Alicia Smith, PhD
Department of Psychiatry & Behavioral Sciences
My research focuses on the role of environmental influences on genetic and epigenetic factors that influence human behavior and psychopathology. Prenatal exposures and early life stress are risk factors for multiple psychiatric and medical problems. For example, prenatal exposure to smoking can modify the influence of a genetic variant in COMT to predict aggressive behavior during adolescence.
Similarly, nutrition, life experiences or environmental toxins can influence the epigenome and subsequent gene expression. We found that prenatal exposure to anti-epileptic medications, but not antidepressants or associate with differences in umbilical cord blood DNA methylation. We are in the process of conducting developmental, neurocognitive and behavioral evaluations in the exposed children between 3 and 5 years of age to assess the long-term impact of prenatal medication exposure.
We have also observed changes in DNA methylation across the genome that associate with gestational age. There is an increased risk for adverse neonatal outcome with declining gestational age even among term deliveries. Notably, these CpG sites were located in genes previously implicated in labor and delivery (e.g., ESR1, AVP and OXT) or that may influence the risk for adverse health outcomes later in life (e.g., DUOX2, CAPS2 and CASP8). We are now attempting to further replicate these findings in a preterm cohort and to evaluate whether the observed methylation changes are stable. These data may suggest a mechanism through which preterm birth acts as a risk factor for multiple childhood or adult onset disorders.
As genome-wide methods rapidly evolve, we have unprecedented opportunities to explore the influence of SNPs, CNVs and epigenetic modifications on gene expression and health-related outcomes. In the future, I would like to continue to develop these studies with an overarching goal of understanding the regulatory mechanisms that influence development.
The purpose of this application is to develop collaborations within the Pediatric Research Center. Towards that goal, I have begun exploring potential collaborations with Warren Jones and Ami Klin to examine DNA methylation within a longitudinal cohort collected at the Marcus Autism Center. Additionally, I am collaborating with Subra Kugathasan to examine DNA methylation in response to varying treatments for Crohn's Disease in a pediatric cohort. It his my hope that these discussion will lead to multiple grant applications.