Biology subjects

Saavedra, B.

Publications and source records attributed to Saavedra, B..

4 recordsLinked to original sources

bioRxiv2025

Development of iPSC-Derived T Cells Targeting EGFR Neoantigens in Non-Small Cell Lung Cancer

A long-sought goal of cancer immunotherapy is to mass-produce T cells that specifically target tumor neoantigens. One decisive challenge is the identification of neoantigens derived from cancer driver genes. Here, we identify T cells that recognize the NSCLC-associated EGFR C797S mutation, which confers resistance to current inhibitors and is linked to poor prognosis. To overcome limitations in T cell availability, we reprogrammed EGFR C797S-specific T cells into induced pluripotent stem cells (iPSCs) and re-differentiated them into CD8 T cells. These iPSC-derived T cells specifically recognized the EGFR C797S mutation and effectively killed cancer cells expressing this mutation. Our findings underscore the potential of targeting driver mutation-derived neoantigens for immunotherapy and demonstrate that iPSC-derived T cells can mediate antitumor effects. Collectively, this approach combining neoantigen identification with T cell reprogramming may offer a promising strategy for targeting drug-resistant tumors.

immunology↗

bioRxiv2024

Aniline Dioxygenase in Rhodococcus ruber R1: Insights into Skatole Degradation

Skatole is an aromatic heterocyclic compound with a strong offensive odor, produced by microorganisms during the anaerobic breakdown of tryptophan. Skatole accumulation is linked to environmental and health issues. Despite its persistence and harmful effects, skatoles biodegradation by microorganisms is poorly understood. We have recently isolated a gram-positive bacterium, Rhodococcus ruber R1, which uses skatole as its sole carbon and energy source. Here we report an operon consisting of 14 genes encoding aromatic oxygenase systems involved in skatole degradation in Rhodococcus ruber R1. Cells growing on skatole accumulate aniline transiently, indicating its role as an intermediate in the degradation pathway. We characterize six genes in this cluster that encode for an aniline dioxygenase, which converts aniline to catechol and is only activated in the presence of skatole. This gene cluster was successfully introduced into a heterologous strain enabling the full degradation of aniline and its derivatives. Phylogenetic analysis of aniline dioxygenase present in R1 strain reveals a widespread distribution of this system among bacteria, in contrast to the full skatole cluster, which is restricted to a few genera. These findings advance our understanding of the skatole degradation pathway and highlight R1s potential for bioremediation of skatole, aniline, and related contaminants.

microbiology↗

bioRxiv2023

Exposure to constant artificial light alters honey bee sleep rhythms and disrupts sleep

Artificial light at night (ALAN) is known to create changes in animal behavior in some invertebrates and vertebrates and can result in decreased fitness. ALAN effects have not been studied in European honey bees (Apis mellifera), an important pollinator. Colonies can be exposed to ALAN in swarm clusters, when bees cluster outside the nest on hot days and evenings, and, in limited cases, when they build nests in the open. Forager bees maintained in incubated cages were subjected to constant light or dark and observed with infrared cameras. The bees maintained a regular sleep pattern for three days but showed a shift on the fourth day in the presence of continuous light. Bees under constant light demonstrated a 24.05-hour rhythm, compared to a 23.12-hour rhythm in the dark. After 95 hours, the light-exposed bees slept significantly less and experienced significantly more disturbances from their peers. They also preferred to sleep in the lower portion of the cages, which had lower light intensity. These findings suggest that ALAN can disrupt honey bees sleep patterns, which may have implications for their behavior and overall colony health.

animal behavior and cognition↗

bioRxiv2021

Controlling homology-directed repair outcomes in human stem cells with dCas9

Modeling human disease in human stem cells requires precise, scarless editing of single nucleotide variants (SNV) on one or both chromosomes. Here we describe improved conditions for Cas9 RNP editing of SNVs that yield high rates of biallelic homology-directed repair. To recover both heterozygous and homozygous SNV clones, catalytically inactive dCas9was added to moderate high activity Cas9 RNPs. dCas9 can also block re-cutting and damage to SNV alleles engineered with non-overlapping guide RNAs.

genetics↗