Focus Areas in the Genomic Medicine Cycle
Major leadership positions

Senior Fellow, Harvard Center on the Developing Child

Associate Member, Broad Institute of MIT and Harvard

MGH Unit(s)

Psychiatric and Neurodevelopmental Genetics

MGH Dept/Division/Unit(s)

Psychiatry

Pediatrics

Overview

Identify strategies to prevent depression & promote brain health over the lifespan

Our research seeks to understand the drivers of both mental illness and mental wellbeing across the lifespan. Much of our work has focused on the social and biological underpinnings of depression and anxiety among women, children, adolescents, and other vulnerable populations, including racial/ethnic minorities and people of low socioeconomic status.

We study a range of biological factors and processes contributing to mental health—including the role of genetic variation and epigenetic mechanisms—as well as biological markers of future risk, such as markers captured in children’s primary (or baby) teeth.

We study multiple social factors, including the role of early life environmental exposures and stressors such as childhood adversity, on mental health.

Priority Projects

  1. Identifying individuals most at risk for depression. Experts have known for decades that exposure to stress is one of the biggest risk factors for depression. However, not everyone who experiences stressors, including childhood adversity, goes on to experience mental health problems. Further, we don’t yet know which individuals might be more susceptible to, or at risk for, developing depression following a stressful event. Given that depression is known to be partially genetically determined, we study the role of genetic variation in shaping risk for depression, by asking which genes confer an increased susceptibility to the effects of stressful life events. Using prospective data gathered over many years from large birth cohorts in the US and globally, we’re exploring the genomic predictors of depressive symptom trajectories from childhood to adolescence.
  2. Understanding how stress gets biologically embedded. Although we know that people are more likely to develop depression after experiencing a stressor, we don’t yet know how stress “gets under the skin” or causes biological changes to create this long-term vulnerability. We’re working to understand the mechanisms linking stress to depression risk by identifying biomarkers, such as epigenetic signatures, that do not alter the sequence of the genome, but rather shape how genes are expressed. Our currently funded work in this area is exploring how early exposure to stressors—including poverty, child maltreatment, and other adversities—can leave epigenetic marks known as DNA methylation (DNAm) changes, which in turn can increase risk for depression in childhood, adolescence, and even adulthood. Understanding the biological pathways connecting stress to depression can help us better understand the causes of depression and therefore focus our interventions on potentially modifiable biological targets.
  3. Determining sensitive periods in development. There is a growing body of evidence from our research group and others to suggest that the impact of certain exposures on mental health outcomes might depend on whether those exposures occur during “sensitive periods” in development. Sensitive periods are high-risk/high-reward stages during the lifespan when the brain is highly plastic and when life experiences, whether exposure to adversity on the one hand or health-promoting interventions on the other, can have lasting impacts on brain health. Using large-scale data from birth cohort studies, we’re working to identify when these sensitive periods occur and how they shape risk across multiple domains—spanning social-emotional skills (e.g., emotion recognition, social cognition), biological processes (e.g., epigenetic changes), and risk for depression.
  4. Looking at teeth as biomarkers of stress and trauma. The Dunn lab is actively exploring the use of teeth as novel biomarkers of past stress exposure, the timing of those exposures, and future mental health risk. Teeth represent a promising new tool for identifying sensitive periods because they preserve a kind of “fossil record” of their growth and disruptions to that growth, like rings in a tree marking its age.  After determining when these sensitive periods occur, our ultimate goal is to design interventions that not only promote brain health across the lifespan but are also uniquely timed to minimize the consequences of stress exposure and prevent depression years before it onsets.

Lab Members

Name:Email:Role:
Alison Hoffnagle, MSahoffnagle [@] mgh.harvard.eduProgram Director
Alexandre Lussier, PhDALUSSIER [@] mgh.harvard.eduPostdoctoral Fellow
Theresa Cheng, PhDTWCHENG [@] mgh.harvard.eduPostdoctoral Fellow
Mona Le Luyer, PhDPostdoctoral Fellow
Simone Lemmers, PhDPostdoctoral Fellow
Madison BiglerClinical Research Coordinator
Nitasha SiddiqueNSIDDIQUE [@] mgh.harvard.eduClinical Research Coordinator
Samantha StollSSTOLL1 [@] mgh.harvard.eduClinical Research Coordinator
Grace BurkeCo-op Student
Andrew Smith, PhDCollaborating Scientist, University of West England, Bristol, United Kingdom
Yiwen Zhuyzhu14 [@] mgh.harvard.eduCollaborating Scientist
Lab/Contact Telephone

617-726-9387

Primary Email
Lab Website