investigators across our campus to enable widespread deployment of new RNA analysis technologies.