Identification of modulators of the ALT pathway through a native FISH-based optical screen.

A significant portion of human cancers utilize a recombination-based pathway, alternative lengthening of telomeres (ALT), to extend telomeres. To gain further insights into this pathway, we developed a high-throughput imaging-based screen named TAILS (telomeric ALT in situ localization screen) to identify genes that either promote or inhibit ALT activity. Screening over 1,000 genes implicated in DNA transactions, TAILS reveals both well-established and putative ALT modulators.

The central role of creatine and polyamines in fetal growth restriction.

Placental insufficiency often correlates with fetal growth restriction (FGR), a condition that has both short- and long-term effects on the health of the newborn. In our study, we analyzed placental tissue from infants with FGR and from infants classified as small for gestational age (SGA) or appropriate for gestational age (AGA), performing comprehensive analyses that included transcriptomics and metabolomics. By examining villus tissue biopsies and 3D trophoblast organoids, we identified significant metabolic changes in placentas associated with FGR.

Identification of Novel Modulators of the ALT Pathway Through a Native FISH-Based Optical Screen.

A significant portion of human cancers utilize a recombination-based pathway, Alternative Lengthening of Telomeres (ALT), to extend telomeres. To gain further insights into this pathway, we developed a high-throughput imaging-based screen named TAILS (Telomeric ALT Localization Screen), to identify genes that either promote or inhibit ALT activity. Screening over 1000 genes implicated in DNA transactions, TAILS revealed both well-established and novel ALT modulators.

Suppression of the - axis shifts arginine into the phosphocreatine energy system in pancreatic cancer cells.

In pancreatic ductal adenocarcinomas (PDAC), the axis controls cellular functions such as redox homeostasis and metabolism. Disruption of this axis through suppression of leads to profound reprogramming of metabolism. Unbiased transcriptome and metabolome analyses showed that PDAC cells with disrupted signaling ( cells) shift from aerobic glycolysis to metabolic pathways fed by amino acids.

NRF2 interacts with distal enhancer and inhibits nitric oxide synthase 2 expression in KRAS-driven pancreatic cancer cells.

Nitric oxide is a pleiotropic free radical produced by three nitric oxide synthases (NOS1-3), of which inducible NOS2 is involved in tumor initiation and progression. In this study, RNA-seq, ChIP-seq and qRT-PCR experiments combined with bioinformatic analyses showed that NRF2 is a repressor of NOS2 gene by maintaining a distal enhancer located 22 kb downstream of TSS in an inactive state. Deletion of NRF2 leads to activation of the enhancer, which exerts a pioneering function before it is fully activated.