Biology subjects

Luu, S.

Publications and source records attributed to Luu, S..

3 recordsLinked to original sources

bioRxiv2026

Self-Interaction Nanoparticle Spectroscopy Predicts High-Concentration Viscosity of Therapeutic IgG1 Antibodies

Predicting high-concentration viscosity of monoclonal antibodies such as IgG1 is crucial for their development as therapeutics for subcutaneous delivery. Unfortunately, traditional experimental rheometry methods for assessing viscosity are low-throughput. This study evaluates Self-Interaction Nanoparticle Spectroscopy (SINS) assays--specifically charge-stabilized SINS (CS-SINS) and PEG-stabilized SINS (PS-SINS)--for high-throughput viscosity prediction. We characterized 96 IgG1 antibodies, assessing SINS against in silico descriptors and dynamic light scattering (DLS) data. CS-SINS showed strong correlation with charge, offering limited additional utility. In contrast, PS-SINS provided orthogonal information; integrating it with in silico data and DLS significantly improved random forest model accuracy for binary viscosity classification. PS-SINS measurements in multiple buffers captured complementary information, achieving comparable accuracy without DLS. Importantly, PS-SINS scores exhibited a strong logarithmic relationship (r=0.98) with high-concentration viscosity in Fc variants of clinical antibodies, suggesting a direct mechanistic link. Furthermore, PS-SINS performed reliably with one column purified (protein A) samples, supporting its early-stage application. These findings establish PS-SINS as a high-throughput tool to accelerate the developability assessment of antibody candidates.

biochemistry↗

bioRxiv2021

A Novel Ex Vivo Peritoneal Model to Investigate Mechanisms of Peritoneal Metastasis in Gastric Adenocarcinoma

Peritoneal metastases (PM) portend limited survival in patients with Gastric Adenocarcinoma (GCa), and strategies to prevent and/or more effectively treat PM are needed. Existing models are limited in recapitulating key elements of the peritoneal metastatic cascade. To explore the underlying cellular and molecular mechanisms of PM, we have developed an ex vivo human peritoneal explant model. Fresh peritoneal tissue samples were obtained from patients undergoing abdominal surgery and suspended, mesothelial layer down but without direct contact, above a monolayer of red-fluorescent stained AGS human GCa cells for 24hrs, then washed and cultured for a further 3 days. Implantation and invasion of GCa cells within the explant were examined using real-time confocal fluorescence microscopy. Superficial implantation of AGS GCa cells within the mesothelial surface was readily detected, and colonies expanded over 3 days. To investigate the sensitivity of the model to altered GCa cellular implantation, we stably transfected AGS cells with E-Cadherin, restoring the E-Cadherin that they otherwise lack. This markedly suppressed implantation and invasion of AGS cells into the submesothelial mesenchymal layer. Here we show that this ex vivo human peritoneal explant model is responsive to manipulation of genetic factors that regulate peritoneal implantation and invasion by GCa cells, with reproducible results.

cancer biology↗

bioRxiv2020

Astroglial Calcium Signaling Encodes Sleep Need in Drosophila

Sleep is under homeostatic control, whereby increasing wakefulness generates sleep need and triggers sleep drive. However, the molecular and cellular pathways by which sleep need is encoded are poorly understood. In addition, the mechanisms underlying both how and when sleep need is transformed to sleep drive are unknown. Here, using ex vivo and in vivo imaging, we show in Drosophila that astroglial Ca2+ signaling increases with sleep need. We demonstrate that this signaling is dependent on a specific L-type Ca2+ channel and is required for homeostatic sleep rebound. Thermogenetically increasing Ca2+ in astrocytes induces persistent sleep behavior, and we exploit this phenotype to conduct a genetic screen for genes required for the homeostatic regulation of sleep. From this large-scale screen, we identify TyrRII, a monoaminergic receptor required in astrocytes for sleep homeostasis. TyrRII levels rise following sleep deprivation in a Ca2+-dependent manner, promoting further increases in astrocytic Ca2+ and resulting in a positive-feedback loop. These data suggest that TyrRII acts as a gate to enable the transformation of sleep need to sleep drive at the appropriate time. Moreover, our findings suggest that astrocytes then transmit this sleep need to the R5 sleep drive circuit, by upregulation and release of the interleukin-1 analog Spatzle. These findings define astroglial Ca2+ signaling mechanisms encoding sleep need and reveal dynamic properties of the sleep homeostatic control system.

neuroscience↗