Biology subjects

Simoes, C. C.

Publications and source records attributed to Simoes, C. C..

6 recordsLinked to original sources

bioRxiv2026

Breedbase 2.0 - expanding the functionality for traditional breeding and transgenics

Breedbase ( is a comprehensive, web-based, open-source breeding management and analysis software for plant breeding that was introduced to address gaps with existing software for plant breeding data. Breedbase is continually improved and developed, with new features being added as required by the breeding community. Since its inception, the capabilities of Breedbase were improved to better serve the diverse data modeling needs of additional crops beyond our original ensemble of cassava, banana, yam, sweet potato, tomato, rice, and wheat. We describe here major updates that have been made in the past 4 years, including (1) improved handling of repetitive measurements; (2) a redesigned experimental treatments interface; (3) a more fine-grained user permission system; (4) improved trial quality control workflows; (5) intercropping support; (6) the addition of a decision meeting feature that helps decision makers make the best selection with the available data; (7) transgenics and tracking tools and finally, (8) an improved field layout tool which consolidates several trials in one field. These new features integrate seamlessly with the previous feature set of Breedbase - making it one of the most feature rich breeding management softwares available.

bioinformatics↗

bioRxiv2025

Pancreatic tumor microenvironment reprogramming via alloantigen-expressing virotherapy elicits tumor rejection and improves immunotherapy response

Pancreatic ductal adenocarcinoma (PDAC), the most common malignant type of pancreatic cancer, is characterized by a dense desmoplastic stroma, low neoantigen burden, and a highly immunosuppressive tumor microenvironment (TME), which severely limit cytotoxic T-cell infiltration and the efficacy of immune therapies. Here, we present a novel strategy harnessing acute transplant rejection mechanisms by employing a recombinant oncolytic rVMG vector engineered to express the murine H-2Kk MHC class I alloantigen (rVMG-H-2Kk), thereby inducing tumor-specific antigenic mismatch responses. In vitro, rVMG-H-2Kk exhibited strong replication and cytolytic activity while inducing cell surface expression of both H-2Kk and endogenous H-2Kb, in addition to upregulation of antigen presentation genes ({beta}2-microglobulin, Tap1, and Tapbp). In two independent immunocompetent PDAC models, intratumoral and systemic delivery of rVMG-H-2Kk delayed tumor progression and prolonged survival. Multiplex immunohistochemistry and immunophenotyping revealed substantial TME remodeling, marked by increased effector T-cell infiltration, regulatory T-cell depletion, and reduced fibrosis. Spatial transcriptomics further showed compartment-specific immune activation and epithelial metabolic reprogramming, corroborating with enhanced tumor immunogenicity. Despite these effects, rVMG-H-2Kk also induced compensatory immunosuppressive pathways, including upregulation of antiviral response genes and immune checkpoint receptors such as PDL-2. Importantly, combination therapy with rVMG-H-2Kk and murine checkpoint blockade (anti-PD-1 and anti-CTLA-4) drastically improved survival than checkpoint blockade alone. Strikingly, surviving mice resisted tumor rechallenge, indicating the establishment of durable antitumor memory. Collectively, these findings establish rVMG-H-2Kk as a novel immunotherapeutic platform capable of converting immune-cold tumors into immune-hot, sensitizing tumors to immune checkpoint inhibitors, and establishing durable antitumor immunity in PDAC. One Sentence SummaryOncolytic virus-based delivery of an alloantigen improves antitumor immunity and synergizes with immune checkpoint inhibitors in pancreatic cancer. Significance statementDelivery of murine alloantigens via an engineered oncolytic vesiculovirus, combined with immune checkpoint blockade, overcomes immunosuppressive barriers and establishes durable antitumor immunity in PDAC.

cancer biology↗

bioRxiv2022

In vivo Safety and Immunoactivity of Oncolytic Jurona Virus in Hepatocellular Carcinoma: A Comprehensive Proteogenomic Analysis

Oncolytic viruses can effectively unwrap a multimodal anti-tumor activity, encompassing a selective tumor cell killing and promoting a systemic anti-tumor immunity, making them a formidable foe against cancer. Among these, several members of the Rhabdoviridae family are particularly attractive as oncolytic agents due to their natural tumor selectivity and non-pathogenicity in humans. In this study, we demonstrated that intratumorally (IT) administration of Jurona virus (JURV), a novel oncolytic Rhabdovirus, induces dynamic tumor regression in human HCC xenograft and syngeneic models. Our data shows that IT injections of JURV trigger the recruitment and activation of cytotoxic T (CTLs) and decrease the tumor-associated macrophages (TAM) infiltration leading to tumor growth delay in both local and distant murine HCC tumors in a syngeneic model. Moreover, when administered concomitantly, JURV and anti-PD-1 therapy profoundly modulate the tumor microenvironment (TME) via enhanced infiltration of CTLs, suggesting that immune checkpoint blockade therapy could potentiate the immunomodulatory effect of JURV and potentially provide durable anti-tumor immunity. Our analysis of the molecular and cellular mechanism of JURV-medicated anti-cancer activity unveiled that JURV and anti-PD-1 antibodies activate different effectors of the immune system but have complementary anti-tumor activities. Furthermore, our results indicate that the abscopal effect induced by JURV is likely mediated by the mechanism regulating the T helper cell responses. Our work supports the further development of JURV as a novel immunovirotherapy platform for hepatocellular carcinoma.

immunology↗

bioRxiv2022

Characterization of Morreton Virus (MORV) as a Novel Oncolytic Virotherapy Platform for Liver Cancers

Morreton virus (MORV) is a novel oncolytic Vesiculovirus, genetically distinct from vesicular stomatitis virus (VSV). we report that MORV induced potent cytopathic effects in a panel of cholangiocarcinoma (CCA) and hepatocellular carcinoma (HCC) cell lines. In addition, high intranasal doses of MORV were not associated with significant adverse effects and were well tolerated in mice bearing liver tumor xenografts and syngeneic liver cancers. Furthermore, single intratumoral treatments with MORV (1 x 107 TCID50) triggered a robust antitumor immune response leading to substantial tumor regression and disease control in a syngeneic CCA model, using 10-fold lower dose compared to VSV (1 x 108 TCID50). In addition, MORV and VSV both induced prominent tumor growth delay in immunodeficient mice bearing Hep3B hepatocellular carcinoma (HCC) but not in mice bearing HuCCT-1 CCA xenografts. Our findings indicate that wild-type MORV is safe and can induce potent tumor regression in HCC and CCA animal models without adverse events via immune-mediated and immune-independent mechanisms. Further development and clinical translation of MORV as virotherapy for liver cancers are warranted.

immunology↗

bioRxiv2022

Repurposing Live Attenuated Trivalent MMR Vaccine as Cost-effective Cancer Immunotherapy

Despite its rising promise, cancer immunotherapy remains out of reach for many patients because of the extensive cost of manufacturing immunotherapy products. In this study, we show that intratumoral injections of the trivalent measles, mumps, and rubella (MMR) live attenuated viral vaccine (LAVs) modulates a potent cytotoxic T-cell antitumor immune response, resulting in tumor growth inhibition and improved survival in syngeneic mouse models of hepatocellular carcinoma and colorectal cancer. Using an integrated transcriptomic and proteomic approach, we demonstrated that mechanistically, MMR exerts its antitumor activity by priming innate and adaptive antitumor immune responses, leading to immunologically coordinated cancer cells death. Our findings highlight a promising potential for LAVs, such as MMR, to be repurposed as cost-effective cancer immunotherapy.

immunology↗

bioRxiv2020

Making WAVES in Breedbase: An Integrated Spectral Data Storage and Analysis Pipeline for Plant Breeding Programs

Visible and near-infrared (vis-NIRS) spectroscopy is a promising tool for increasing phenotyping throughput in plant breeding programs, but existing analysis software packages are not optimized for a breeding context. Additionally, commercial software options are often outside of budget constraints for some breeding and research programs. To that end, we developed an open-source R package, waves, for the streamlined analysis of spectral data with several cross-validation schemes to assess prediction accuracy. Waves is compatible with a wide range of spectrometer models and performs visualization, filtering, aggregation, cross-validation set formation, model training, and prediction functions for the association of vis-NIRS spectra with reference measurements. Furthermore, we have integrated this package into the Breedbase family of open-source databases, expanding the analysis capabilities of this growing digital ecosystem to a number of crop species. Taken together, the standalone and Breedbase versions of waves enhance the accessibility of tools for the analysis of spectral data during the plant breeding process. Core ideasO_LIwaves is an open-source R package for spectral data analysis in plant breeding C_LIO_LIBreeding relevant cross-validation schemes to evaluate predictive accuracy of models C_LIO_LIExtension of Breedbase--an open-source database--to support spectral data storage C_LIO_LIGraphical user interface developed for implementation of waves in Breedbase C_LI

bioinformatics↗