Biology subjects

Tsui, M.

Publications and source records attributed to Tsui, M..

4 recordsLinked to original sources

bioRxiv2026

A single-cell and spatial atlas of prostate cancer reveals the combinatorial nature of gene modules underlying lineage plasticity and metastasis

Prostate cancer encompasses a spectrum of disease states driven by complex cellular heterogeneity. To delineate the transcriptional programs underlying lineage plasticity and metastasis, we constructed a comprehensive single-cell atlas of 128 patients, spanning localized, castration-resistant, and metastatic disease. Lineage plasticity was prevalent in localized disease, with subsets of tumor cells adopting distinct basal-like and club-like states. Luminal-like cancer cells also displayed extensive lineage infidelity, defined not by a binary loss of identity but by the combinatorial erosion of luminal gene modules associated with higher grade and stage. In the metastatic setting, gene program association analysis (GPAS) identified a broad induction of cell-cycle gene modules across organ sites as well as an induction of organ-specific gene modules, including osteomimetic signaling in bone, neuro-migratory genes in brain, and erythroid-like transitions in liver. Neuroendocrine prostate cancers (NEPCs) were not monolithic but defined by combinations of NE-associated gene modules including a novel HES6 program. Notably, these modules were detected at intermediate levels in localized samples, suggesting molecular plasticity precedes histological transformation. We also developed a refined NE signature that could distinguish NEPC tumors more accurately than previously published signatures. Within the tumor microenvironment (TME), we observed an elevation of pro-inflammatory Th17 T-cells in African American patients and identified a rare Schwann cell population. Finally, we present PCformer, a transformer-based foundation model trained on >500,000 cells to automate cell-state classification. Together, this comprehensive atlas demonstrates the complex nature of gene modules underlying lineage infidelity and plasticity in cancer cells and highlights distinct immune and stromal populations within the tumor ecosystem.

genomics↗

bioRxiv2025

Synthetic derivatives of vinpocetine as antiproliferative agents

Vincamine is an indole alkaloid initially isolated from plants of the Vinca genus and has previously been demonstrated to have antioxidant, hypoglycemic, and hypolipidemic activities. Vinpocetine, a synthetic derivative of vincamine with an enhanced pharmacological profile, has demonstrated promising antiproliferative properties. While previously reported vinpocetine derivatives have undergone extensive investigation for their pharmacological properties, the role of the E-ring ethyl ester in the anticancer properties of compounds with this scaffold has not yet been fully described. Here, we report the antiproliferative activity of two vinpocetine analogs with modifications at the E-ring. MTT assays revealed that reduction of the ethyl ester to an alcohol exhibited strong dose-dependent antiproliferative activity across five mammalian cell lines, but did not induce significant markers of apoptosis or necrotic death as determined by FITC/Annexin V and cell cycle flow cytometry, respectively. We further observe that vinpocetine and both analogs exhibit dose-dependent modulation of a TCF/LEF reporter cell, which appears to be decoupled from trends in antiproliferative activity Altogether, this work demonstrates the potential for E-ring modifications of vinpocetine as anticancer agents.

cancer biology↗

bioRxiv2021

Single-cell analysis of hepatoblastoma identifies distinct tumor cell signatures that predict susceptibility to chemotherapy using patient-specific tumor spheroids

Pediatric hepatoblastoma (HB) is the most common primary liver cancer in infants and children. Studies of HB that focus exclusively on tumor cells demonstrate sparse somatic mutations and a common cell of origin, the hepatoblast, across patients. In contrast to the homogeneity these studies would suggest, HB tumors have a high degree of heterogeneity that can portend poor prognosis. In this study, we used single-cell genomic techniques to analyze resected human pediatric HB specimens. This study establishes that tumor heterogeneity can be defined by the relative proportions of five distinct subtypes of tumor cells. Notably, patient-derived HB spheroid cultures predict differential responses to treatment based on the transcriptomic signature of each tumor, suggesting a path forward for precision oncology for these tumors. Collectively, these results define HB tumor heterogeneity with single-cell resolution and demonstrate that patient-derived spheroids can be used to evaluate responses to chemotherapy.

cancer biology↗

bioRxiv2018

Tissue repair in the mouse liver following acute carbon tetrachloride depends on injury-induced Wnt/β-catenin signaling

In the liver, Wnt/{beta}-catenin signaling is involved in regulating zonation and hepatocyte proliferation during homeostasis. We have examined Wnt gene expression and signaling after injury and we show by in situ hybridization that Wnts are activated by acute carbon tetrachloride (CCl4) toxicity. Following injury, peri-injury hepatocytes become Wnt-responsive, expressing the Wnt target gene Axin2. Lineage tracing of peri-injury Axin2+ hepatocytes shows that during recovery, the injured parenchyma becomes repopulated and repaired by Axin2+ descendants. Using single cell RNA sequencing (scRNA-seq), we show that endothelial cells are the major source of Wnts following acute CCl4 toxicity. Induced loss of {beta}-catenin in peri-injury hepatocytes results in delayed repair and ultimately to injury-induced lethality, while loss of Wnt production from endothelial cells leads to a delay in the proliferative response after injury.\n\nConclusionOur Pindings highlight the importance of the Wnt/{beta}-catenin signaling pathway in restoring tissue integrity following acute liver toxicity and establishes a role of endothelial cells as an important Wnt-producing regulator of liver tissue repair following localized liver injury.

developmental biology↗