Non-coding RNA and neurological disorders,
RNA modifications, Mitochondrial metabolism,
Small molecular fluorescent imaging

Stress response and tRNA fragments in the regulation of glioma pathogenesis
Molecular mechanisms of protein misfolding and aggregation in neurodegenerative
diseases and the devolpment of therapeutic strategies targeting small RNAs

The Japan Society for Biomedical Gerontology
The Japanese Society of Neurology
The Japan Neuroscience Society
Japanese Society for Neurochemistry
The Japan Geriatrics Society
The Japanese Society of Internal Medicine
The Japanese Society for Dementia Research
The Japan Society for Medical Education
International Society for Neurochemistry (ISN)

Neurodegenerative diseases and brain tumors are intractable disorders that progress
through the accumulation of aberrant protein aggregates and dysregulation of cellular
stress responses; however, many aspects of their underlying molecular mechanisms
remain unclear. In recent years, tRNA-derived fragments (tRFs) and tRNA modifications
have emerged as a novel class of regulatory RNA molecules involved in stress responses and cellular homeostasis, yet their pathophysiological roles are largely unexplored. Our group has previously demonstrated that tRFs directly bind to tau protein, promoting its aggregation and cell-to-cell propagation, thereby identifying tRNA fragments as novel drivers of neurodegenerative disease progression. Furthermore, we have developed unique methodologies, including tRNA FISH and FISH-FRET, enabling the spatial visualization of RNA–protein interactions in situ. Using these approaches, we have also shown that chemical modification-based antisense oligonucleotides (2′-O-methyl ASOs) can modulate tRF function and effectively suppress disease-associated phenotypes.

Building upon these original findings and technological platforms, our research aims to
establish a unifying framework for disease mechanisms in neurodegenerative disorders
and gliomas based on a novel concept of “tRNA fragmentation regulation,” and to
translate these insights into RNA-targeted therapeutic strategies.

Identifying the molecular mechanisms underlying aberrant protein aggregation and propagation mediated by tRNA fragments
Using models of neurodegenerative diseases, we will investigate the direct interactions
between tRFs and pathological proteins such as tau at the molecular level, and define
how tRNA fragments drive protein aggregation and intercellular propagation as a novel
pathogenic mechanism.

Dissection of tRNA modification abnormalities and fragmentation control networks
in glioma
Focusing on tRNA-modifying enzymes such as METTL1 and TRMT10A, we will uncover
the molecular mechanisms by which aberrant tRNA modifications regulate tRF
biogenesis, and determine how disruption of this network contributes to tumor growth,
invasion, and therapeutic resistance.

Development of innovative RNA therapeutics and biomarkers targeting tRNA
fragments
We aim to establish disease-modifying strategies through the control of tRFs using
highly stable antisense oligonucleotides, and to develop non-invasive biomarkers based
on circulating tRFs for both neurodegenerative diseases and gliomas.

By positioning tRNA fragments as functional molecules that actively govern disease
processes, our research seeks to provide a new conceptual framework that extends
beyond conventional RNA biology. Furthermore, by integrating mechanistic insights with the development of nucleic acid therapeutics, our research is expected to contribute to the establishment of transformative treatment strategies for neurological diseases.