Preclinical Disease Research

The glial and vascular failure modes the lab studies in the device-implant context are mechanistically continuous with the cellular processes underlying multiple sclerosis, Alzheimer's disease, traumatic brain injury, and stroke. Chronic device implantation and parametric stimulation provide controlled, longitudinal access to these processes in healthy adult cortex, an experimental condition disease researchers wish they had in their own preparations.

Multiple Sclerosis

MS is fundamentally a disease of myelin, oligodendrocyte, and OPC biology. The lab's work on activity-dependent oligodendrocyte plasticity, chronic OPC dynamics around perturbation, and pharmacological modulation of myelin (including clemastine, which is an FDA-approved antihistamine being tested in MS clinical trials and which the lab has shown improves chronic recording stability through oligodendrocyte mechanisms) connects directly to MS biology. Collaborator Franca Cambi (Pitt) is a MS researcher and is co-author on the lab's recent oligodendrocyte work, including the FusOLcKO paper (Wellman et al., JNE 2026).

Alzheimer's Disease

Recent single-cell transcriptomic atlases of the AD brain (Mathys et al., Nature 2019, Cell 2023, Nature 2024) have identified oligodendrocytes as among the most transcriptionally altered cell types in AD, with myelin maintenance genes contributing to cognitive resilience and OPC synapse-associated genes specifically perturbed. The lab's work on oligodendrocyte vulnerability and OPC activity-dependent function provides mechanism for these transcriptomic observations. Ongoing collaborative work with the Cambi lab examines Fus-depleted oligodendrocytes in the AppNL-G-F AD model (Tung et al., bioRxiv 2025), establishing direct mechanistic continuity between the lab's basic biology axis and AD oligodendrocyte vulnerability.

Traumatic Brain Injury

TBI produces both acute mechanical injury and a chronic neuroinflammatory cascade, with white matter injury increasingly recognized as a primary determinant of long-term outcome. The lab's framework for understanding implant-induced injury cascades (acute mechanical disruption, chronic foreign body response, glial encapsulation, and oligodendrocyte and OPC vulnerability) maps directly onto TBI biology, with the device context providing parametric control over the injury timeline and severity that TBI models cannot match.

Stroke

Post-stroke recovery depends on neurovascular unit reorganization, white matter remodeling, and microglial regulation of the inflammatory response. The lab's mural cell biology work (Wellman et al., Biomaterials 2025) provides mechanistic insight into how the neurovascular unit responds to chronic perturbation, with implications for understanding how the post-stroke neurovascular unit reorganizes during functional recovery. Collaborative work on focused ultrasound and microbubble-mediated mitochondrial transplantation strategies links to emerging stroke therapeutic approaches.

Why the Device Context Matters for Disease Research

Standard disease models trade experimental control for clinical relevance. The device-implant context offers a complementary experimental setting, parametric, controlled, longitudinal perturbation in healthy adult cortex, which lets the lab dissect cellular and vascular failure modes mechanism by mechanism. The disease relevance arises from mechanistic continuity (the same cells, the same molecular pathways, the same cellular failure modes), not from disease modeling per se. This is the experimental access disease researchers wish they had in their own preparations, and it is the entry point that brings disease-interested quantitative trainees into the lab.