Projects & Highlights
Optogenetics – The Cyclops:
Neural stimulation has remarkable benefits from activating fiber growth to driving plasticity. However, little is know how activity cooperates with pathways of plasticity. We fabricated a custom chamber for analysis of factors up or down regulated in the axon and target cells for stimulated neural populations. Using microfluidic chambers and LED arrays, we vary the stimulation patterns and examine factors that are modified by activity.
In vivo work is accomplished by inserting a fiber optic probe with a small side-firing window into the spinal canal to examine the effects of optical stimulation of the interneuron population on muscle activity. Using this very novel technique, we optically map the position of stimulation along the spinal column to specific movements. Knowing the location of nerve fibers responsible for coordinating certain movements is critical for specific circuitry repair and reinforcement and exploring the interaction of patterned neural activity with molecular pathways governing plasticity. A 3 camera tracking system is used to track and classify movements due to spinal stimulation.
The Stroke Model:
Using pig stroke models, we study different candidates influencing neural cell fate and neural plasticity, the effects of activity on gene expression in the injured spinal cord, and virtual reality processing/analysis of 3D medical/research data.
Tracking and following neural stem and progenitor cells with a tool that also allows us to change gene expression is a powerful engnineering tool we use alone or in combination with bioengineered materials. A lab-constructed Moloney murine leukemia retro (MMLV) viral vector is used in vitro or injected into the brain or spinal cord of mice/rats to trace myelin regrowth and regeneration in the central nervous system. We also have plans to differentiate human induced pluripotent cells (hiPSC’s) in vitro, and use in our rodent model for spinal cord injury.
Myelin “The Groot” Regeneration
The idea that neural activity influences synaptic plasticity is an accepted tenet of neuroscience. We are exploring a new new and exciting concept that neural activity influences myelin plasticity. Demyelination following a spinal cord injury contributes to functional deficits. Manipulating neural activity in a variety of ways allows us to examine each activity pattern’s effects on myelin and white matter remodeling, which may ultimately lead to a regeneration plan to better functional outcomes and recoveries.
Neural activity patterns are regulated to create behaviors and allow us to adapt to changes in our environment. I am interested in how activity patterns can be manipulated using semi-noninvasive methods to direct regrowth and optimization of injured nerve pathways. We use rodent models of spinal cord injury and multiple methods of activity manipulation. Electrical stimulation of the cortico-spinal tract in rats, while in another exercise is used to increase neural activity in descending motor pathways in mice. In both cases, comparing white matter changes to uninjured and less active controls should help us determine the effects of stimulation on neural activity and myelin regrowth.
Using cutting edge nano delivery systems, we are working to develop novel methods to deliver proteins and drugs that we hope will serve as channels to aid the recovery of patients suffering from various neurological disorders.
The Translation Initiated Volt:
With clinical research partners at Houston Methodist and our global partners, we direct a major effort to move from bench to bedside by engineering new neural circuits in people with chronic paralysis for the restoration hand function. Neural regeneration strategies are also being applied to stroke, head injury, multiple sclerosis, glaucoma and motor/cognitive decline associated with aging