Decoding the RNA basis of aging and disease

The Maragkakis lab investigates the high-dimensional regulation of gene expression to uncover the mechanistic basis of aging physiology and disease. Its work integrates experimental and computational approaches to study dynamic changes in RNA metabolism and develop interventions to counteract aging-associated decline, cellular senescence, and chronic age-associated pathologies such as neurodegeneration.

The lab develops experimental and computational technologies based on long-read sequencing with single-cell and spatial resolution to capture the native state of RNA in cells, and builds machine learning tools to model fundamental biological mechanisms and design combinatorial interventions to increase human healthspan.

Schematic illustrating the lab's research framework. Top: a pipeline showing how DNA is transcribed and RNA undergoes RNA Processing and Isoform Selection, mRNA Modifications (Epitranscriptome), Translation, and RNA Decay and Turnover — with outcomes including Functional Decline and Aging, Cellular Senescence and SASP, and Neurodegeneration and Disease. Bottom: the integrated approach combining Long-read Sequencing (full-length isoforms, modifications, kinetics), Single-cell and Spatial Transcriptomics (cell-type resolution in space and time), and Machine Learning and Predictive Modeling (mechanistic models, perturbation response). The overarching theme states: Aging is governed by coordinated, low-effect changes in RNA metabolism that reshape gene expression programs across cells and tissues, progressing From Descriptive Changes to Causal Mechanisms to Predictive Models to Therapeutic Interventions.

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