Senior Research Career Scientist

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Overall goals: My laboratory strives to understand and facilitate the neuroinflammatory response to all implanted devices within the central nervous system. Such devices range from ventricular shunts to various types of stimulating and recording electrodes. However, most of my efforts have been on intracortical microelectrodes due to their significance in research to understand the brain and the role in rehabilitative applications of Brain Computer Interfacing, which is of particular interest to the VA. By understanding mechanism of failure, we can pursue both materials-based and therapeutic-based methods to mitigate the inflammatory-mediated failure. 1) Role of tissue/device mechanical mismatch in microelectrode failure. We developed biologically inspired materials for intracortical microelectrodes to independently examine and manipulate device modulus, geometry, and drug-eluting capabilities. We have demonstrated that mechanically dynamic intracortical microelectrodes are stiff enough to be inserted into the brain, become compliant to reduce micro-motion and inhibit late-stage neuroinflammatory responses, can be fabricated into functional intracortical microelectrodes, and can be utilized to deliver anti-inflammatory therapeutics from the device substrate or in combination with microfluid devices. 2) Role of oxidative stress in microelectrode failure. Oxidative pathways have been implicated in both neurodegeneration and corrosive damage to both the metallic and insulating materials of current intracortical microelectrode technologies. Thus, approaches to mitigate or attenuate the deleterious effects of oxidative inflammatory products are of significant importance. We have demonstrated that several antioxidants can be delivered systemically or locally to temporally mitigate neuronal damage and loss, and that bioactive coatings with mimetic anti-oxidative enzymes can prolong neuroprotection and improve recording performance. 3) Role of specific immunity pathways in microelectrode failure. Pathological assessment of the neuroinflammatory response to intracortical microelectrodes has been limited to a dozen or so known neuroinflammatory proteins. We are using spatially resolved omics to developed one of the most comprehensive analyses to date the microelectrode/tissue interface. By identifying genes and proteins of interest, we can then explore hypotheses about specific innate immune systems or develop gene therapies for immune cell silencing. 4) Role of gut microbiome in microelectrode failure. Microbiome may play a role in modulating neuroinflammation. Constituents of the gut microbiome can directly infiltrate the brain causing a local inflammatory response, or act indirectly via metabolites or inflammatory factors that enter the blood stream and cross the blood brain barrier. We utilized 16S rRNA analysis to show that the composition of gut-resident microbiome in feces and brain tissue changes following microelectrode implantation and can be modulated through treatment to impact the quality of chronic intracortical recordings. We seek to translate these findings from preclinical to clinical therapies to improve microelectrode performance.