Biology subjects

Farah, N.

Publications and source records attributed to Farah, N..

3 recordsLinked to original sources

bioRxiv2026

Retinal resuscitation in post-mortem eyes

Vision loss compromises the quality of life of millions of people worldwide. Currently, vision-restoring therapies are lacking. Post-mortem preservation of human eyes may enable whole eye transplantation (WET) or therapeutic development. We developed an approach to cannulate the ophthalmic artery and perfuse post-mortem pig and human eyes using a custom-built device, Eye-in-Care-Box (ECaBox). Retinal vasculature imaging and reconstruction were used to assess perfusion efficacy using a supervised deep learning model. Without intervention, the retina degrades post-mortem, whereas perfusion preserves retinal structure and cell viability for up to 24-hours. Eyes were perfused within 30 minutes post-extraction, and regained light-responses persisted for up to 10 hours after death, challenging the notion that response to light ends at death. Our findings show that intact eyes can be resuscitated and preserved outside the body, supporting the ECaBox platform for WET preservation and pre-clinical therapeutic testing. Ultimately, ECaBox may bring vision-restoring treatments to patients.

neuroscience↗

bioRxiv2024

Optogenetics-integrated gut organ culture system connects enteric neurons dynamics and gut homeostasis

The enteric nervous system (ENS) senses microbiota-derived signals and orchestrates mucosal immunity and epithelial barrier functions, in health and disease. However, mechanistic dissections of intestinal neuro-immune-microbiota communications remain challenging and existing research methods limit experimental controllability and throughput. Here, we present a novel optogenetics-integrated gut organ culture system that enables real-time, whole-tissue stimulation of specific ENS lineages, allowing for detailed analysis of their functional impact. We demonstrate that optogenetic activation of enteric cholinergic neurons rapidly modulates intestinal physiology. Interestingly, distinct neuronal firing patterns differentially modulate neuro-immunological gene expression and epithelial barrier integrity. Furthermore, diverse enteric neuronal lineages exert distinct regulatory roles. While cholinergic activation promotes gene-sets associated with type-2 immunity, tachykininergic enteric neurons differentially control mucosal defense programs. Remarkably, luminal introduction of the immunomodulatory bacterium C. ramosum significantly remodeled cholinergic-induced neuro-immunological transcription. These findings suggest that complex combinatorial signals delivered by gut microbes and enteric neurons are locally integrated to fine-tune intestinal immunity and barrier defense. Collectively, we provide a powerful platform for systematic discovery and mechanistic exploration of functional neuroimmune connections, and their potential modulation by drugs, microbes, or metabolites. Short abstractThe enteric nervous system senses microbiota-derived signals and orchestrates mucosal immunity and epithelial barrier functions. Mechanistic dissections of intestinal neuro-immune-microbiota communications remain challenging. We developed an optogenetics-integrated gut organ culture system for real-time neuronal stimulation and analysis. We revealed neuronal-specific activity patterns, which differentially regulate intestinal transcription and epithelial barrier integrity. Collectively, we provide a powerful platform to test neuroimmune connections and their potential modulation by drugs, microbes, or metabolites.

neuroscience↗

bioRxiv2024

Focal Deletions of a Promoter Tether Activate the IRX3 Oncogene in T Cell Acute Lymphoblastic Leukemia

Oncogenes can be activated in cis through multiple mechanisms including enhancer hijacking events and noncoding mutations that create enhancers or promoters de novo. These paradigms have helped parse somatic variation of noncoding cancer genomes, thereby providing a rationale to identify noncanonical mechanisms of gene activation. Here we describe a novel mechanism of oncogene activation whereby focal copy number loss of an intronic element within the FTO gene leads to aberrant expression of IRX3, an oncogene in T cell acute lymphoblastic leukemia (T-ALL). Loss of this CTCF bound element downstream to IRX3 (+224 kb) leads to enhancer hijack of an upstream developmentally active super-enhancer of the CRNDE long noncoding RNA (-644 kb). Unexpectedly, the CRNDE super-enhancer interacts with the IRX3 promoter with no transcriptional output until it is untethered from the FTO intronic site. We propose that promoter tethering of oncogenes to inert regions of the genome is a previously unappreciated biological mechanism preventing tumorigenesis.

cancer biology↗