Biomedical subjects

Ankur Jain

Publications and source records attributed to Ankur Jain.

4 recordsLinked to original sources

PubMed2026

Polyamines buffer labile iron to suppress ferroptosis.

Polyamines are essential and evolutionarily conserved metabolites present at millimolar concentrations in mammalian cells. Cells tightly regulate polyamine homeostasis through complex feedback mechanisms, yet the precise role necessitating this regulation remains unclear. Here, we show that polyamines contribute to endogenous buffering of redox-active iron, providing a molecular link between polyamine metabolism and ferroptosis. Using a genome-wide CRISPR screen, we identified a synthetic lethal dependency between polyamine depletion and the key ferroptosis suppressor, glutathione peroxidase 4 (GPX4). Mechanistically, we show that polyamine deficiency triggers a redistribution of cellular iron, increasing the labile iron pool and upregulating ferritin. To directly visualize this iron buffering in living cells, we developed a genetically encoded fluorescent reporter for redox-active iron. Live-cell analysis revealed a striking inverse correlation between intracellular polyamine levels and redox-active iron at single-cell resolution. These findings reposition polyamines as key regulators of iron homeostasis, with implications for ferroptosis-linked disease states and cellular redox balance.

Ferroptosis↗

PubMed2025

Transcriptome-wide analysis reveals sequence selection to avoid mRNA aggregation in E. coli.

The stability of RNA base pairing and its limited four-letter code create an intrinsic potential for promiscuous RNA-RNA interactions. In vitro, such interactions drive RNA to self-assemble into aggregates. This raises a fundamental unanswered question: within a confined cellular volume at physiological mRNA abundances, how much aggregation would arise from sequence-encoded chemistry alone? Here, we establish this baseline with large-scale kinetic simulations of the E. coli transcriptome. Our simulations reveal that sequence-encoded base-pairing energetics is sufficient to generate a dynamic network of large aggregates, organized by long, multivalent mRNA hubs. Strikingly, evolutionary analysis shows that native E. coli sequences exhibit clear signatures of selection to counteract this propensity: they fold more stably, minimize unstructured regions, and form weaker intermolecular contacts than dinucleotide-preserving controls. These findings demonstrate that maintaining transcriptome solubility has been a significant, previously unrecognized constraint shaping genome evolution, and provide a new lens to interpret cellular RNA management.

Biological Sciences (Biophysics and Computational ↗

PubMed2025

Polyamines buffer labile iron to suppress ferroptosis.

Polyamines are essential and evolutionarily conserved metabolites present at millimolar concentrations in mammalian cells. Cells tightly regulate polyamine homeostasis through complex feedback mechanisms, yet the precise role necessitating this regulation remains unclear. Here, we show that polyamines function as endogenous buffers of redox-active iron, providing a molecular link between polyamine metabolism and ferroptosis. Using genome-wide CRISPR screens, we identified a synthetic lethal dependency between polyamine depletion and the key ferroptosis suppressor, GPX4. Mechanistically, we show that polyamine deficiency triggers a redistribution of cellular iron, increasing the labile iron pool and upregulating ferritin. To directly visualize this iron buffering in living cells, we developed a genetically encoded fluorescent reporter for redox-active iron. Live-cell analysis revealed a striking inverse correlation between intracellular polyamine levels and redox-active iron at single-cell resolution. These findings reposition polyamines as key regulators of iron homeostasis, with implications for ferroptosis-linked disease states and cellular redox balance.

Journal Article↗

PubMed2002

Outcome of 5,000 flexible sigmoidoscopies done by nurse endoscopists for colorectal screening in asymptomatic patients.

OBJECTIVES: There have been several studies to date establishing the efficacy of nurse endoscopists in colorectal screening. However, no such study has ever been conducted in Hawaii. Utilizing the large sample size of our study, we hope to further support endoscopy by nurses as both a safe and cost-effective means of screening for colon cancer. METHODS: This is a retrospective study of the results of more than 5,000 flexible sigmoidoscopies done by nurse endoscopists in the colorectal screening clinic at Kaiser Hospital in Honolulu, Hawaii, between November 1995 and February 2001. These results were separated into normal, non-neoplastic polyps, adenomas, and cancer. RESULTS: The rate of detection of polyps was 13.3% (non-neoplastic and adenomas). Colon cancer was detected in 15 patients (.3% detection rate), of which 8 were carcinoma in situ, 3 were Dukes A, 2 were Dukes B1/B2, and 2 were Dukes C2. Clinically significant lesions (i.e. carcinoma, large adenomas, or atypical adenomas) were found in 1.8% of all patients. There were 8 carcinoids, 1 lipoma, 2 condylomas, and 3 leiomyomas detected. For patients who underwent colonoscopy, no other significant lesions were found in the areas examined by nurse endoscopists. There were no complications, i.e. perforation, bleeding, infection, and death, in any of the patients. CONCLUSION: The results of our study emphasize the importance of being screened for colorectal cancer. Nurse endoscopists can safely and effectively perform screening flexible sigmoidoscopies. By training more nurse endoscopists, we can increase the rate of colorectal screening in a cost-effective manner.

Aged↗