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. Here are a few examples of our clinical research projects:
StARS Project
The Study of Autism Risk in Siblings (StARS) focuses on developing biomarkers for early identification of autism in infants and toddlers and is led by Dr. Sahana Nagabhushan Kalburgi. The project applies a multi-modal research strategy of high density recording of brain activity (EEG), simultaneous eye tracking, and developmental assessments. Data-driven advanced analytics are applied to the “big data” in order to identify brain developmental trajectories that are indicative of later onset ASD. This work is supported by a fellowship from The Saban Research Institute and autism research funds from the Division of Research on Children, Youth and Families at CHLA. For more information about this study, please see our study flyer or contact stars@chla.usc.edu.
Resiliency to Toxic Stress
The study, led by Dr. Alma Gharib and Dr. Nagabhushan Kalburgi, is part of a large research consortium with Harvard’s Center for the Developing Child through a grant from The JPB Foundation. Our longitudinal studies of infants include assessment of attention by modern eye-tracking methods, measures of brain wave activity using EEG, questionnaires, and play-based developmental assessment and mother-infant interaction task. The study includes measures of oxidative stress in mothers and infants at high risk for early life adversities. For more information about this study, please see our study flyer or contact yourbaby@chla.usc.edu.
Family First Research Study
The study, led by Dr. Alma Gharib, 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 about this study, please see our study flyer or contact yourbaby@chla.usc.edu.
The HEART Project
The Hispanic Education and Research Team (HEART) project is developing a new research program between the Mexican Consulate of Los Angeles and The Saban Research Institute. The goal is to gain a greater understanding of family well-being, to bring fresh knowledge to families about the research process, and to close the large gap in opportunities for children and their families to participate in research. Collaborative efforts have developed a questionnaire-based survey to establish a database of information that will be used by the Mexican Consulate to assist in determining priorities for services provided to families, and by the research team to inform efforts in establishing more meaningful relationships with families who may be interested in learning about participation in research projects at Children’s Hospital Los Angeles.
Lab Team
Basic Science Team
Kathie Eagleson, PhD
Research Associate Professor
Primary research projects:
- Development of neuronal diversity, neural circuitry and synapses in neocortical networks
- Impact of early adverse experience on brain development
- Influence of sex on response to early life stress
Kathie Eagleson received her PhD from University of Sydney. Her research has two primary focuses. The first examines the role of the MET tyrosine kinase receptor in synapse development and circuit formation. This research includes studies to determine the specific cerebral cortical circuits which are most dependent upon MET for development. Disruptions in the expression of this receptor are associated with an increased risk for autism spectrum disorder and Rett syndrome. Currently, she is using a single-cell RNA sequencing approach to identify transcriptomic signatures of MET-expressing cells. The second project measures the sex-dependent effects of early life stress on the developing brain using an established limited-bedding mouse model. Specifically, Kathie is using proteomics, biochemical and anatomical approaches to determine acute (before puberty) and long-term (adult) adaptive responses in mitochondrial and metabolic function following early life stress.
Anna Kamitakahara, PhD
Assistant Professor of Research
Primary research projects:
- Impact of early life experience on vagal neurons and circuits
- Modeling neural development of gut-brain circuits using human iPSCs
Anna Kamitakahara received her PhD in Neuroscience from the University of Southern California. Her research focuses on understanding the functional organization and perinatal development of the vagus nerve that connects the brain and the gut. She is working to advance the field in her two ongoing projects that examine the impact of early life stress, and the early life nutritional environment on developing vagal sensory and parasympathetic nervous system circuits.
Manal Tabbaa, PhD
National Science Foundation Postdoctoral Research Fellow in Biology
Primary research project:
- Integrating genetic reference panels with neurodevelopmental models to discover mechanisms regulating behavioral heterogeneity.
Manal Tabbaa received her PhD in Neuroscience from Florida State University. Manal’s research leverages genetically diverse reference panels to model individual differences in complex behaviors and susceptibility to a high-confidence autism-risk gene. The goal of these projects is to address the challenging but highly significant issue of clinical heterogeneity and genetic risk factor susceptibility in neurodevelopmental disorders.
Ramin Ali Marandi Ghoddousi, MS
PhD Candidate, University of Southern California
Primary research projects:
- The role of combinatorial trophic factor signaling on vagal motor neuron differentiation and survival
- Transcriptomics of the developing murine cortex
- Tool development for spatial gene expression
Ramin Ali Marandi Ghoddousi received a Master’s of Science in Neuroscience from Brandeis University, and is a PhD student in the USC Neuroscience Graduate Program. Ramin is investigating how combinatorial molecular signaling drives vagus nerve development. His dissertation project will determine how MET and other developmentally important genes work together to differentiate vagal motor neurons into distinct, functionally varying subpopulations. He is using a murine model to determine how early disruption of these genes leads to anatomical and functional deficits. Ramin hopes that the results of these investigations will help elucidate how early developmental mechanisms can lead to proper functional outcomes in phonation, digestion and metabolism.
Alexandra Lanjewar, BS
PhD Candidate, University of Southern California
Primary research project:
- Development and plasticity of cortical circuits mediating cognitive functions
Alex Lanjewar received a BS in Neuroscience from University of Miami and is a PhD student in the USC Neuroscience Program. Her research interests are centered around investigating biological mechanisms that contribute to typical brain development and onset of cognitive functions, with a broader interest in what goes awry in neurodevelopmental disorders. Alex's research focuses on the expression patterns and role of MET receptor tyrosine kinase (MET) in the cortex during development. Studies include determining and comparing MET expression patterns across developmental ages in different cortical brain regions, which give insights into the circuits that MET is normally involved in during development. Studies also include investigating MET as a candidate for regulating the timing of critical period plasticity for onset of long-term fear memories.
Amanda Whipple, AA
Associate Research Specialist
Primary research projects:
- All projects using mouse models of neurodevelopmental disorders
Amanda Whipple received an Associate's Degree in Business at Western International University. Her primary responsibility is to manage the neurodevelopmental models in our colonies. She ensures the health and well-being of our colonies, including appropriate maternal care following pregnancies. Amanda performs nearly all of the genotyping of the genetic lines to determine those who carrying gene mutations. She also serves as the primary liaison with the Division of Animal Care at both CHLA and USC; the latter is where our behavioral studies are performed, and at CHLA where our developmental neuroanatomical, biochemical and molecular studies are undertaken.
Meaghan McCoy, BA
Research Assistant
Primary research projects:
- Impact of early life experience on vagal neurons and circuits
- Modeling neural development of gut-brain circuits using human iPSCs
Meaghan McCoy received a BA in Biological Anthropology from Long Beach State University. She is currently working on two projects related to the development of the vagus nerve. The first aims to investigate the impact of early life stress on the development of vagal neurons and circuits using a limited-bedding mouse model. The second aims to construct a model for the development of vagal connections in the gut using an array of visualization techniques in both human and mouse-derived tissues. Meaghan’s research interests primarily focus on the impact of culture and socioeconomic status on brain development. She hopes to use her research to help advocate for better and more accessible social welfare programs for underserved populations.
Zuhayr Khan, BS
Research Assistant
Primary research projects:
- Development of neuronal diversity
- Neural circuity and synapses in neocortical networks
- Role of a dopamine regulating phosphoprotein in a particular sensory area
Zuhayr Khan received a BS in Biotechnology from California State Polytechnic University, Pomona. During his time at Cal Poly, he led research regarding the strengthening of one's cognitive reserve as well as studying resilience factors to neurodegeneration. Joining the Levitt Lab in July 2021, Zuhayr's research focus has shifted to the opposite spectrum of aging, now investigating neurodevelopment via the temporal and spatial expression patterns of a tyrosine kinase receptor involved in synapse development and circuit formation. He is also interested in the expression patterns of a dopamine regulating phosphoprotein and its role in a particular sensory area of the brain. The combination of Zuhayr's previous and current experience has shaped his perspective of brain functioning to become more holistic. With this new understanding, he plans on pursuing a PhD in Neuroanatomy/Systems Neuroscience to become a professor and to educate, research, and lead.
Clinical Research Team
Alma Gharib, PhD
Clinical Research Director
Primary research projects:
- Healthy baby development and resilience to toxic stress
- CIAPM ACEs Family First Study
Alma Gharib received a PhD in Biology with an emphasis on Social Neuroscience from California Institute of Technology. Her research is focused on social and developmental neuroscience, and she has over 10 years of experience using eye-tracking to investigate social development. Alma directs clinical research studies in the laboratory, with a focus on determining the early environmental factors that underlie disrupted development of human infants, and the factors that promote resilience. Alma is committed to working with families that typically do not have opportunities to participate in research. She also applies her technical expertise to study visual behavior in infants, to gain an understanding of the relationships between the development of attention, social engagement and cognition.
Sahana Nagabhushan Kalburgi, PhD
Postdoctoral Research Fellow
Primary research projects:
- Healthy baby development and resilience to toxic stress
- Study of Autism Risk in Siblings (StARS)
Sahana Nagabhushan Kalburgi received a PhD in Neuroscience from Vanderbilt University. Her research focuses on the development of scalable biomarkers to aid in early identification of neurodevelopmental disorders. Her ongoing projects aim 1) to characterize the temporal brain network dynamics in healthy infants across the first years of life, 2) to examine differences in brain network dynamics in infants susceptible to early life adversity, and 3) to study brain network dynamics and attentional differences in infants at high risk for autism spectrum disorders. She integrates electroencephalogram (EEG), eye tracking, behavioral assessments, and machine learning methods to study how genetic and environmental factors may play a role in brain development. A long-term goal is to utilize these data for improving outcomes for children at risk for neurodevelopmental challenges, including ASD.
Aimé Ozuna, MPH
Research Assistant
Primary research projects:
- Healthy baby development and resiliency
- California Initiative for Advancing Precision Medicine – Adverse Childhood Experiences Family First Study
Aimé Ozuna received a BA in International Relations and Spanish from University of California, Davis and a Master’s in Public Health from University of Southern California. She has substantial experience working with children and infants in research studies. Aimé’s research interests include infant cognitive and social development and mental health in children and adolescents. She is passionate about ensuring adequate representation for diverse populations in research projects in our laboratory and across CHLA. Aimé plans to attend medical school and specialize in pediatrics or obstetrics/gynecology.
Liam North, BA
Research Assistant
Primary research project:
- California Initiative for Advancing Precision Medicine – Adverse Childhood Experiences Family First Study
Liam North received a BA in Romance Languages and Psychology from New York University. He works on the CIAPM ACEs project, which focuses on developing novel biomarkers of early life stress (ELS) in infants, notably using mitochondrial allostatic load (MAL). His research interests include infant brain development, risk and resiliency, and cultural competency. Liam’s previous research experience focused on mental health in children and adolescents. He plans to attend medical school and specialize in emergency medicine.
Aidee León Lúa
Research Assistant
Primary research project:
- Study of Autism Risk in Siblings (StARS)
Aidee received her BA in Psychology from the University of California, Los Angeles. Her general research interests involve the early identification of autism spectrum disorders (ASD). She is specifically interested in exploring the effects of culture and language in ASD care (screening, diagnosis and intervention), with a particular focus on the experiences of Spanish-speaking Latinx families. She is also interested in improving the accessibility and quality of services for minoritized groups and ensuring that their experiences are considered in research and clinical practices.
Lauren Klein, MS
PhD Student Collaborator, University of Southern California
Primary research project:
- Healthy baby development and resilience to toxic stress CIAPM ACEs Family First Study
Lauren Klein received a Master’s of Science in Computer Science from the University of Southern California and currently is a PhD student in the Interaction Lab in the Computer Science Department at the University of Southern California. Together with her mentor, Professor Maja Mataric, Lauren has been a major collaborator with our laboratory since 2019. Her research focuses on using advanced analytics to model interpersonal social and behavioral coordination during social interaction, including infant-mother interaction, and during human-robot interaction. Her ongoing projects leverage video and audio feature extraction software to support automated, in-depth analysis of interaction data.
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
