LysosomalBiology

Axis 1 primary, Axis 2 secondary. A focused thrust on lysosomal and autophagy biology around chronic implants, with translational arms in lysosomal storage disease and neurodegenerative disease cellular quality control.

Open Scientific Question

How does lysosomal and autophagy function in glia and neurons around chronic implants determine cellular quality control, and can targeted modulation of lysosomal pathways extend chronic device function while preserving cellular health? Lysosomal dysfunction is increasingly recognized as a central mechanism in neurodegenerative disease (including AD and Parkinson's disease) and in lysosomal storage disorders, but its role at the chronic device-tissue interface has been minimally characterized. The lab's framework treats the device interface as an in vivo perturbation context for studying lysosomal biology, with direct forward-translation implications for device design and reverse-translation implications for understanding lysosomal dysfunction in disease.

Anchor Papers from the Lab

•         Chen K, Garcia C, Kiselyov K, Kozai TDY. Cell-specific alterations in autophagy-lysosomal activity near the chronically implanted microelectrodes. Biomaterials, 2023, 302, 122316. The first cell-type-specific characterization of autophagy-lysosomal pathway activity around chronic implants, identifying differential responses across glial and neuronal populations.

Disease and Translational Connections

•         Lysosomal storage diseases. The lab's work on cell-specific lysosomal modulation around chronic implants generates mechanism that informs hypotheses about lysosomal storage disease pathophysiology, particularly in cell types (glia) that are difficult to study in vivo through other means.

•         Alzheimer's disease and Parkinson's disease. Lysosomal dysfunction is a central feature in both diseases, with proteinopathy aggregation linked to autophagy-lysosomal pathway disruption. The lab's chronic perturbation context provides experimental access that disease models cannot match.

•         Engineering implication. Targeted modulation of lysosomal pathways at the chronic device-tissue interface offers a forward-translation pathway for extending chronic device function. The NSF 2552758 award develops this strategy directly.

Skills Developed by Trainees on This Thrust

•         Cell-type-specific autophagy and lysosomal readouts, including in vivo and fixed-tissue approaches

•         Pharmacological and genetic modulation of lysosomal pathways

•         Integration of lysosomal biology with chronic implant function and longitudinal electrophysiology

•         Collaboration across cell biology and bioengineering, with direct mentorship from Dr. Kiselyov and other Pitt cell biology faculty

•         Translational framing of device-interface biology for disease applications