Biomedical subjects

Juan He

Publications and source records attributed to Juan He.

4 recordsLinked to original sources

PubMed2026

A chromosome-level genome assembly of Lycoris radiata reveals the evolutionary origin of Amaryllidaceae alkaloids and elucidates the complete galanthamine biosynthetic pathway.

Amaryllidaceae alkaloids (AmAs) comprise a structurally diverse group of specialized metabolites produced almost exclusively by species of the Amaryllidoideae subfamily and are of substantial pharmacological importance. However, the limited availability of high-quality genomes from Amaryllidoideae plants has constrained systematic investigations of the genes and evolutionary processes underlying AmA biosynthesis. Here, we present a chromosome-level genome assembly of Lycoris radiata, which enabled the discovery of key downstream enzymes in the galanthamine biosynthetic pathway and uncovered reversible reactions between two critical metabolite pairs. These findings provide new mechanistic insight into pathway architecture and enable reconstruction of the galanthamine biosynthetic pathway in Yarrowia lipolytica. Comparative genomic analyses indicate that several core genes for AmA biosynthesis originated in ancestral angiosperms, whereas the complete pathway was likely assembled in the Amaryllidoideae subfamily through gene duplication and neofunctionalization. Furthermore, integrated metabolomic and transcriptomic analyses suggest that roots contribute actively to AmA metabolism in Lycoris. Together, these findings provide a genomic and biochemical framework for understanding the evolution and engineering of AmA biosynthesis.

Lycoris↗

PubMed2025

A pancreatic cancer organoid biobank links multi-omics signatures to therapeutic response and clinical evaluation of statin combination therapy.

Chemotherapy remains the primary treatment for pancreatic ductal adenocarcinoma (PDAC), but most patients ultimately develop resistance. Here, we established 260 pancreatic cancer organoid lines, followed by extensive multi-omics profiling and therapeutic sensitivity assessments. Integrated analyses uncovered 6 novel coding and 35 noncoding driver candidates. We discovered 2,794 multi-omics features associated with drug sensitivity and 322 features linked to radiation sensitivity. Pharmacogenomic analyses revealed that chemoresistant organoids exhibited enrichment in protein glycosylation and cholesterol metabolism pathways. Notably, statins effectively targeted chemoresistant PDAC organoids. Statin treatment attenuated protein glycosylation, cholesterol levels, and the epithelial-to-mesenchymal transition (EMT) signature in PDAC organoids. We conducted a single-center, single-arm, phase 2 clinical trial (NCT06241352) combining atorvastatin with chemotherapy in patients with advanced pancreatic cancer. Among 37 patients, 26 (70.3%) demonstrated a response, with tumor markers decreasing by more than 20%, suggesting durable responses and potential clinical benefits in this challenging patient population.

Humans↗

PubMed2025

The Tartary Buckwheat FtMYB46-FtNRAMP3 Module Enhances Plant Lead and Cadmium Tolerance.

The presence of toxic heavy metals lead (Pb) and cadmium (Cd) in polluted soil damage crop production and consequently harms human and livestock health. Tartary buckwheat (Fagopyrum tataricum) is a potential model plant for heavy metal phytoremediation because of its valuable characteristics of high heavy metal tolerance and abundant biomass production. Here, we report that the Tartary buckwheat FtMYB46-FtNRAMP3 module enhances plant Pb and Cd tolerance. RNA sequencing analysis showed that Pb treatment specifically induced expression of FtNRAMP3, a member of the NRAMP (Natural Resistance-Associated Macrophage Protein) transporter gene family. Further cytological and biochemical analysis revealed that FtNRAMP3 was localised to the plasma membrane and significantly contributed to increased tolerance to Pb and Cd in yeast cells. Consistently, transgenic overexpression of FtNRAMP3 in Arabidopsis significantly increased plant tolerance to Pb and Cd applications, reducing Pb concentration but increasing Cd concentration in the overexpression transgenic plants. Subsequent yeast one-hybrid and electrophoretic mobility shift assays showed that the transcription factor FtMYB46 directly binds to the FtNRAMP3 promoter. Further, FtMYB46 promoted FtNRAMP3 expression and increased plant Pb and Cd tolerance. Overall, this study demonstrates the important role of the FtMYB46-FtNRAMP3 module and its potential value in the phytoremediation of Pb and Cd stress.

Cadmium↗

PubMed2025

LKB1 inactivation promotes epigenetic remodeling-induced lineage plasticity and antiandrogen resistance in prostate cancer.

Epigenetic regulation profoundly influences the fate of cancer cells and their capacity to switch between lineages by modulating essential gene expression, thereby shaping tumor heterogeneity and therapy response. In castration-resistant prostate cancer (CRPC), the intricacies behind androgen receptor (AR)-independent lineage plasticity remain unclear, leading to a scarcity of effective clinical treatments. Utilizing single-cell RNA sequencing on both human and mouse prostate cancer samples, combined with whole-genome bisulfite sequencing and multiple genetically engineered mouse models, we investigated the molecular mechanism of AR-independent lineage plasticity and uncovered a potential therapeutic strategy. Single-cell transcriptomic profiling of human prostate cancers, both pre- and post-androgen deprivation therapy, revealed an association between liver kinase B1 (LKB1) pathway inactivation and AR independence. LKB1 inactivation led to AR-independent lineage plasticity and global DNA hypomethylation during prostate cancer progression. Importantly, the pharmacological inhibition of TET enzymes and supplementation with S-adenosyl methionine were found to effectively suppress AR-independent prostate cancer growth. These insights shed light on the mechanism driving AR-independent lineage plasticity and propose a potential therapeutic strategy by targeting DNA hypomethylation in AR-independent CRPC.

Male↗