Lab Overview
The Lane-Donovan Lab investigates the mechanisms that drive aging-related neurodegenerative disease, with a focus on Alzheimer’s disease and frontotemporal dementia. Our central hypothesis is that endolysosomal dysfunction contributes to selective vulnerability in the aging brain and that understanding where and in which cells these changes occur will reveal tractable points for intervention.
In our prior work, we established a direct connection between lysosomal dysfunction and clinically used Alzheimer’s disease biomarkers (Lane-Donovan et al., 2025). We are now extending this work through mechanistic in vitro studies designed to pinpoint the molecular pathways that drive these biomarker changes and to clarify what they reveal about disease biology.
Our overarching goal is to identify novel therapeutic targets and improve the mechanistic interpretation of biomarkers that are already shaping clinical research.
We are hiring postdoctoral fellows and specialists for these projects.
Focus 1: Cell-type and brain region specificity of endolysosomal dysfunction in aging and neurodegeneration
The brain is not uniformly affected by aging or disease. Some regions and cell populations show early vulnerability, while others remain comparatively resilient. We use mouse and iPSC-derived human CNS models to define cell-type– and region-resolved differences in endolysosomal function across aging and neurodegenerative conditions.
Key questions we pursue include:
Which cell types show the earliest or most consequential endolysosomal changes during aging?
Are lysosomes in selectively vulnerable brain regions altered, and what cellular features explain that vulnerability?
Which steps in endolysosomal pathways become disrupted—and how do those disruptions contribute to disease onset or progression?
By mapping these changes with specificity, we aim to identify mechanistic nodes that can be targeted to restore cellular homeostasis and protect the aging brain. Our group uses confocal imaging, single cell RNA sequencing, and viral mediated gene delivery to answer these questions.
Focus 2: Mechanistic interpretation of clinically used serum biomarkers and identification of novel biomarkers
Serum biomarkers are increasingly used in clinical research and care for neurodegenerative diseases, yet key questions remain: What biological processes do these markers truly reflect? Which molecular pathways drive biomarker changes over time? How do biomarker trajectories relate to specific cellular dysfunction in the brain?
We utilize in vitro protease cleavage assays and iPSC-derived CNS cell types to study clinically used serum biomarkers with the goal of grounding them in molecular mechanisms. Key questions we want to answer include:
Which underlying pathways generate these biomarkers?
Can we interfere upon these pathways to modulate disease upstream of tau and amyloid?
Could we identify better candidate biomarkers using the mechanisms we have identifed?
Ultimately, we aim to make biomarkers more informative—not only as correlates of disease, but as tools that meaningfully report on mechanism and therapeutic engagement.
Lab Values
Our lab values are service, community, and rigor. We are committed to fostering an environment that is supportive, inclusive, and collaborative, where trainees and staff can do their best work to improve how we treat and diagnose neurodegenerative diseases of aging. We value scientific integrity, open communication, and thoughtful mentorship.