Epigenetic mechanisms regulate gene activity in the brain and are essential for normal brain development and control of the adult brain function. Epigenetic dysregulation has been strongly implicated in psychiatric disorders. Epigenetic modifications, such as DNA methylation and histone modifications, can be affected by both genetic and environmental risk factors and are likely mediators of molecular, structural, and functional changes in the brain involved in the initiation and maintenance of psychopathology. Dr. Kundakovic’s research program integrates molecular, behavioral, structural, and computational  analyses to further our understanding of epigenetic regulatory processes that shape brain and behavior with an emphasis on brain sexual dimorphism. We also study the epigenetic basis of mental disorders with an aim to help tailor novel diagnostic, preventive, and therapeutic approaches in the area of mental health.

Current and future research projects will focus on:

1) Epigenetic Mechanisms underlying Sex Differences in Brain and Behavior. Brain structure and function are sexually dimorphic. Males and females show differences in numerous neural and behavioral phenotypes, including emotion regulation and cognitive function. Within females, behaviors also vary across the menstrual (or estrous) cycle, as fluctuating sex-hormone levels can dynamically change brain structure and function. The current lab project explores the contribution of sex hormones and epigenetic mechanisms to between- and within-sex variation in emotional behavior.

2) Environmental Effects on the Brain Epigenome. Adverse environments, such as stress, toxicological exposures and malnutrition, can increase risk for psychopathology over the life course. The underlying mechanisms are just emerging and likely involve the lasting environmental effects on the brain epigenome which translate into the altered brain structure and function. A current project in Dr. Kundakovic’s laboratory examines the effects of early-life stress, biological sex, and female estrogen status on cocaine addiction vulnerability.

3) Development of Epigenetic Biomarkers to Predict Psychiatric Risk. The epigenome (the collection of all epigenetic marks in a given cell) is largely cell type- and tissue-specific.  However, there is increasing evidence that epigenetic signatures in peripheral tissues (e.g. blood and buccal cells) may be informative of epigenetic signatures in the brain and potentially used to diagnose and predict psychiatric disorders. In collaboration with psychiatrists and clinical psychologists, we perform epigenetic analyses of peripheral tissues of children and adolescents who are at risk for psychopathology in order to develop candidate epigenetic biomarkers for prediction of psychiatric risk.

4) Epigenomic Profiling in Psychiatric Disorders. Epigenetic mechanisms have been strongly implicated in various psychiatric disorders and provide a novel candidate mechanism for intervention and treatment. Yet, the field of psychiatric epigenomics is still missing comprehensive and high-resolution studies. The future focus of the lab will be to use novel epigenomic and bioinformatic approaches to elucidate epigenetic changes associated with psychiatric disorders such as depression and schizophrenia.

Our Research Collaborators:

John Greally and Masako Suzuki, Center for Epigenomics, Albert Einstein College of Medicine

M. Jordan Rowley, Nebraska Medical Center

Amy Roy, Fordham University

Marin Veldic and Barbara Bruce, Mayo Clinic

Heining Cham, Fordham University