Research Projects

We study the neural-immune mechanisms by which early-life immune activation (both bacterial and viral) can disrupt the development of important neural circuits that control learning, and how these mechanisms and effects may be different between males and females.

Sex differences in response to neonatal immune activation

We examine how neonatal males and females respond to events that challenge the immune system and what the consequences of this immune activation may be on later-life brain and behavior. Are males more vulnerable to immune activation early in development? Does this vulnerability increase the risk of learning disabilities and other developmental disorders, which are more prevalent in boys than in girls?

Neuroinflammatory processes associated with neonatal Hypoxic Ischemic Encephalopathy (HIE)

Collaborators:

Dr. Elizabeth Wright-Jin (Nemour's Children's Hospital) 

Dr. Brian Kwee (Biomedical Engineering, University of Delaware)

Neonatal hypoxic ischemic encephalopathy (HIE) is the most common cause of cerebral palsy in children born at term. Affected children are also at significantly increased risk of learning disorders, intellectual disability, ADHD and Autism and these neurodevelopmental impairments can result in lifelong disability. HIE can be caused by any condition that impairs blood or oxygen delivery to the fetal brain around the time of birth, including maternal infection or inflammation, placental insufficiency/abruption, chorioamnionitis, among other factors. Therefore, it is critical to develop a complete understanding of the mechanisms of injury to develop novel or augmentative therapeutic agents. 

Role of small bacterial fragments from the microbiome in brain-immune communication.

Collaborator: 

Dr. Catherine Grimes (Chemistry & Biochemistry, University of Delaware)

Unlike most of the body’s organs, the brain exists behind a blood-brain barrier designed to minimize the passage of cells and pathogens into delicate neural tissue. Yet, our body is colonized with a vast array of commensal bacteria known as the microbiome, and a plethora of growing data highlight an important relationship between the composition of the microbiome and various brain disorders including Alzheimer’s disease, depression and autism. The molecular mechanisms of this intriguing relationship are relatively unknown. Our proposed experiments will determine whether the small cell wall metabolites produced by these bacteria gain access to the brain, and if they do, what do they do there? To date, it’s been assumed that communication between the microbiome and the brain is exclusively indirect, occurring via communication with the endocrine, immune and autonomic nervous systems. We hypothesize, rather, that small carbohydrate fragments derived from the cell wall of the microbiota can translocate to the brain thereby directly and continuously influencing brain function and health.