My name is Jessica Gebhardt, and I am a graduate student in Dr. Josh Morganti’s Lab studying the effects of dysregulated neuroinflammation following traumatic brain injury (TBI). TBI has personally impacted me and my family, and as a result I have been interested in furthering my understanding of the mechanisms underlying the injury for many years. This led me to pursue a career as a scientist focused on studying TBI. I believe this research will have lasting benefits on many people that have suffered the effects of a TBI, which include but are not limited to those who play competitive sports, military personnel, and those with an increased risk of falling such as the elderly. Currently, there are no cures for TBI, and treatment is limited to managing symptoms. My research seeks to target the underlying causes of prolonged symptoms after injury which will hopefully aid in the collaborative scientific endeavor to create a cure for traumatic brain injury.
Historically, the field has focused on neuronal loss after injury, but under Dr. Morganti’s guidance I get to explore the impact TBI has on microglia, the resident immune cell within the brain. Microglia can switch between homeostatic and pro-inflammatory states, and research has shown that after a TBI microglia sustain a more pro-inflammatory phenotype at both acute and chronic stages. This switch is dependent upon microglia’s metabolic state, and proper immune cell metabolism has been shown to be critical for maintaining homeostasis. During injury or disease microglia’s metabolism is negatively altered, which though detrimental, gives us clues into how to reprogram microglia after injury as to restore homeostatic function. The overall goal of this research is that by targeting microglia we can ameliorate lingering symptoms following TBI as well as reduce TBI’s impact as a risk factor for neurodegeneration later in life.
Though this research is still very new, I am able to use cutting edge techniques to explore the function of microglia following TBI. One of these techniques is a mouse model that fluorescently stains a key transcriptional factor in the metabolic cascade that controls microglia’s functional state. This model enables us to visualize specific cell types and timepoints at which the brain is most sensitive to maladaptive metabolic alterations. Following this, another mouse model will be utilized that selectively deletes this transcription factor in microglia. I hypothesize that preventing microglia from undergoing a pro-inflammatory switch will reduce behavioral and cellular dysfunction following an injury. With each mouse model, technology called single cell RNA-sequencing (RNA-seq) will be utilized to obtain the gene expression of the brain. This enables us to classify cells with subtype specificity so that we can distinguish between dysfunctional and homeostatic cells within the brain. Other complementary techniques will be paired with this data to create a mutliomics approach that allows us to understand TBI at a more sophisticated level. In all, the emerging research regarding TBI in the field of Neuroscience is at a pivotal point and the beneficial implications for many people and their families cannot come soon enough.