01/28/2026

Nupur Bhatter joined the lab as a postdoctoral fellow.

01/05/2026

Eric Pham and Regan Miller joined the lab as undergraduate trainees. Pooja Kharel joined the lab as ISRD trainee.

07/17/2025

New paper out in Science (Collaborative work with Saumay Das’s Lab at HMS).

Transfer RNA–derived small RNAs (tDRs) perform a range of cellular functions. Here, we showed that tRNA-Asp-GTC-3′tDR, a hypoxia-induced tDR derived from the 3′ end of tRNA-Asp-GTC, activated autophagic flux in kidney cells and its silencing blocked autophagic flux. Functional gain-/loss-of-function studies in murine kidney disease models demonstrated a substantial renoprotective function of tRNA-Asp-GTC-3′tDR. Mechanistically, tRNA-Asp-GTC-3′tDR assembled stable G-quadruplex structures and sequestered pseudouridine synthase 7 (PUS7), preventing catalytic pseudouridylation of histone mRNAs. The resulting pseudouridylation deficiency directed histone mRNAs to the autophagosome-lysosome pathway, triggering RNA autophagy. This tDR-induced RNA autophagy pathway was activated during murine and human kidney diseases, suggesting clinical relevance. Thus, tRNA-Asp-GTC-3′tDR plays a role in regulating RNA autophagy, which helps to maintain homeostasis in kidney cells and protects against kidney injury.

Read the A hypoxia-responsive tRNA-derived small RNA confers renal protection through RNA autophagy online.

07/08/2025

New paper out in Nucleic Acids Research.

Guanine-rich nucleic acid sequences can exert sequence- and/or structure-specific activities to influence biological and pathobiological cellular processes. As such, it has been reported that different G-rich oligonucleotides (both DNA and RNA) can have cytotoxic as well as cytoprotective effects on the cells. However, the mechanisms of such a biological outcome are unclear. Here, we report that G-rich DNA oligonucleotides (ODNs) that can form four-stranded secondary structures called G-quadruplexes (G4s) have a topology-dependent biological outcome. Using different biochemical, biophysical, and cellular approaches, we demonstrate that only the parallel topology G4-forming ODNs can repress eukaryotic messenger RNA (mRNA) translation by directly interacting with eukaryotic translation initiation protein 1 (EIF4G1), while the anti-parallel topology G4s do not have inhibitory effect on mRNA translation. These results directly connect the G4 topological differences within ODNs to differential functional impacts in mRNA translation in trans. Our study provides the foundation for the rational design of G-rich oligonucleotides for a desired therapeutic outcome.

Read the G-quadruplex topologies determine the functional outcome of guanine-rich bioactive oligonucleotides online.

07/01/2025

Kharel Lab: Laboratory of RNA Biology and Therapeutics is open!

06/05/2025

Prakash gave a talk on “G-quadruplex topologies determine the functional outcome of guanine-rich bioactive oligonucleotides” at the 9th International Conference on G‑quadruplexes (9th G4thering). 

04/28/2025

Prakash joied KUMC as an Assistant Professor of Biochemistry and Molecular Biology.