Research
1. Mechanisms of mRNA polyadenylation
mRNA polyadenylation is a crucial step in eukaryotic gene expression, influencing mRNA stability, translatability, and cytoplasmic translocation. This process also impacts pre-mRNA splicing and transcription termination. Recent research has linked mRNA polyadenylation to various cellular processes, including responses to environmental stimuli, pathogen invasion, and cancer development.
Our lab aims to uncover the molecular mechanisms of mRNA polyadenylation at genetic, transcriptomic, and genomic levels, examining both tissue-specific and single-cell contexts. We use functional genomic tools to study these mechanisms in model plants such as Arabidopsis and rice, focusing on the biochemical, genetic, and molecular functions of polyadenylation factors and their roles in plant gene expression during development and stress responses.
Leveraging advanced RNA-sequencing technologies, we conduct large-scale analyses of alternative polyadenylation (APA) to map the comprehensive landscape of APA across single cells and entire organisms. With over 70% of genes utilizing APA for expression regulation, the role of APA in cellular and organismal functions is just beginning to be understood. Our multi-omics approach reveals that APA is linked to various cellular processes, including circadian regulation, epigenetic control, and quantitative traits, highlighting its role as a central hub for fine-tuning gene expression at the transcriptome level.
2. Gene expression in neuronal cell communication
Our research collaboration extends to gene expression regulation in human induced pluripotent stem cells (iPSCs), particularly in neuronal disease models like Alzheimer’s disease (AD). AD and related dementias present a global challenge, characterized by extensive neuronal loss, yet the mechanisms behind this loss remain unclear.
Microglia, the central nervous system’s resident immune cells, are suspected to play a role in AD pathogenesis. We explore how extracellular vesicles (EVs) — lipid bilayer membrane vesicles 30 to 200 nm in diameter, generated by the endosomal system — influence cell-to-cell communication. EVs contain proteins, mRNA, and miRNA that can modulate gene expression in recipient cells. Notably, microglia-derived microvesicles have been shown to regulate neuronal excitability, representing a promising area of research in neurodegenerative diseases.
We employ multi-omics tools to analyze the components of microglia-derived EVs in AD-like models derived from patient and control samples. Identifying these potential markers and their roles in regulating gene expression, especially concerning neuronal degeneration, could provide new insights into neuronal gene expression regulation and identify potential targets for future drug development.
3. Gene expression regulation in development and responses
In collaboration with various research groups, we study gene function and expression related to plant development and responses to environmental stimuli.
Mangroves, for example, are woody plants that thrive in extreme coastal conditions. Their unique adaptations, such as viviparous seed reproduction, pneumatophores for submergence and hypoxia, and various salinity responses, are of significant interest due to their potential applications in crop breeding programs. We investigate these adaptations through gene expression analysis to understand the molecular mechanisms underlying these features.
Additionally, we explore transgenerational transmission of parental phenotypes and epigenetic modifications, which may offer new insights into how organisms adapt to acute stresses and how such “memories” are passed to future generations. Our past research also includes efforts in plant disease resistance through genetic engineering of antimicrobial peptides to improve crop resilience.
Publications
See the most current publication list: https://www.ncbi.nlm.nih.gov/myncbi/1NakbGjH4ENcAp/bibliography/public/