Biology subjects

Bautista, D.

Publications and source records attributed to Bautista, D..

4 recordsLinked to original sources

bioRxiv2026

Epigenetic evolution of colorectal cancer and its microenvironment reveals new vulnerabilities

Epigenetics is central to tumorigenesis, but the co-evolution of the cancer epigenome and its microenvironment is severely understudied. Here, we measure chromatin accessibility and transcriptome, at single cell resolution, of a set of normal colon, primary colorectal cancers and metastases, and identify recurrent epigenetic alterations in tumour cells. We also found that the normal epithelium adjacent to the cancer had recurrent epigenetic alterations associated with inflammatory programs that were partially shared with tumour cells. Distinct tumour-intrinsic transcription factor binding programs were associated with differential abundance of malignant stroma cell identities. We then leveraged matched patient-derived organoids, to assess the functional impact of the most recurrent epigenetic alterations on cancer cell viability, using CRISPR interference. We found a set of epigenetic-driven cancer dependencies, related to developmental reprogramming and cellular stress resilience, representing new potential therapeutic targets.

cancer biology↗

bioRxiv2026

Bexobrutideg: A Selective, Catalytic Degrader of Bruton's Tyrosine Kinase Overcomes Inhibitor Resistance and Suppresses Autoantibody-Mediated Disease

Brutons tyrosine kinase (BTK) transduces B-cell receptor (BCR), Toll-like receptor (TLR), and Fc receptor (FcR) signaling, and overactivation of these pathways drives B-cell malignancies and antibody-mediated autoimmune disease. Small molecule inhibitors block the enzymatic functions of BTK, but this inhibition is undermined by resistance mutations, several of which abolish BTKs kinase activity yet promote oncogenic signaling through BTK scaffolding functions. We report the discovery and characterization of bexobrutideg (NX-5948), a heterobifunctional degrader that recruits cereblon (CRBN) to selectively degrade BTK while sparing molecular glue neosubstrates. We demonstrate that bexobrutideg acts catalytically, degrading thousands of copies of BTK per molecule per hour, and this event-driven pharmacology renders it resilient to mutations that confer resistance to both covalent- and noncovalent-inhibitors. Bexobrutideg is orally bioavailable, driving deep and durable BTK degradation across species. Bexobrutideg demonstrates strong efficacy in wild-type and ibrutinib-resistant lymphoma models and robustly suppresses pathway activation in models of autoimmune disease.

cancer biology↗

bioRxiv2026

A Drosophila screen identifies domino as a link between chromatin regulation and synaptic organization

While heterozygous gene-disrupting variants in dosage-sensitive genes are strongly implicated in autism spectrum disorder (ASD), their effects on behavior in vivo remain poorly understood. To address this, we conducted a targeted behavioral screen in Drosophila using high-confidence ASD risk genes. This screen identified 48 lines with altered sleep, activity, or social behavior, including many genes not previously known to regulate these behaviors. The chromatin remodeler domino (dom) emerged as a compelling hit. Heterozygous mutants showed altered social spacing and male-biased changes in sleep and activity. RNA-sequencing revealed changes in gene expression and splicing associated with synaptic pathways. Consistent with these molecular changes, immunofluorescence revealed increased presynaptic activity in a brain region associated with sleep and sensory processing. Together, these findings show that partial loss of ASD risk genes is sufficient to alter behavior and identify dom as a link between transcriptional regulation, synaptic organization and behavior.

neuroscience↗

bioRxiv2025

Microscopical and molecular characterization of the infection cycle of Phytophthora betacei during disease development on tree tomato (Solanum betaceum).

Phytophthora betacei is a recently described oomycete plant pathogen closely related to Phytophthora infestans sensu stricto. This plant pathogen naturally infects tree tomato (Solanum betaceum) but has not been reported on tomatoes and potatoes, the primary hosts of P. infestans. The aim of this study was to characterize the infection cycle of P. betacei using microscopy and molecular approaches. Several strains were inoculated in susceptible tree tomato plants and disease progression was monitored via six epidemiological parameters. Although different P. betacei strains displayed a highly variable disease phenotype, the most aggressive one was chosen for further plant inoculations. Samples at different time points of the infection cycle were analyzed at the cellular level via light and scanning electron microscopy (SEM) and at the molecular level via qRT-PCR of infection-stage-specific markers. The infection cycle of P. betacei differed from that of P. infestans in having a longer biotrophic stage, larger lesions, and higher sporulation capacity. Additionally, P. betacei transcriptomic profiles were monitored along the infection cycle via RNAseq and evidenced a changing expression landscape that supports an elongated hemibiotrophic transition and a clear distinction from what is being expressed in the mycelium or the sporangia. This study provides novel insights into the interaction between P. betacei and S. betaceum.

plant biology↗