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Pillar, N.

Publications and source records attributed to Pillar, N..

3 recordsLinked to original sources

Single-section multiplexed imaging enables comprehensive lung cancer diagnosis

Accurate and timely diagnosis is essential for effective lung cancer treatment. However, contemporary workflows rely on sequential immunohistochemistry of small biopsy specimens, which can exhaust tissue, limit biomarker assessment, and delay treatment decisions. Here, we demonstrate that multiplexed imaging addresses these limitations by enabling comprehensive lung cancer diagnosis from a single tissue section. We developed and validated a clinically informed multiplexed antibody panel that integrates tumor classification, predictive biomarker assessment, and immune profiling. In diagnostic biopsies, multiplexed imaging achieved 96% concordance with standard pathology, while enabling accurate automated PD-L1 scoring and rapid detection of clinically approved and emerging actionable targets. Simultaneously measuring dozens of proteins improves standard pathology by incorporating complex multi-protein biomarkers, supporting quantitative computational analysis to streamline diagnosis, and generating spatial data for translational research. By reducing turnaround time and preserving scarce tissue, this workflow has the potential to accelerate treatment decisions, improve patient outcomes and bridge clinical care with translational discovery.

cancer biology↗

2-hydroxyglutarate controls centromere and heterochromatin conformation and function in the male germline

2-hydroxyglutarate (2HG) is recognized as an epigenetic regulator in cancer and some transient biological processes. Of all organs, the testis harbors the highest baseline physiological levels of 2HG, yet its putative functions in germ cell biology are unknown. Here we show that 2HG is generated in specific stages of spermatogenesis by the testis specific lactate dehydrogenase C (LDHC), beginning at the last stages of prophase I. Unexpectedly LDHC enters nuclei and concentrates in centromeres. LDHC-generated L-2HG controls centromere condensation and pericentromeric heterochromatin organization through multiple effects including clustering of chromocenters, centromere and chromocenter condensation and expression of satellite RNAs. These effects are rapid and specific to L but not D-2HG. In vivo depletion of L-2HG causes centromere malfunction and activation of the spindle assembly checkpoint. Our findings reveal that 2HG can directly affect centromere and pericentromeric heterochromatin conformation and function and is necessary for licensing chromosome segregation.

cell biology↗

Dihydropyrimidinase-like 2 (DPYSL2) regulates breast cancer migration via a JAK/STAT3/vimentin axis

The intricate neuronal wiring during development requires cytoskeletal reorganization orchestrated by signaling cues. Considering that cytoskeletal remodeling is a hallmark of cell migration, we inquired whether metastatic cancer cells exploit the axon guidance proteins to migrate. Indeed, in breast cancer patients, we found a significant correlation between the mesenchymal markers and the expression of dihydropyrimidinase-like 2 (DPYSL2), a regulator of cytoskeletal dynamics in growing axons. Strikingly, DPYSL2 knockout in mesenchymal-like cells profoundly inhibited cell migration, invasion, stemness features, tumor growth rate, and metastasis. Next, we aimed to decode the molecular mechanism underlying this phenomenon and revealed an interaction between DPYSL2 and Janus kinase 1 (JAK1). This binding is crucial for triggering signal transducer and activator of transcription 3 (STAT3) and subsequently expressing vimentin, the pro-migratory intermediate filament. Collectively, we identified DPYSL2 as a molecular link between oncogenic signaling pathways and cytoskeletal reorganization in migrating breast cancer cells. Statement of significanceThis study shows that the axon guidance adaptor protein DPYSL2 is essential for promoting breast cancer migration. Specifically, this protein interacts with JAK1 to govern STAT3 signaling and subsequently vimentin expression.

cancer biology↗