Biology subjects

Ulukan, B.

Publications and source records attributed to Ulukan, B..

3 recordsLinked to original sources

bioRxiv2026

Lysyl oxidase drives ccRCC progression by coordinating HIF-2α transcription program with tumor microenvironment

Clear cell renal cell carcinoma (ccRCC) is driven by persistent HIF-2 transcription program initiated by VHL loss, yet molecular mediators sustaining this program are poorly defined. Using single-cell transcriptomics, we identified lysyl oxidase (LOX) as a driver of ccRCC progression, selectively enriched in a hypoxia/epithelial-mesenchymal transition (EMT) gene program associated with poor outcome. While LOX oxidizes and stabilizes HIF-2 by antagonizing HUWE1-mediated ubiquitination and degradation, thereby sustaining HIF-2-driven transcription in cancer cells, it also remodels extracellular matrix (ECM) and promotes angiogenesis in the tumor microenvironment (TME). Genetic or pharmacological inhibition of LOX destabilizes HIF-2, disrupts ECM, inhibits angiogenesis, and suppresses tumor initiation, growth, and metastasis in vivo. LOX inhibition enhances anti-angiogenic therapy response and remains effective in belzutifan-resistant HIF-2 G323E-mutant tumors. Nuclear LOX protein correlates with nuclear HIF-2 in high-grade patient tumors. Together, LOX coordinates HIF-2 transcription program with TME and is a therapeutic target in ccRCC.

cancer biology↗

bioRxiv2025

Single-Cell Microwave Cytometry for Drug Resistance Detection in Cancer

Monitoring biophysical changes in single cells induced by drugs is crucial for advancing cancer therapies, especially for highly heterogeneous tumours. Emerging methods for single-cell drug sensitivity testing have largely relied on phenomenological analyses. Here, we present a novel electronic cytometry platform integrating microwave resonators with impedance cytometry, enabling simultaneous, label-free measurements of cell volume and dielectric permittivity at microwave frequencies. This approach uniquely captures intracellular differential responses indicative of drug-induced biophysical states, thus providing deeper insights beyond traditional phenomenological analyses. We first validated the platform using varying salt concentrations. We then demonstrated that the sensor platform could differentiate between drug resistant versus sensitive phenotypes in multiple isogenic cancer cell lines treated with cytostatic, cytotoxic and mixed-effect drugs. Notably, we showed that the technique performs successfully in patient-derived tumor organoids, a model system highlighting its immediate clinical relevance. Our findings underscore the potential of electronic measurements at the single cell level to provide informative and actionable biophysical signals relating to cellular drug response. The implementation of this platform could significantly advance cancer treatment by identifying the resistant cell populations in heterogenous tumours and optimizing selection of drugs for each patient, paving the way towards precision medicine.

bioengineering↗

bioRxiv2025

CD20+ natural killer cells are polyfunctional, memory-like cells that are enriched in inflammatory disorders

While CD20 was initially characterized as a B cell-specific marker, its expression on memory T cells has expanded our understanding of this molecules distribution and function. Here, we identify a previously unrecognized CD20-expressing NK cell population and demonstrate its functional significance. CD56+CD20+ NK cells exhibit hallmarks of cellular activation, including elevated NKp46, CD69, and CD137 expression, enhanced proliferative capacity, and increased production of inflammatory cytokines (IFN-{gamma}, GM-CSF, TNF-, IL-10). Functional analyses revealed enhanced cytotoxicity against K562 targets, correlating with increased expression of cytolytic mediators including granzymes A, B, and K, perforin, FASL, and TRAIL. Single-cell transcriptional profiling demonstrated that MS4A1-expressing NK cells possess a distinct molecular signature characterized by elevated granzyme K expression and memory-like features. These cells preferentially localize to secondary lymphoid organs and accumulate in inflammatory tissues. Notably, CD56+CD20+ NK cells are enriched in multiple inflammatory conditions, including multiple sclerosis, autoimmune hepatitis, hepatitis B infection, hepatocellular carcinoma, and lung cancer. Treatment with rituximab depletes this population, suggesting potential therapeutic implications. Our findings establish CD20+ NK cells as a functionally distinct lymphocyte subset with enhanced effector capabilities and tissue-homing properties, providing new insights into immune regulation in inflammatory diseases. One Sentence SummaryOur study reveals expression of CD20 by NK cells, in relation with enhanced functionality, memory-like features, and inflammation.

immunology↗