Biology subjects

Reis, E. M.

Publications and source records attributed to Reis, E. M..

4 recordsLinked to original sources

bioRxiv2026

Subtype-Resolved Pain-Signaling Architectures Reveal Conserved Drug-Target Interaction Networks in DRG Nociceptors

Pain management has been challenging and a major obstacle lies in the limited translational success between preclinical studies, often based on rodent models and evoked nociception behavioral assays, whose validity is often questioned. The dorsal root ganglia (DRG) contains diverse nociceptor subtypes that serve as the primary afferent pathways for detecting painful stimuli and analgesics often target proteins expressed in nociceptors. This makes the distinct protein repertoires and molecular interactors within nociceptor subtypes a key focus for understanding which molecular players drive pain processing and how they may be therapeutically targeted. The confirmation of cross-species conservation of pain-related signaling pathways, mediated by nociceptors, could help to elucidate the molecular mechanisms by which the drugs act across species. In this context, we constructed and compared experimentally-validated protein-protein interaction (PPI) networks based on drug targets and their direct binding partners for nociceptor subtypes supported by single-nuclei transcriptome data from mouse and human DRGs. We found that overall gene expression is more conserved across mice than in human nociceptor subtypes, indicating a higher degree of molecular specialization of human nociceptors. Overall signaling network analyses revealed subtype- and species-specific conservation related to pain signaling, with some particularities, in which key drug targets mediate broader cellular processes beyond pain signaling and neuronal depolarization. Altogether, this resource may help to further understand the molecular mechanisms of specific drug targeting, and the proposed workflow can be used to identify and prioritize pain-related pathways in the DRG, advancing target identification and translational medicine.

cell biology↗

bioRxiv2026

Reduced levels of inositol hexakisphosphate kinase (IP6K) impair life-cycle transitions and the intracellular development of Trypanosoma cruzi within human cardiomyocytes

Trypanosoma cruzi is the etiological agent of Chagas disease. During its life cycle, T. cruzi undergoes several key differentiation processes that are essential for its survival. The precise mechanisms that regulate these processes remain elusive, and any interference in this cycle would represent a breakthrough in the development of effective therapy against Chagas disease. Here, after depleting a single IP6K allele of T. cruzi, we observed that key differentiation processes (metacyclogenesis, amastigogenesis and trypomastigogenesis) were profoundly impaired. Epimastigote forms of IP6K-deficient T. cruzi exhibited morphological alterations and reduced metacyclogenesis. IP6K-deficient metacyclic forms had reduced infective potential in human cardiomyocytes. IP6K-deficient amastigote forms showed impaired ability to transform into trypomastigotes, with most of the population egressing from human cardiomyocytes without completing trypomastigogenesis. Together, our results suggest that IP6K is critical to sustain the T. cruzi life cycle. Since disruption of both IP6K alleles was lethal and the primary structure of IP6K shares only [~]25% similarity with its human homolog, this kinase emerges as a promising target for drug development against Chagas disease. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=153 HEIGHT=200 SRC="FIGDIR/small/700787v2_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@1cb37f0org.highwire.dtl.DTLVardef@c59fb8org.highwire.dtl.DTLVardef@791cb7org.highwire.dtl.DTLVardef@14c68fd_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2025

LncRNA LINC00941 Links Oncogenic KRAS Signaling to Aggressiveness and Chemoresistance in Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers, driven largely by oncogenic KRAS, yet effective targeted therapies remain unavailable. Long noncoding RNAs (lncRNAs) are emerging as key regulators of tumor biology, but their role in KRAS-driven PDAC is not well defined. To address this gap, we integrated RNA sequencing, exome, and clinical data from The Cancer Genome Atlas (TCGA) and identified 49 long intergenic noncoding RNAs (lincRNAs) differentially expressed according to KRAS status. Among the ten most abundant, LINC00941 and AC006262.5 showed the strongest differential expression in an independent PDAC cohort from the International Cancer Genome Consortium (ICGC). Experimental validation in KRAS-mutant PDAC cell lines and isogenic pancreatic epithelial models confirmed KRAS-dependent regulation of LINC00941, which was consistently upregulated in patient tumors and correlated with poor prognosis in both TCGA and ICGC datasets. Single-cell transcriptomic analysis further demonstrated that LINC00941 is enriched in malignant epithelial populations. Functional assays revealed that LINC00941 silencing impaired migration and invasion, reduced DNA repair capacity, and sensitized PDAC cells to gemcitabine, while having little effect on viability. Supporting these findings, co-expression and enrichment analyses linked LINC00941 to pathways regulating cell adhesion, motility, extracellular matrix organization, and DNA repair. Together, these findings demonstrate that oncogenic KRAS reshapes the lncRNA landscape in PDAC and identify LINC00941 as a KRAS-regulated oncogenic lncRNA that promotes aggressiveness and chemoresistance, highlighting its prognostic value and potential as a therapeutic target.

cancer biology↗

bioRxiv2022

Gene amplification mutations originate prior to selective stress in Acinetobacter baylyi

The controversial theory of adaptive amplification states gene amplification mutations are induced by selective environments where they are enriched due to the stress caused by growth restriction on unadapted cells. We tested this theory with three independent assays using an Acinetobacter baylyi model system that exclusively selects for cat gene amplification mutants. Our results demonstrate all cat gene amplification mutant colonies arise through a multistep process. While the late steps occur during selection exposure, these mutants derive from low-level amplification mutant cells that form before growth-inhibiting selection is imposed. During selection, these partial mutants undergo multiple secondary steps generating higher amplification over several days to multiple weeks to eventually form visible high-copy amplification colonies. Based on these findings, amplification in this Acinetobacter system can be explained by a natural selection process that does not require a stress response. These findings have fundamental implications to understanding the role of growth-limiting selective environments on cancer development.

genetics↗