Biology subjects

Khatun, S.

Publications and source records attributed to Khatun, S..

3 recordsLinked to original sources

bioRxiv2026

Targeting the TRA-1-60 Glycoepitope Enables Selective ImmunoPET Imaging of Ovarian Cancer

Targeted radiopharmaceutical development for ovarian cancer (OC) has been limited by the lack of molecular targets that combine broad tumor expression with minimal normal-tissue distribution. TRA-1-60 (TRA) is a cancer-associated glycoepitope carried by podocalyxin. Here, we evaluated TRA as a target for OC and developed a TRA-directed immunoPET imaging platform. Immunohistochemical analysis demonstrated significantly higher TRA expression in ovarian tumors than in normal adjacent ovarian tissue, with expression maintained across epithelial OC histotypes and disease stages. An engineered anti-TRA single-chain variable fragment-Fc (scFv-Fc) demonstrated robust penetration of three-dimensional tumor spheroids and selective accumulation in intraperitoneal tumors in an immunocompetent syngeneic OC model. Radiolabeling with zirconium-89 generated [Zr]Zr-DFO-anti-TRA scFv-Fc with >98% radiochemical yield. Serial PET/CT imaging demonstrated progressive and sustained radiotracer accumulation at tumor sites through 96 hours, accompanied by declining liver-associated activity and low uptake in most normal tissues. Together, these findings identify TRA as a broadly expressed and accessible tumor-associated glycoepitope and establish TRA-targeted immunoPET as a promising strategy for noninvasive detection of OC. The selective and sustained tumor localization of this platform further provides a foundation for development of TRA-directed radiopharmaceutical therapy, supporting a potential theranostic approach for OC.

cancer biology↗

bioRxiv2025

Granular component sub-phases direct ribosome biogenesis in the nucleolus

The hierarchical, multiphase organization of the nucleolus underlies ribosome biogenesis. Ribonucleoprotein particles that regulate ribosomal subunit assembly are heterogeneously disposed in the granular component (GC) of the nucleolus. However, the molecular origins of the GCs spatial heterogeneity and its association with ribosomal subunit assembly remain poorly understood. Here, using super-resolution microscopy, we uncover that key GC biomolecules, including nucleophosmin (NPM1), surfeit locus protein 6 (SURF6), and ribosomal RNA (rRNA), are heterogeneously localized within sub-phases in the GC. In vitro reconstitution showed that these GC biomolecules form multiphase condensates with SURF6/rRNA-rich core and NPM1-rich shell, providing a mechanistic basis for GCs spatial heterogeneity. SURF6s association with rRNA is weakened upon ribosome subunit assembly, enabling NPM1 to extract assembled subunits from condensates--suggesting an assembly-line-like mechanism of subunit efflux from the GC. Our results establish a framework for understanding the heterogeneous structure of the GC and reveal how its distinct sub-phases facilitate ribosome subunit assembly.

biochemistry↗

bioRxiv2020

Gold-standard diagnostics are tarnished by lytic bacteriophage

BackgroundA fundamental clinical and scientific concern is how lytic bacteriophage, as well as antibiotics, impact diagnostic positivity. MethodsCholera was chosen as a model disease to investigate this important question. Patients with diarrheal disease were enrolled at two remote hospitals in Bangladesh. Diagnostic performance was assessed as a function of lytic bacteriophage detection, as well as exposure to the first-line antibiotic azithromycin detected by mass spectrometry. ResultsAmong diarrheal samples positive by nanoliter quantitative PCR for Vibrio cholerae (n=78/849), the odds that a rapid diagnostic test (RDT) or qPCR was positive was reduced by 89% (OR 0.108; 95%CI 0.002-0.872) and 87% (OR 0.130; 95%CI 0.022-0.649) when lytic bacteriophage were detected, respectively. The odds that a rapid diagnostic test (RDT) or qPCR was positive was reduced by more than 99% (OR 0.00; 95% CI: 0.00-0.28) and 89% (OR 0.11; 95% CI: 0.03-0.44) when azithromycin was detected, respectively. ConclusionsEstimations of cholera burden may improve by accommodating for the negative effect of antimicrobial exposure on diagnostic positivity. Furthermore, the findings herein challenge our current approach to interpreting and developing bacterial diagnostics given variable rates of lytic bacteriophage and antibiotic exposure.

microbiology↗