Biology subjects

Gallegos, D.

Publications and source records attributed to Gallegos, D..

5 recordsLinked to original sources

bioRxiv2026

Structural Analysis of Prostate Cancer N-Glycans Using Graph-Based Structural Metrics

The N-linked glycans are structurally complex carbohydrate modifications that regulate protein folding, immune recognition, and cellular signaling, and their expression is extensively remodeled during cancer progression, making them promising biomarkers. In this study, prostate cancer-associated N-glycans from a range of relevant peer-reviewed studies were curated and digitized to develop a versatile computational framework that quantitatively encodes their spatial complexity across diverse biological systems. We invented two indices--the Distance & Connectivity Index (DCI) and the Position & Composition Index (PCI)--to capture the spatial information in N-glycans as layered architectures, enabling calculation of residue-level path lengths, branching structure, and compositional diversity. DCI summarizes glycan structure as both a scalar and matrix representation, while PCI does the same but also captures monosaccharide diversity, linkage heterogeneity, and cross-layer branching features. These metrics were computed with GlycoAssessor, an open-source platform that extracts information for the DCI and PCI from glycans drawn via Symbol Nomenclature for Glycans (SNFG) notation. Principal Component Analysis (PCA) was applied to evaluate whether glycans from prostate cancer tissues cluster distinctly in a disease-relevant manner. Results show that the spatial information in N-glycans: (1) increased in a multi-dimensional, non-linear manner, (2) objectively segregated structural themes, (3) could function as a potential prostate cancer biomarker that is distinct from mass-to-charge ratio and relative abundance, and (4) could objectively quantify novel subtype classifications of glycans associated with disease states and progression.

bioinformatics↗

bioRxiv2025

Mutant p53 binds RNA to drive mitochondrial dysfunction

Tumor suppressor protein 53 (p53) is a transcription factor that is deregulated in 50% of cancers. Often termed the guardian of the genome, p53 is responsible for maintenance of genomic stability, cell cycle arrest, DNA repair, senescence, and apoptosis. In cancer cells, deregulation of p53 often occurs through mutations in the DNA binding domain which lead to a loss of the transcriptional activity. While 100s of somatic mutations in the DNA binding domain are known, a small number of mutants are enriched in cancer, suggesting a gain-of-function role. Here we deploy an intein-based approach to localize {micro}Map photoproximity labeling to p53 to define novel interactions contributing to the loss and gain of function roles of 5 separate hotspot mutants. These data revealed that G245S and R273H binds to RNA through its C-terminal domain. We show through CLIP experiments that mutant p53 has an RNA binding motif that conserved across mutants and is enriched in 3UTRs, promoting ribosomal localization and labeling of proteins at the mitochondrial surface. We further demonstrate that the RNA binding ability of mutant p53 promotes altered miRNA processing and mitochondrial dysfunction providing mechanistic rationale for historically reported but poorly understood phenotypes.

molecular biology↗

bioRxiv2025

Decoding Cellular Stress States for Toxicology Using Single-Cell Transcriptomics

We applied the TempO-LINC(R) platform to generate single-cell transcriptomic (SCTr) profiles of [~]40,000 HepaRG cells exposed to etoposide, brefeldin A, cycloheximide, rotenone, tBHQ, troglitazone, and tunicamycin at three concentrations for 24 hours. SCTr enabled a detailed analysis of adaptive stress response pathways (SRPs), including the unfolded protein response (UPR), oxidative stress response (OSR), heat shock response (HSR), and DNA damage response (DDR). Troglitazone upregulated lipid metabolism genes (PLIN2, ACOX1) along with HSR and UPR activation, with co-expression of DNAJA1, HSP90AA1, and DDIT3 in subsets of cells. Brefeldin A and tunicamycin strongly induced UPR markers (HSPA5, SYVN1, LMF2, PDIA4) in subsets of cells, with some also expressing apoptotic (DDIT3, CASP8) and autophagic (SQSTM1) genes, indicating diverse stress responses. Rotenone activated GDF15, TRIB3, and DDIT3 in a fraction of cells, accompanied by PLIN2 and mild UPR induction, reflecting heterogeneous mitochondrial stress responses. We scored individual cells using literature-derived SRP gene signatures to characterize overall stress phenotypes and clustered them using a generalized Jaccard metric. The clustering revealed five phenotypic groups spanning cell states associated with homeostasis, adaptive responses, terminal outcomes, autophagy, and apoptosis. By systematically analyzing the distributions of cells in different states across treatments, we visualized dynamic shifts in cellular subpopulations responding to chemicals, revealing early stress responses and potential transitions to cell death. Our findings suggest the utility of SCTr in decoding stress states that could provide possible insights into transitions between cellular adaptive and terminal transitions involved in toxicity.

pharmacology and toxicology↗

bioRxiv2021

Mitophagy antagonism by Zika virus reveals Ajuba as a regulator of PINK1-Parkin signaling, PKR-dependent inflammation, and viral invasion of tissues.

Dysregulated inflammation dominated by chemokine expression is a key feature of disease following infection with the globally important human pathogens, Zika virus (ZIKV) and dengue virus, but a mechanistic understanding of how pro-inflammatory responses are initiated is lacking. Mitophagy is a quality control mechanism that regulates innate immune signaling and cytokine production through selective degradation of damaged mitochondria. Here, we demonstrate that ZIKV NS5 antagonizes mitophagy by binding to the host protein Ajuba and preventing its translocation to depolarized mitochondria where it is required for PINK1 activation and downstream signaling. Consequent mitophagy suppression amplified the production of pro-inflammatory chemokines through PKR sensing of mitochondrial RNA. In Ajuba-/- mice, ZIKV induced early expression of pro-inflammatory chemokines associated with significantly enhanced dissemination to tissues. This work identifies Ajuba as a critical regulator of mitophagy, and demonstrates a role for mitophagy in limiting systemic inflammation following infection by globally important human viruses.

microbiology↗

bioRxiv2018

A Striatal interneuron circuit for continuous target pursuit

Most adaptive behaviors require precise tracking of targets in space. In pursuit behavior with a moving target, mice use distance to target to guide their own movement continuously. Here we show that in the sensorimotor striatum, parvalbumin-positive fast-spiking interneurons (FSIs) can represent the distance between self and target during pursuit behavior, while striatal projection neurons (SPNs), which receive FSI projections, can represent self-velocity. FSIs are shown to regulate velocity-related SPN activity during pursuit, so that movement velocity is continuously modulated by distance to target. Moreover, bidirectional manipulation of FSI activity can selectively disrupt performance by increasing or decreasing the self-target distance. Our results reveal a key role of the FSI-SPN interneuron circuit in pursuit behavior, and elucidate how this circuit implements distance to velocity transformation required for the critical underlying computation.

neuroscience↗