Research Projects

Our research focuses on several major areas within the realm of maternal immune activation during pregnancy:

Immune profiles at the maternal-fetal interface: Mammalian pregnancy is defined by unique immune profiles that involve intercellular coordination across the maternal-fetal interface throughout gestation. This coordination is essential for proper blastocyst implantation and placentation, tolerance of fetal antigen during symbiotic growth and development, and timely labor and parturition. Each of these gestational stages requires responsive immune adaptations within the pregnant mammal in order for a healthy pregnancy to be maintained. Thus, maternal insults during pregnancy that perturb this tightly regulated immune balance pose a teratogenic threat to the developing offspring—even without vertical transmission of pathogens—and are linked to increased rates of neuropsychiatric disorders.

Microglial reactivity and behavioral circuitry: Many neurodevelopmental disorders display altered signatures within microglia cells, the resident immune cell of the brain. These cells, which serve neuroprotective functions through bidirectional communications with neurons and other glia, also guard against invading antigens and can mount significant inflammatory responses when challenged. Microglia are also required for brain circuitry formation and maturation and their actions can mediate behavioral outcomes. Exogenous or endogenous signals that perturb physiological functions of these cells, therefore, can lead to a disruption in microglial-mediated neurodevelopmental processes in utero and subsequent behavioral abnormalities after birth.

Downstream maternal inflammatory and microbial signaling: Inflammatory cascades initiated during live pathogen infections can elicit disruptions far beyond the initial infection site, inducing intestinal immune injury and shifting resident microbial communities. The same is true for systemic immune disruptions caused by psychological stress. A healthy gut microbiome is required for homeostatic neurodevelopment, and aberrant shifts in microbial communities (i.e. dysbiosis) can disrupt early brain development. Dysbiosis within the maternal microbiome can propagate detrimental intestinal immune signaling pathways which can extend to the fetal compartment and influence maturation of developing embryonic microglia.

Using animal models of maternal immune activation, our work strives to answer the following overarching research questions:

  1. How and which inflammatory signals originate within maternal tissues and how are these signals propagated across the maternal-fetal interface?
  2. How are microglia regulating the early stages of neural network formation and the manifestation of aberrant behaviors?
  3. How might endogenous maternal microbes be communicating, directly or indirectly, with the fetal compartment?
  4. What common endocrine, immune, and neural correlates exist between models of pathogen infection and models of prenatal stress?