Biology subjects

Reyes, T.

Publications and source records attributed to Reyes, T..

3 recordsLinked to original sources

bioRxiv2025

KLF4 promotes a KRT13+ hillock-like state in squamous lung cancer

Lung squamous cell carcinoma (LUSC) is a basal-like subtype of lung cancer with limited treatment options. While prior studies have identified tumour-propagating cell states in squamous tumours, the broader landscape of intra-tumoural heterogeneity within LUSC remains poorly understood. Here, we employ Sox2-driven mouse models, organoid cultures, and single-cell transcriptomic analyses to uncover previously unrecognized levels of cell fate diversity within LUSC. Specifically, we identify a KRT13+ hillock-like population of slower-dividing tumour cells characterized by immunomodulatory gene expression signatures. The tumour hillock-like state is conserved across multiple animal and human-derived models and is present in the majority of human LUSCs as well as head and neck and esophageal squamous tumours. Our findings shed light on the cellular origins of tumour hillock-like states: lung club cells give rise to tumours with luminal hillock-like populations, while basal-like tumour-propagating cells transition into basal hillock-like states, resembling lineage plasticity trajectories of the normal lung. Mechanistically, KLF4 promotes KRT13, a broadly conserved hillock-like state with enrichment of potential therapeutic targets, and resistance to platinum-based chemotherapy. Together, these results provide molecular insights into the lineage plasticity underlying intra-tumoural heterogeneity within LUSC, offering potential avenues for new therapeutic strategies.

cancer biology↗

bioRxiv2024

Design of Novel Dehalogenases using Protein Large Language Models

Per- and polyfluoroalkyl substances (PFAS) are toxic compounds linked to cancers, infertility, and vaccine resistance at concentrations above 1 part per trillion. Owing to strong carbon-fluorine bonds, they are persistent in the environment, taking centuries to millennia to degrade. As part of the 2024 iGEM competition, several high school students local to the Pasadena area leveraged recently-developed bioinformatic tools and large language models to discover and design novel reductive dehalogenases predicted to degrade perfluorooctanoic acid (PFOA), a long chain PFAS whose manufacture is prohibited, yet still persists in the environment and drinking water. The team identified 68 enzymes with structural similarity to Acidimicrobium sp. Strain A6 RdhA, the only specific known PFAS degrading enzyme in nature, expressed and refolded 5 of these enzymes in addition to 1 rational, and 3 large language model designs. These designs all have diverse sequences yet all are predicted to retain key substrate and cofactor binding pockets. These enzymes will be assayed on the ability to defluorinate PFOA.

bioengineering↗

bioRxiv2024

Global genomics of Aedes aegypti unveils widespread and novel persistent infectious viruses capable of triggering a small RNA response

The mosquito Aedes aegypti is a prominent vector for arboviruses, but the breadth of mosquito viruses that infects this specie is not fully understood. In the broadest global survey to date of over 200 Ae. aegypti small RNA samples, we detected viral small interfering RNAs (siRNAs) and Piwi interacting RNAs (piRNAs) arising from mosquito viruses. We confirmed that most academic laboratory colonies of Ae. aegypti lack persisting viruses, yet two commercial strains were infected by a novel tombus-like virus. Ae. aegypti from North to South American locations were also teeming with multiple insect viruses, with Anphevirus and a bunyavirus displaying geographical boundaries from the viral small RNA patterns. Asian Ae. aegypti small RNA patterns indicate infections by similar mosquito viruses from the Americas and reveal the first wild example of dengue virus infection generating viral small RNAs. African Ae. aegypti also contained various viral small RNAs including novel viruses only found in these African substrains. Intriguingly, viral long RNA patterns can differ from small RNA patterns, indicative of viral transcripts evading the mosquitoes RNA interference (RNAi) machinery. To determine whether the viruses we discovered via small RNA sequencing were replicating and transmissible, we infected C6/36 and Aag2 cells with Ae. aegypti homogenates. Through blind passaging, we generated cell lines stably infected by these mosquito viruses which then generated abundant viral siRNAs and piRNAs that resemble the native mosquito viral small RNA patterns. This mosquito small RNA genomics approach augments surveillance approaches for emerging infectious diseases.

genomics↗