Biology subjects

Saban, D.

Publications and source records attributed to Saban, D..

4 recordsLinked to original sources

bioRxiv2026

stMCP: Spatial Transcriptomics with a Model Context Protocol Server

Spatial transcriptomics enables high-resolution mapping of gene expression in intact tissues but remains challenging due to complex computational workflows that limit accessibility and reproducibility. Here, we present a Model Context Protocol (MCP) framework enabling natural language-driven spatial transcriptomics analysis. By executing analytical tools locally, this architecture eliminates the need to upload massive datasets to large language models, bypassing high token costs and mitigating data privacy and training risks. The MCP orchestrator interprets intent, dynamically routes requests, maintains session state, and verifies input integrity to ensure reproducible execution. Benchmarking across biological discovery, orchestration accuracy, token usage, and execution time demonstrates robust performance. This architecture establishes a scalable template for AI-native research by standardizing the interface between models and local analytical engines. Rather than replacing bioinformaticians, this framework empowers biologists to independently and comprehensively explore their data, accelerating hypothesis testing, and unlocking broader biological discoveries.

bioinformatics↗

bioRxiv2023

Microglia at Sites of Atrophy Restrict the Progression of Retinal Degeneration via Galectin-3 and Trem2 Interactions

Degenerative diseases of the outer retina, including age-related macular degeneration (AMD), are characterized by atrophy of photoreceptors and retinal pigment epithelium (RPE). In these blinding diseases, macrophages are known to accumulate ectopically at sites of atrophy, but their ontogeny and functional specialization within this atrophic niche remain poorly understood, especially in the human context. Here, we uncovered a transcriptionally unique profile of microglia, marked by galectin-3 upregulation, at atrophic sites in mouse models of retinal degeneration and in human AMD. Using disease models, we found that conditional deletion of galectin-3 in microglia led to defects in phagocytosis and consequent augmented photoreceptor death, RPE damage and vision loss, suggestive of a protective role. Mechanistically, Trem2 signaling orchestrated the migration of microglial cells to sites of atrophy, and there, induced galectin-3 expression. Moreover, pharmacologic Trem2 agonization led to heightened protection, but only in a galectin-3-dependent manner, further signifying the functional interdependence of these two molecules. Likewise in elderly human subjects, we identified a highly conserved population of microglia at the transcriptomic, protein and spatial levels, and this population was enriched in the macular region of postmortem AMD subjects. Collectively, our findings reveal an atrophy-associated specialization of microglia that restricts the progression of retinal degeneration in mice and further suggest that these protective microglia are conserved in AMD. One Sentence SummaryA common neuroprotective response of microglia at the site of retinal atrophy is identified in mice and humans.

immunology↗

bioRxiv2021

Midbrain microglia exhibit early proliferative and inflammatory responses during aging that are modulated by CX3CR1 and microglial ablation and repopulation

During aging, microglia produce inflammatory factors, show reduced tissue surveillance, altered interactions with synapses, and prolonged responses to insults, positioning these cells to have profound impact on the functional integrity of nearby neurons. We and others recently showed that microglial attributes differ significantly across brain regions and CNS insults in young adult mice. However, the degree to which microglial properties vary during aging is largely unexplored. Here, we analyze and manipulate microglial aging within the basal ganglia, brain circuits that exhibit prominent regional microglial heterogeneity and where neurons are vulnerable to functional decline and neurodegenerative disease. We demonstrate that microglia in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) exhibit unique and premature responses to aging, compared to microglia elsewhere. This is associated with pockets of VTA/SNc neuroinflammation that are likely to compromise local synaptic function as early as middle age. Surprisingly, these early aging responses of VTA and SNc microglia do not appear to be driven by systemic inflammation, local neuron death, or early responses of astrocytes to aging. Finally, CX3CR1 receptor knockout can exacerbate and microglial ablation/repopulation can suppress early VTA microglial aging; these manipulations have been shown to affect brain-wide microglial aging, and our data demonstrate that their impact is not uniform throughout the CNS. Our findings reveal a previously unappreciated regional variation in the onset and magnitude of microglial aging responses and suggest that there may be important links between local microglial aging and vulnerability of nearby neurons to functional decline and disease.

neuroscience↗

bioRxiv2019

De-novo discovery of tumoricidal aptamers in a DNA sequencing chip

We describe a technique for the rapid ab-initio discovery of target-tailored tumoricidal DNA oligonucleotides inside an Illumina sequencing chip. By sequencing oligonucleotide pools we generate a physical microfluidic map of hundreds of millions of potential oligo clusters, in which every cluster is mapped to a specific set of spatial coordinates. Tumor cells, pre-loaded with a fluorogenic reporter of apoptosis, are then injected into the chip and monitored over time. Apoptotic tumor cells are identified and analyzed across the entire map, automatically revealing the coordinates of oligos that induced this effect. We demonstrate this method by identifying, within just a few hours, new oligos capable of directly and selectively inducing apoptosis in primary human tumor cells. Such a major capability could lead to a new paradigm of personalized cancer therapy.

synthetic biology↗