Research Focus
Basic Science Research Topics
- Development and maturation of neural circuits that underlie social-emotional behavior and learning
- The impact of early life stress on forebrain and vagal circuits and behavior
- Genetic factors that impact phenotypic heterogeneity
- Molecular adaptations to prenatal and early postnatal experiences
Clinical Research Topics
- Clinical studies of the impact of early life experiences impacting infant and toddler brain and behavioral development
- Clinical studies of biomarkers of resilience, toxic stress and response to interventions
- Clinical studies of infants at risk for autism spectrum disorder (ASD), and children with medical complications who have an ASD diagnosis
Research Overview
The research projects in our laboratory are driven by a talented group of faculty, postdoctoral fellows, graduate students, research staff and collaborators. Our laboratory is unique in performing both basic and clinical research projects that inform each other. Research projects investigate the development of brain architecture that controls social-emotional behavior and learning, and how early life experiences impact neurodevelopment.
The basic science projects are focused on understanding the biological basis of neurodevelopmental and neuropsychiatric disorders, and how genes and prenatal and early postnatal environments together influence typical and atypical development. We study the mechanisms that underlie the differentiation of the complex diversity of cell types in the neocortex and the autonomic brain. Genetic and environmental factors that regulate circuit and synapse formation are studied at the molecular and circuit level, using single cell RNA sequencing, viral circuit tracing, multiplex in-situ hybridization, proteomics and mass spectroscopy analyses of metabolic adaptations. We collaborate with other laboratories to apply advanced electrophysiological methods to understand changes in synapse maturation and plasticity. The preclinical mouse models combine genetic manipulations and exposure to early adverse experiences to study the impact on circuit wiring, cellular physiology impacted by oxidative stress, and the development of cognitive, social and emotional behaviors. Genetic reference panels of mice are used to decipher the role that different genomes play in mediating the penetrance and severity of disease-causing single gene mutations (e.g., ChD8 in autism).
The clinical research programs focus on understanding the impact of early experiences, both positive (resilience) and negative (early life adversities) on healthy brain and child development. The research program also includes studies of healthy development and autism spectrum disorder (ASD). Our current work focuses on developing biomarkers for early life adversities in healthy infants and early identification of autism. In the past, we have also studied gastrointestinal disturbances in children with ASD to determine metabolic and immune biomarker changes pre- and post-intervention in collaboration with treatment experts. All of these projects are performed using interdisciplinary research methods and data analytical approaches.
Family First Research Study
The Family First Study has a goal of scaling biomarker and data collection methods to determine whether infants experiencing early life adversity exhibit changes to their metabolic health. Families are recruited from collaborative pediatric practices and community partners throughout Los Angeles and Ventura counties. There is a focus on mitochondrial (mt) measures, using advanced assays for mtDNA and mtRNA, in partnership with the Center for Personalized Medicine at Children’s Hospital Los Angeles. The study also includes high-resolution eye tracking of infants to assess development of attention systems, parent questionnaires that address resiliency, social connectedness, access to social services, family routines, and parental stress and emotional state. The study uses a play-based infant developmental assessment and a mother-infant interaction task. This work is supported by the California Initiative to Advance Precision Medicine – Adverse Childhood Experiences research grant program. For more information, please see our Family First Research Study Flyer or contact FamilyFirst@chla.usc.edu.
Collaborators
Kamitakahara Laboratory
Principal Investigator
About
The brain and the gut are inextricably linked. This is evident in the way stress can leave you with the feeling of butterflies in your stomach. Collaborative research between the Levitt and Kamitakahara labs investigates the development of the vagus nerve that serves as a major conduit for this information communicated from the gut to the brain and vice versa. Specifically examined is the impact of early life stress on vagal circuit growth, connectivity, and function. Mechanistic understanding of vagal gut-brain axis development is probed using advanced techniques such as single cell RNA sequencing, highly multiplexed in situ hybridization, and behavioral assays. Through delineation of the signals that guide vagal development as well as the vulnerabilities presented by perinatal stress, our collaborative work aims to understand the biological mechanisms that put children experiencing early childhood trauma and adversity at greater risk for autonomic dysregulation, and gastrointestinal and psychiatric disease.
TREND Laboratory
Principal Investigator
About
The TREND Lab uses multi-method approaches, including electroencephalogram (EEG), behavioral observation and clinical interviews to study risk and protective factors for depression, suicide, and other mental health outcomes in youth with autism and other neurodivergent conditions. We also partner with autistic and other neurodivergent people to adapt and design treatments for the individual and family. The TREND Lab focuses on characterizing and treating adverse mental health outcomes in youth with autism and other neurodivergent conditions.
In the News – Press Releases and Features
- Children’s Hospital Los Angeles Chief Scientific Officer Named to California Stem Cell Research Body Governing Board
- Children’s Hospital Los Angeles, Geffen School Receive Funding
- Critical Windows When Experience Shapes the Brain
- Neurodevelopment of a 2-Month-Old Infants Shows Effect of Maternal Stress
- Common Psychiatric Disorders Share an Overlapping Genetic Risk
Funding
- National Institutes of Health
- National Science Foundation
- The JPB Foundation
- The Simms/Mann Family Foundation
- The WM Keck Foundation
- California Initiative to Advance Precision Medicine
- The Saban Research Institute, Children’s Hospital Los Angeles
