Research: Applied Engineering

The Two Axes

Axis 1, Tissue-Device Biophysics

How does the brain respond to implanted devices and exogenous perturbation, electrical, ultrasonic, optical, chemogenetic, and pharmacological, at the cellular and vascular level? Axis 1 characterizes the biological cascades that determine device performance over chronic timescales, including the temporal sequence of injury and resolution at the implant interface, the cell-type-specific contributions of microglia, astrocytes, oligodendrocytes and OPCs, mural cells, and endothelial cells, the metabolic and oxygen consumption dynamics that gate sustained neural firing under stimulation, and the mechanical and material properties that determine the foreign body response.

Axis 1 produces mechanism that informs device design, stimulation parameter selection, and clinical deployment through active collaborations with industry partners and clinical neuromodulation programs.

Axis 2, Glial and Vascular Neurocomputation

What computational roles do astrocytes, oligodendrocytes, microglia, and the cerebrovasculature play in healthy brain function, learning, and disease? Axis 2 maps these contributions using two-photon and multiphoton imaging, chronic electrophysiology, electrochemistry, biophysical modeling, and computational analysis. The lab has contributed to the field's understanding of activity-dependent oligodendrocyte plasticity in adult cortex, the dynamics of microglial surveillance under physiological and perturbed conditions, mural cell function in chronic neurovascular coupling, and the metabolic infrastructure that determines sustained neural activity.

Axis 2 builds mechanistic accounts of cortical function that extend beyond the neuron-centric view of neural circuits, with implications for neurological disease as well as for neural interface design.

Bidirectional Coupling

The axes are not parallel tracks. Observations from Axis 1, how implants and parametric stimulation perturb glial and vascular systems, generate hypotheses that Axis 2 tests in basic biology terms. Findings from Axis 2 specify what Axis 1 must engineer to advance the device-tissue interface and the clinical applications it enables. Most papers from the lab contribute to both axes simultaneously.

A working example: the lab's identification of oligodendrocyte and OPC vulnerability around chronic electrodes (Axis 1) generated the hypothesis that activity-dependent myelin remodeling occurs in adult cortex on behavioral timescales (Axis 2 question). Conditional genetic experiments in oligodendrocyte-specific Fus depletion mice (Axis 2 mechanism) demonstrated that altered myelin dynamics affect chronic recording quality differently in cortex versus hippocampus (Axis 1 implication). The same dataset advances both axes, and the trainees on the project develop skills in both directions.

This bidirectional coupling is the operational form of the lab's reverse-translation philosophy. Forward translation, mechanism informs device, is the standard direction in engineering-portfolio research. Reverse translation, device perturbation generates basic biology, is the direction the lab adds and that distinguishes it from labs operating in only one direction.