A closed-loop framework linking mechanism discovery, rejuvenation, and therapeutic development for brain aging and neurological diseases
Pinpointing the Road to Degeneration
Systems-level decoding of aging and neurodegeneration β defining where, which, how, and when regulation systems fail across cell populations, molecular layers, and temporal dynamics (lifetime and circadian scales).
Multi-layer regulatory dysregulation: Integrative framework for decoding multi-layer molecular dysregulation across brain aging and neurological disease. Establishing population-scale single-cell and spatial foundations spanning genome, epigenome, and transcriptome.
Circadian disruption & temporal dynamics: Decoding circadian disruption in brain aging and neurodegeneration β mapping cell-type-specific circadian regulatory programs, AI-driven circadian time prediction, and circadian misalignment in disease.
Transposable elements & genomic dark matter: Regulatory circuitry of transposable elements in the brain and their dysregulation linking epigenomic erosion to LINE1 activation and cellular vulnerability in neurodegenerative disease.
Reopening the Road to Rejuvenation
From degeneration to regeneration β restoring cellular and tissue function to counter degeneration. An integrative framework bridging single-cell genomics, multi-omics, biomedical informatics, and experimental validation.
Safeguarding the genome and epigenome: Nuclear guardians of genomeβepigenome integrity. Multimodal "Regulatory Funnel" model to discover novel epigenomic regulators and stabilizers; AI screening of candidate stabilizers using in silico models and 3D human systems.
Targeted Cellular Rejuvenation & Regeneration: Resetting glial fate to restore repair-supportive capacity. Defining glial activationβexhaustion trajectories, identifying fate-shifting regulators, and glial engineering for niche restoration and tissue regeneration.
Navigating from Predictive Modeling to Therapeutics
An integrated framework from degeneration to regeneration and therapeutic design β leveraging AI foundation models, generative inference, and drug discovery.
Modeling & prediction of aging: Single-cell and spatial foundation models for prediction at individual, cell, and spatial hotspot/niche levels. Biological interpretability for mechanism, cellular basis, molecular hallmarks, and therapeutic targets. Ultimate goal: non-invasive prediction.
"Virtual Aging Brain" β GenAI: Cross-modal generative genomics inference and in silico perturbation using perturb-encoder/decoder architecture. Generate testable hypotheses, candidate intervention targets, and rejuvenation strategies.
Therapeutic design & evaluation: AI-guided drug discovery and repurposing, in vitro 2D + 3D organoid perturbation + imaging, in vivo validation, and translational potential.
