Biology subjects

Haba, H.

Publications and source records attributed to Haba, H..

3 recordsLinked to original sources

bioRxiv2026

A fungal phosphate starvation regulator gates virulence to prioritize nutrient adaptation in response to host phosphate status

Plant-associated microbes must constantly balance environmental adaptation with virulence to survive in fluctuating ecosystems, yet the molecular mechanisms coupling these processes remain poorly understood. Here, we identify NUTRIENT-DEPENDENT FACILITATOR OF COLONIZATION1 (NFC1), a virulence factor in a conditionally pathogenic Colletotrichum tofieldiae strain, whose expression is tightly regulated by both temperature and phosphate availability. Leveraging plant phosphate starvation response (PSR) mutants and direct phosphate supplementation to host plants, we demonstrate that NFC1 expression is driven by the internal phosphate status of the host rather than environmental availability alone. Notably, the fungal PSR regulator CtPHO4 represses NFC1 and virulence during phosphate starvation, while simultaneously activating canonical fungal PSR-related genes. Conversely, under phosphate sufficiency, NFC1 is strongly induced and promotes infection, potentially by modulating the host circadian clock system. This study uncovers a molecular link between metabolic adaptation and virulence programming, providing a conceptual framework for predicting disease dynamics under changing environments.

microbiology↗

bioRxiv2025

Novel therapy for gastric cancer peritoneal dissemination using genetically modified dental pulp cells and astatine-211

Peritoneal dissemination of gastric cancer is a terminal stage with limited treatment options and a five-year survival rate below 10%. To develop a more effective treatment, we created a new approach that uses genetically engineered human dental pulp cells (DPCs) that express the sodium/iodide symporter (NIS). These cells (NIS-DPCs) deliver astatine-211 (At-211) directly to tumor sites. When injected intraperitoneally into a mouse model of gastric cancer dissemination, DPCs, which were isolated and expanded, showed strong tumor-homing ability. Chemotaxis mediated by the CXCR4/SDF-1 axis has been reported to play a role in this accumulation. In addition to histological analysis, fluorescent imaging confirmed the selective accumulation of NIS-DPCs within tumor lesions. Introducing the NIS gene markedly increased SLC5A5 expression, enabling efficient At-211 uptake. To avoid nonspecific binding, sodium At-211 was utilized. High-resolution alpha-particle imaging visualized alpha-ray emission specifically from NIS-DPCs, confirming the radionuclides intracellular retention. In vivo, the sequential administration of NIS-DPCs, followed by Na[At-211], resulted in the pronounced regression of peritoneal tumors and a significant extension of survival compared to controls. The therapeutic mechanism involves three coordinated steps: tumor-directed migration of NIS-DPCs, At-211 uptake via NIS transporters, and localized alpha-particle-mediated cytotoxicity. This study introduces the novel concept of cell-based alpha-radiotherapy, which integrates regenerative and nuclear medicine. Due to the well-documented safety profile of DPCs in human clinical trials (J-REPAIR, jRCT1080224505), the NIS-DPC platform emerges as a promising approach for the precise, localized irradiation of disseminated gastric cancer and other challenging malignancies.

cancer biology↗

bioRxiv2024

A fungal transcription factor BOT6 facilitates the transition of a beneficial root fungus into an adapted anthracnose pathogen

The infection strategies employed by plant endophytes are attributed to their ability to overcome durable nonhost resistance and adapt to the host environment. However, the regulatory genetic background underlying how they adapt to the host and determine their lifestyles remains enigmatic. Here, we show that the CtBOT6, a cluster-residing transcription factor in the root-associated fungus Colletotrichum tofieldiae (Ct), plays a pivotal role in regulating virulence-related gene expression and in producing metabolites both not only within and but unexpectedly outside of the cluster. Genetic manipulation of CtBOT6 toward activation alone is sufficient to transition a root beneficial Ct along the mutualist-pathogen continuum even toward a leaf pathogen capable of overcoming nonhost resistance, partly dependent on the host abscisic acid and ethylene pathways. Our findings indicate that the status of CtBOT6 serves as a critical determinant for the endophytic fungus to adapt to the plant different environments and manifest diverse infection strategies.

plant biology↗