Biology subjects

Iida, M.

Publications and source records attributed to Iida, M..

7 recordsLinked to original sources

bioRxiv2026

A Novel Syngeneic Mouse Model to Study Immune Evasion in Head and Neck Squamous Cell Carcinoma

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, and patient outcomes have remained largely unchanged despite advances in multimodal therapy. Immune checkpoint inhibitors (ICIs), which block the PD-1/PD-L1 axis to restore T cell-mediated anti-tumor immunity, have emerged as a promising treatment strategy. However, response rates remain below 20% in HNSCC, underscoring the need to better understand mechanisms of immune evasion within the tumor microenvironment. Syngeneic mouse models are essential for studying tumor-immune interactions, yet currently available HNSCC models are limited. Here, we report the development of a novel FVB/NJ-derived syngeneic HNSCC model generated from 7,12-dimethylbenz(a)anthracene (DMBA)-induced primary on floor of mouth/buccal tumors, designated FMOC1, FMOC2, and FMOC3 (FVB/NJ Mouse Oral Cancer). In vitro, all FMOC cell lines exhibited robust proliferative capacity with distinct proliferation kinetics. In vivo, all FMOC cell lines exhibited characteristic HNSCC histopathology, including cytokeratin 5 positivity, and were tumorigenic in immunodeficient NCG mice; however, in syngeneic immunocompetent mice, only FMOC1 demonstrated sustained tumor growth at orthotopic and flank sites, whereas FMOC2 and FMOC3 tumors underwent spontaneous regression within 2 weeks, indicating differential immune-dependent tumorigenicity among the lines. Consistent with this, depletion of CD4+ and/or CD8+ T cells restored tumor growth in FMOC2 and FMOC3 models, indicating a critical role for T cell-mediated immunity in tumor suppression. Notably, FMOC1 tumors were responsive to anti-PD-L1 and anti-CTLA-4 therapy, supporting their utility for evaluating immunotherapeutic strategies. Collectively, these findings establish the FMOC model as a novel and versatile platform to study tumor-immune interactions and immune evasion mechanisms in HNSCC, with potential applications in preclinical immunotherapy development.

cancer biology↗

bioRxiv2025

Fern and gymnosperm SPCH/MUTE and FAMA can regulate multiple cell fate transitions during stomatal development

Stomatal development is driven by a conserved family of basic Helix-loop-helix (bHLH) transcription factors. In the angiosperm model Arabidopsis thaliana, SPEECHLESS (SPCH), MUTE and FAMA show pronounced yet incompletely separated stage-specific functions. How the functional specialization observed within angiosperms evolved has remained unclear. Here, we perform the first functional analysis of stomatal regulators from the fern Ceratopteris richardii and the gymnosperm Picea abies (Norway spruce). We show that both species possess a single SPCH/MUTE-like gene (CrSM and PaSM) together with a single FAMA-like gene (CrFAMA and PaFAMA). Cross-species complementation in Arabidopsis showed that all the four bHLHs displayed broad developmental capacities and promoted asymmetric stomatal-lineage entry divisions, a function associated with angiosperm SPCH. Moreover, PaSM promoted pore-like structure formation in the fama background, indicating a capacity extending into a developmental transition controlled by angiosperm FAMA. To examine the functions of PaSM and PaFAMA in the native context, we generated transgenic spruce lines expressing dominant-negative variants of these genes. Perturbation of either bHLH was associated with fewer epidermal cells between adjacent stomata, whereas the two constructs produced partially distinct effects on mature stomatal-complex morphology. Together, our findings show that the fern and gymnosperm stomatal bHLHs examined here possess broad and overlapping developmental capacities. These results support a model in which the stage-specific functions of angiosperm stomatal regulators evolved through the progressive refinement and partitioning of broader, partially overlapping developmental capacities.

plant biology↗

bioRxiv2024

Dysregulated expanded endocannabinoid system as therapeutic targets of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the selective loss of upper and lower motor neurons. ALS patients often manifest systemic metabolic abnormalities such as glucose intolerance. Herein, to elucidate the systemic metabolic changes related to ALS progression, we performed metabolomics analysis on the serum of ALS patients and identified several metabolites associated with the disease progression, including metabolites involved in the expanded endocannabinoid system (ECS). In particular, the levels of N-acyl taurines (NAT) were correlated with the longitudinal change in the revised ALS functional rating scale (ALSFRS-R) rating. In vitro experiments with ALS cell models and in vivo studies with SOD1G93A transgenic mice revealed that PF-04457845, a fatty amide acid hydrolase (FAAH) inhibitor, up-regulated the expanded ECS, particularly the levels of NATs and N-acyl ethanolamine and ameliorates motor neuron degeneration through the regulation of microglial polarization, synapse plasticity, and neuronal development. Our study indicates that dysregulation of the expanded ECS is associated with ALS progression and a target for novel disease-modifying therapies.

neuroscience↗

bioRxiv2024

Dysregulated synaptic gene expression in oligodendrocytes of spinal and bulbar muscular atrophy

Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disease caused by an expanded CAG repeat in the androgen receptor (AR) gene. To elucidate the cell type-specific temporal gene expression in SBMA, we performed single-nucleus RNA sequencing on the spinal cords of AR-97Q mice. Among all cell types, oligodendrocytes (OLs) had the highest number of differentially expressed genes before disease onset. Analysis of OL clusters suggested that pathways associated with cation channels and synaptic function were activated before disease onset, with increased output from OLs to neurons in AR-97Q mice compared to wild-type mice. These changes in the early stages were abrogated in the advanced stages. An OL cell model of SBMA showed phenotypes similar to those of AR-97Q mice at early stages, such as increased transcriptional changes in synapse organization. Our results indicate that the dysregulation of cell-to-cell communication has a major impact on the early pathology of SBMA and is a potential therapeutic target for SBMA.

neuroscience↗

bioRxiv2023

JUMP Cell Painting dataset: morphological impact of 136,000 chemical and genetic perturbations

Image-based profiling has emerged as a powerful technology for various steps in basic biological and pharmaceutical discovery, but the community has lacked a large, public reference set of data from chemical and genetic perturbations. Here we present data generated by the Joint Undertaking for Morphological Profiling (JUMP)-Cell Painting Consortium, a collaboration between 10 pharmaceutical companies, six supporting technology companies, and two non-profit partners. When completed, the dataset will contain images and profiles from the Cell Painting assay for over 116,750 unique compounds, over-expression of 12,602 genes, and knockout of 7,975 genes using CRISPR-Cas9, all in human osteosarcoma cells (U2OS). The dataset is estimated to be 115 TB in size and capturing 1.6 billion cells and their single-cell profiles. File quality control and upload is underway and will be completed over the coming months at the Cell Painting Gallery: https://registry.opendata.aws/cellpainting-gallery. A portal to visualize a subset of the data is available at https://phenaid.ardigen.com/jumpcpexplorer/.

bioinformatics↗

bioRxiv2022

Multi-modal brain magnetic resonance imaging database covering marmosets with a wide age range

Magnetic resonance imaging (MRI) is a noninvasive neuroimaging method beneficial for the identification of normal developmental and aging processes and data sharing. Marmosets have a relatively shorter life expectancy (approximately 10 years) than other primates, including, humans because they grow and age faster. Hence, the common marmoset model is effective in aging research. The current study investigated the aging process of the marmoset brain and provided an open MRI database on marmosets with a wide age range. The Brain/MINDS Marmoset Brain MRI Dataset contains brain MRI information on 216 marmosets aged between 1 and 10 years. During its release date, it is the largest public dataset worldwide. Further, it comprises multi contrast MRI images. In addition, 91 of 216 animals have corresponding ex vivo high-resolution MRI datasets. Our MRI database, which is available at the Brain/MINDS Data portal might help understand the effects of different factors, such as age, sex, body size, and fixation, on the brain. Moreover, it can contribute to and accelerate brain science studies worldwide.

neuroscience↗

bioRxiv2020

The Ephrin receptor A2 and Roundabout Guidance Receptor 1 heterodimer: A potential theranostic for squamous cell carcinomas

Squamous cell carcinomas (SCC) of the lung (LSCC) and head and neck (HNSCC) are very prevalent with poor prognosis and limited treatment options. In both cancer types, Ephrin receptor A2 (EPHA2) is known to be overexpressed and exhibit opposing effects via two distinct signaling mechanisms. While it can inhibit cancer cell survival and migration by ligand-dependent signaling through tyrosine kinase phosphorylation at Y588 and Y772, it can promote tumor progression and cell migration in a ligand-independent manner via phosphorylation at S897. Variable ABnormal morphology (VAB-1) is the C. elegans ortholog of the human ephrin receptor (EPHR) that interacts genetically and biochemically in a dose-dependent manner with the axon guidance receptor, SAX3, the worm ortholog of ROBO. Double mutants of vab-1(EPHR)/sx-3(ROBO) are synthetic lethal, underscoring the interaction between the two signaling pathways which prompted us to investigate their role in SCC. Using biochemical and biophysical techniques, we show that EPHA2 and ROBO1 reside in the same complex and interact physically to form a functional heterodimer in LSCC and HNSCC. Furthermore, we show that treating squamous cells with the SLIT2, ligand of ROBO1, hinders phosphorylation of EPHA2 at S897, and thereby, attenuates cell proliferation. Interestingly, SLIT2 can interact with EPHA2 and attenuate the proliferation of cells that have low ROBO1 expression. Additionally, SLIT2 can act synergistically with the EPHA2 inhibitor, Ensartinib to attenuate cell growth in LSCC and HNSCC cells. Taken together, the data suggest that SLIT2 may serve as a novel therapeutic for LSCC and HNSCC. Here, we propose to stratify patients for treatment with SLIT2 and/or Ensartinib, based on their EPHA2 and ROBO1 expression levels in the diseased tissue. Thus 85% of LSCC cases can be treated with combination of SLIT2+Ensartinib and 55% of HNSCC cases can be treated with either SLIT2 or Ensartinib. Furthermore, EPHA2 and ROBO1 may represent novel theranostics in these two diseases. One sentence summaryHeterodimerization of EPHA2 and ROBO1 receptors attenuates growth of squamous cell carcinomas of the lung and head and neck.

cancer biology↗