The Hesselberth Lab

RNA Technology & Therapeutics · CU School of Medicine

Hesselberth Lab

A collaborative lab of RNA biologists, technology developers and data analysts, discovering and translating fundamental principles of RNA regulation — from how transfer RNA links the RNA and protein worlds, to RNA therapies built with clinicians at Children's Hospital Colorado.

Publications Meet the lab Software

RNA Bioscience Initiative · Biochemistry & Molecular Genetics · University of Colorado School of Medicine

Research

What we study

01RNA technology

We build sequencing methods and the software that makes sense of them: nanopore direct sequencing that reads modification and aminoacylation state on intact tRNAs, and single-cell and spatial approaches that measure biochemical activity alongside gene expression. Applied with collaborators, they track how antigen and viral RNA move through the lymph node.

Nanopore · Single-cell · Spatial · Open software

02RNA biology

Cells damage their own RNA, and repair it. We study how cleavage, end modification and processing are integrated into an RNA damage response, combining genetics, biochemistry and bioinformatics — work that has turned up new concepts in post-transcriptional regulation and, with collaborators, new determinants of nonsense-mediated decay.

RNA damage · Repair · tRNA · NMD

03RNA therapy

With clinicians at Children's Hospital Colorado we run a pipeline for antisense oligonucleotides that correct disease-causing splicing. The current focus is cryptic splicing — most recently an ASO that restores a ciliogenesis factor lost to a splicing mutation — alongside mRNA vaccine work with immunologists at CU Anschutz.

Antisense oligos · Cryptic splicing · Children's Hospital Colorado
Selected publications
(2025). Splice-switching antisense oligonucleotides correct cryptic exon inclusion and restore SDCCAG8 protein in Bardet-Biedl Syndrome.
DOI
(2025). Nanopore sequencing of intact aminoacylated tRNAs. Nat. Commun., 16(1), 7781.
DOI
(2025). Systematic analysis of nonsense variants uncovers peptide release rate as a novel modifier of nonsense-mediated mRNA decay. Cell Genom., 100882.
DOI
(2024). Comparative analysis of 43 distinct RNA modifications by nanopore tRNA sequencing. bioRxiv.
DOI
Latest news

Our NIGMS/NIH MIRA award was renewed.

We started a new shared resource to enable RNA-centric experiments: the RNA Informatics, Technologies, and Therapies Core (RITTC).

Emily DeCurtis was reappointed to the Molecular Biology NIGMS T32.

Welcome to Kai Tamburini, a high school intern, and to summer workers Aviana Funk and Jake Armstrong.

We were awarded VISTA and Gates Grubstake pilot awards to support our collaborative work with Suja Jagannathan, PhD and Scott Demarest, MD on therapeutic targeting of cryptic splicing.

Welcome to Adam Quach, an undergraduate from Metropolitan State University, and Jake Armstrong, co-founder of Andon Bio.

Emily DeCurtis was appointed to the Molecular Biology NIGMS T32.

Ira Fleming was awarded an NIH/NIAID F30 “Investigating the role of type 1 interferon signaling on mRNA stability within lymphatic endothelial cells”

We were awarded a Golfers Against Cancer Pilot Grant with Neel Mukherjee’s group.

We were awarded a Proof of Concept grant from the Colorado OEDIT Advanced Industries Accelerator program.

Illustration of the Hesselberth Lab at work