Biology subjects

Tabury, K.

Publications and source records attributed to Tabury, K..

3 recordsLinked to original sources

bioRxiv2026

Heterogeneous and conserved radiation responses reveal FOXM1-dependent regulation of microcephaly genes in glioblastoma

Glioblastoma (GBM) is characterized by marked heterogeneity, glioma stem-like cells (GSCs), and resistance to therapy. Because GSCs share features with neural progenitor cells (NPCs), we investigated whether neurodevelopmental programs contribute to their response to irradiation. Transcriptional profiling of four patient-derived GSC lines revealed cell line-specific responses, with radiosensitivity correlating with the magnitude of p53 activation and basal expression of its negative regulator, MDM2. Despite this heterogeneity, radiation consistently activated p53-dependent pathways and suppressed cell-cycle programs. Among these, genes associated with primary hereditary microcephaly (MCPH) that regulate NPC proliferation were coordinately repressed. Single-cell RNA sequencing localized this response to G2/M-cycling cells. FOXM1 was similarly reduced following irradiation, emerged as a candidate regulator of a subset of MCPH genes, and correlated with their expression in GBM tumors. Pharmacological inhibition of FOXM1 reduced expression of selected MCPH genes and enhanced radiosensitivity in U251 cells. Together, these findings identify coordinated suppression of a FOXM1-associated MCPH program as part of the GBM radiation response, while suggesting that the radiosensitizing effects of pharmacological FOXM1 inhibition extend beyond this transcriptional axis.

cancer biology↗

bioRxiv2026

ReCardioids: a robust human heart organoid platform to model doxorubicin- and radiotherapy-induced cardiotoxicity

As global cancer incidence rises, so does the population of cancer survivors, making long-term and post-treatment quality of life a central clinical concern. Despite modern improvements in treatment, cardiotoxic side effects caused by anthracycline agents and thoracic radiotherapy remain a major clinical challenge. Human iPSC-derived heart organoids offer a promising alternative to animal and 2D in vitro models, but their utility is limited by inter-organoid variability. To address this, we developed reCardioids, a robust heart organoid model generated by dissociation and reaggregation of self-assembling cardioids. Through single-cell transcriptomics, we demonstrated that reCardiods maintain cellular diversity while also exhibiting a more mature cardiomyocyte phenotype compared to non-dissociated cardioids. To validate their utility as a preclinical in vitro model, we evaluated their response after exposure to doxorubicin and clinically relevant doses of {gamma}-radiation. reCardioids successfully modeled doxorubicin-induced cytotoxicity, metabolic decline and altered contractile dynamics. Bulk RNA sequencing following radiation exposure revealed a temporal trajectory of injury, progressing from acute DNA damage through vascular stunting, metabolic dysfunction and eventually compensatory pathological hypertrophic remodeling.

bioengineering↗

bioRxiv2022

PVT1, a YAP1 dependent stress responsive lncRNA drives ovarian cancer metastasis and chemoresistance

Metastatic growth of ovarian cancer cells into the peritoneal cavity requires adaptation to various cellular stress factors to facilitate cell survival and growth. Here we demonstrate the role of PVT1, one such stress induced long non-coding RNA, in ovarian cancer growth and metastasis. PVT1 is an amplified and overexpressed lncRNA in ovarian cancer with strong predictive value for survival and response to targeted therapeutics. We find that expression of PVT1 is regulated by ovarian tumor cells in response to cellular stress, particularly loss of cell-cell contacts and changes in matrix rigidity occurring in a YAP1 dependent manner. Induction of PVT1 promotes tumor cell survival, growth, and migration. Conversely, reducing PVT1 levels robustly abrogates metastatic behavior and tumor cell dissemination in cell lines and syngeneic transplantation models in vivo. We find that reducing PVT1 causes widespread transcriptome changes leading to alterations in cellular stress response and metabolic pathways including doxorubicin metabolism, which directly impacts chemosensitivity. Together, these findings implicate PVT1 as a promising therapeutic target to suppress metastasis and avoid chemoresistance in ovarian cancer. SUMMARY BLURBPVT1 is a stress-responsive IncRNA regulated by YAP1, leading to increased ovarian cancer metastasis and chemoresistance, making PVT1 a promising therapeutic target.

cancer biology↗