Biology subjects

Woo, Y.

Publications and source records attributed to Woo, Y..

6 recordsLinked to original sources

bioRxiv2025

Identification of molecular mechanisms contributing to acquired thermotolerance by transcriptome profiling

Heat stress poses a serious threat to plant survival and productivity, and has a direct influence on crop yield stability. Plants response to high temperature is tightly controlled by complex genetic networks. Plants can be acclimated through gradual pre-exposure to increasing temperatures and that in turn causes higher survival in subsequent and otherwise lethal heat stress conditions. To investigate the physiological and molecular processes underlying heat acclimation and recovery, we examined changes in Arabidopsis thaliana transcriptome throughout the acclimation and the subsequent heat shock treatment. Groups of differentially expressed genes and enriched biological pathways that constitute the heat transcriptional memory were identified. The function of flavonoids in plant heat stress were further explored experimentally. In addition, we observed altered stomata density and aperture responses in heat acclimated plants, and this might be partially controlled by AGAMOUS-LIKE16 (AGL16) transcription factor and its negative regulator microRNA824 (miR824).

plant biology↗

bioRxiv2023

Integrated characterization of cell types, states and molecular programs in disseminated appendiceal neoplasms

Appendiceal neoplasms include a heterogeneous group of epithelial and non-epithelial tumors with varying malignant potential. Despite the rise in incidence of appendiceal neoplasms in recent years, limited progress has been made in the understanding, management and therapeutic treatment. To comprehensively characterize the cell types and molecular mechanisms driving cellular remodeling in epithelial appendiceal neoplasms, we performed an integrated scRNA-seq study. We analyzed 126,998 cells from 16 appendix samples (11 peritoneal metastases samples, 5 healthy controls) and identified 33 distinct cell types/cell states with seven being cancer-specific. Highlights of our study include the characterization of tumor cells across the histologic spectrum, the identification of a novel cancer-associated-fibroblast (CAF) subtypes (fiCAFs) and the identification of pathologic-specific cellular crosstalk between tumor cells and the tumor microenvironment (TME). Together, our study provides a high-resolution insight into the complexity and heterogeneity of epithelial appendiceal neoplasms and a valuable resource for therapeutic strategies.

genomics↗

bioRxiv2023

Different populations of midbrain neurons control the production of distinct acoustic categories of vocalization

Animals produce different acoustic types of vocalizations in different behavioral contexts. The midbrain periaqueductal gray (PAG) is obligatory for vocal production (Jurgens, 1994, 2002, 2009), but how midbrain circuits are organized to control the production of different vocalization types remains unknown. To test whether a single population of midbrain neurons regulates the production of different vocalization types, we applied intersectional methods to selectively ablate a population of midbrain neurons required for the production of ultrasonic vocalizations (USVs) in mice. We find that although ablation of these PAG-USV neurons blocks USV production in both males and females, these neurons are not required for the production of squeaks. Our findings provide strong evidence that distinct populations of midbrain neurons control the production of different acoustic categories of vocalizations.

neuroscience↗

bioRxiv2023

Antigen-dependent IL-12 signaling in CAR T cells promotes regional to systemic disease targeting

Chimeric antigen receptor (CAR) T cell therapeutic responses are hampered by limited T cell trafficking, persistence, and durable anti-tumor activity in solid tumor microenvironments. However, these challenges can be largely overcome by relatively unconstrained synthetic engineering strategies, which are being harnessed to improve solid tumor CAR T cell therapies. Here, we describe fully optimized CAR T cells targeting tumor-associated glycoprotein-72 (TAG72) for the treatment of solid tumors, identifying the CD28 transmembrane domain upstream of the 4-1BB co-stimulatory domain as a driver of potent anti-tumor activity and IFN{gamma} secretion. These findings have culminated into a phase 1 trial evaluating safety, feasibility, and bioactivity of TAG72-CAR T cells for the treatment of patients with advanced ovarian cancer (NCT05225363). Preclinically, we found that CAR T cell-mediated IFN{gamma} production facilitated by IL-12 signaling was required for tumor cell killing, which was recapitulated by expressing an optimized membrane-bound IL-12 (mbIL12) molecule on CAR T cells. Critically, mbIL12 cell surface expression and downstream signaling was induced and sustained only following CAR T cell activation. CAR T cells with mbIL12 demonstrated improved antigen-dependent T cell proliferation and potent cytotoxicity in recursive tumor cell killing assays in vitro and showed robust in vivo anti-tumor efficacy in human xenograft models of ovarian cancer peritoneal metastasis. Further, locoregional administration of TAG72-CAR T cells with antigen-dependent IL-12 signaling promoted durable anti-tumor responses against both regional and systemic disease in mice and was associated with improved systemic T cell persistence. Our study features a clinically-applicable strategy to improve the overall efficacy of locoregionally-delivered CAR T cells engineered with antigen-dependent immune-modulating cytokines in targeting both regional and systemic disease.

cancer biology↗

bioRxiv2022

Retinoic acid-induced protein 14 controls dendritic spine dynamics associated with depressive-like behaviors

Dendritic spines are the central postsynaptic machinery that determines synaptic function. The F-actin within dendritic spines regulates their dynamic formation and elimination. Rai14 is an F-actin-regulating protein with a membrane-shaping function. Here, we identified the roles of Rai14 for the regulation of dendritic spine dynamics associated with stress-induced depressive-like behaviors. Rai14-deficient neurons failed to maintain a proper dendritic spine density in the Rai14+/- mouse brain, resulting in impaired functional synaptic activity. Rai14 was protected from degradation by complex formation with Tara, and accumulated in the dendritic spine neck, thereby enhancing spine maintenance. Concurrently, Rai14 deficiency in mice altered gene expression profile relevant to depressive conditions and increased depressive-like behaviors. Moreover, Rai14 expression was reduced in the prefrontal cortex of the mouse stress model, which was blocked by antidepressant treatment. Thus, we propose that Rai14-dependent regulation of dendritic spines may underlie the plastic changes of neuronal connections relevant to depressive-like behaviors.

neuroscience↗

bioRxiv2020

Click-chemistry enabled directed evolution of glycosynthases for bespoke glycans synthesis

Engineering of carbohydrate-active enzymes like glycosynthases for chemoenzymatic synthesis of bespoke oligosaccharides has been limited by the lack of suitable directed evolution based protein engineering methods. Currently there are no ultrahigh-throughput screening methods available for rapid and highly sensitive single cell-based screening of evolved glycosynthase enzymes employing azido sugars as substrates. Here, we report a fluorescence-based approach employing click-chemistry for the selective detection of glycosyl azides (versus free inorganic azides) that facilitated ultrahigh-throughput in-vivo single cell-based assay of glycosynthase activity. This discovery has led to the development of a directed evolution methodology for screening and sorting glycosynthase mutants for synthesis of desired fucosylated oligosaccharides. Our screening technique facilitated rapid fluorescence activated cell sorting of a large library of glycosynthase variants (>106 mutants) expressed in E. coli to identify several novel mutants with increased activity for {beta}-fucosyl-azide activated donor sugars towards desired acceptor sugars, demonstrating the broader applicability of this methodology.

biochemistry↗