Lab News
06/26/2026
Prakash attended the 33rd Annual International Research Conference on FSHD in Chicago, and delivered a spotlight presentation on ‘Context‑dependent regulatory functions of DUX4 G-quadruplexes in FSHD’.
06/22/2026
Ruptanu Banerjee joined the lab as a postdoctoral fellow.
05/29/1016
Prakash attended the 31st Annual RNA Society Conference in Montreal, where he presented a poster titled ‘Single-Nucleotide Variations Determine the Mechanism of Translation Repression by G-Quadruplex–Assembling tRNA-Derived RNAs.’
05/17/2026
Our new preprint is out on bioRxiv (Collaborative work with Anna Krichevsky’s Lab at BWH/HMS), tRNA-derived fragments elevated in Alzheimer’s disease facilitate Tau aggregation
Abstract: Tauopathies, including Alzheimer's disease (AD), are driven by pathological Tau aggregation, a process that requires co-factors. Small RNAs (sRNA) have been proposed as such co-factors, yet little is known about endogenous transcripts that promote Tau pathology. We identify stress-induced tRNA-derived RNAs or fragments (tDRs/tRFs) as the most dysregulated sRNA class in human AD brains, PS19 mice overexpressing mutant human Tau, and human neuronal tauopathy models. Notably, the highly accumulating 5′Glu-CTC and 5′GlyGCC tRFs induce Tau S396 phosphorylation, oligomerization, and impact neurite growth. Moreover, 5′Glu-CTC is enriched in pathological Tau precipitates and co-localizes with oligomeric Tau in PS19 mouse brains. Inhibiting 5′Glu-CTC mitigates Tau pathology. Furthermore, these tRFs are highly secreted by stressed neurons and can be taken up by recipient cells, implicating them in the propagation of pathology. Our findings establish 5′Glu-CTC as a key regulator of Tau aggregation and suggest its inhibition as a promising therapeutic strategy for tauopathies.
05/08/2026
Prakash was invited by the American Association of Pharmaceutical Scientists (AAPS) UMKC Student Chapter to speak as part of the AAPS Departmental Seminar Series, where he presented a seminar titled ‘Small but Mighty: A Tale of the Non-Canonical Functions of tRNA-Derived RNAs’.
04/28/2026
Nupur presented a poster titled ‘Repurposing tRNA isodecoders into tDRs with variable functions’ in the BMB departmental retreat.
04/24/2026
Eric presented a poster titled ‘Effect of different cations on the assembly of tetramolecular G‑quadruplexes formed by tRNA‑derived RNAs’ at the Rockhurst University Research Forum.
04/16/2026
Prakash presented an invited seminar, ‘Guanine quadruplexes in RNA biology and therapeutics,’ hosted by the Division of Biological & Biomedical Systems at the University of Missouri–Kansas City.
04/15/2026
Prakash delivered a keynote address titled ‘Beyond the double helix: G‑quadruplexes in health and disease’ at the Science and Mathematics Undergraduate Research Forum at the University of Saint Mary, Leavenworth, KS.
03/23/2026
Fabian Lopez joined the lab as a research assistant.
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.