Biology subjects

DUARTE, V.

Publications and source records attributed to DUARTE, V..

3 recordsLinked to original sources

bioRxiv2026

Reprogramming CAR-T cell function through synthetic cytokine receptors suppresses metastatic progression of TNBC

Patient T cells modified with chimeric antigen receptors (CARs) have shown remarkable therapeutic success in previously incurable cancers. However, despite its success in hematological malignancies, CAR-T therapy has shown only modest efficacy in solid tumors. The medical field has focused on developing new molecular designs that enhance CAR-T persistence, prevent exhaustion in the tumor microenvironment (TME), and increase the specificity of the CAR-T cell to various tumor antigens. However, much less effort has been placed on enhancing CAR-T cells' invasion into and migration through the stromal matrix of the TME, where they can elicit tumor-directed cytotoxicity. Here, we engineered CAR-T cells with synthetic cytokine receptors targeting inflammatory cytokines produced by the cells themselves, which increase their speed through collagen I matrices. We show that this enhanced motility is driven by increased CAR-T cell translocation through confined microchannels via cellular deformation, together with elevated migratory speeds in proximity to neighboring cells, suggesting improved responsiveness to local cues. These migration-enhanced CAR-T cells significantly reduce both primary tumor size and distant organ metastasis in triple-negative breast cancer (TNBC) mouse models compared to standard CAR-T cells. These results support molecular design strategies that exploit mechanisms to improve cellular therapies for metastatic solid tumors.

bioengineering↗

bioRxiv2026

The broad-spectrum RumC1 bacteriocin targets a transient peptidoglycan intermediate of the nascent cell wall

RumC1 is a structurally unique bacteriocin with broad-spectrum efficacy, including against multidrug-resistant pathogens, yet acting by an undefined mechanism. By integrating genetics, biochemistry, computational modeling and single-cell fluorescence microscopy, we demonstrate that RumC1 is a distinct cell-wall-targeting toxin. First, all RumC1-resistant mutants isolated through a high-rate, genome-wide mutagenic screening exhibited specific impairments in peptidoglycan homeostasis regulation, pinpointing this pathway as critical for RumC1 activity. Second, RumC1 selectively accumulates within neosynthesized peptidoglycan, leading to cell growth arrest and death in a dose-dependent manner. Third, we characterize the RumIc1 immunity protein of the RumC1 biosynthetic cluster as a peptidase acting at the cell surface to protect the cells by trimming the stem peptide crucial for cell-wall assembly. As such, RumIc1 provides cross-protection against vancomycin, while RumC1 is demonstrated to act differently from this glycopeptide antibiotic. Collectively, these findings establish RumC1 as a toxin targeting a key peptidoglycan intermediate of cell wall maturation.

microbiology↗

bioRxiv2025

3D map-guided modeling of functional endometrial tissue using multi-compartment assembloids

The human endometrium is a dynamic tissue that lines the uterus and undergoes constant remodeling, making it especially susceptible to gynecological diseases like endometriosis and endometrial cancer. The molecular mechanisms of these conditions are not well understood, partly due to the lack of in vitro models that mimic endometrial physiology, which limits options for targeted intervention and treatment of these diseases. Mouse models are also inadequate, as common laboratory strains do not naturally undergo a menstrual cycle comparable to that of humans. This study addresses this need by developing a 3D multi-compartment assembloid that mimics the architecture of endometrial tissue and recapitulates all three phases of the menstrual cycle (proliferative, secretory, and menstrual regression) within a single platform. The cellular and extracellular matrix (ECM) components in each compartment are carefully tuned based on a 3D spatial cellular map of endometrial tissue. The model contains endometrial epithelial cells enveloped in a basement membrane and endometrial stromal cells in a surrounding collagen-rich layer; this architecture allows realistic interactions between these cells and their respective ECMs. This assembloid successfully supports the controlled growth and organization of these cells, revealing reciprocal regulation of cell behavior and exhibiting compartment-specific hormonal responses, i.e., stromal decidualization. This platform enables the study of dynamic, phase-resolved, and compartment-specific paracrine signaling in human endometrial biology. By combining tissue-informed design, modular fabrication, and full-cycle hormonal responsiveness, this model sets a new benchmark for blastocyst implantation studies, organ modeling, and precision diagnostics in human reproductive health.

bioengineering↗