Developmental, Genetic and Molecular Neurobiology

The Child Study Center has a number of active basic science laboratories that are dedicated to applying genetic and molecular techniques to the study of neuropsychiatric and development disorders of childhood. The laboratories have active research programs in a number of disorders including autism, Tourette’s syndrome, OCD, learning disabilities, speech and language disorders and learning and memory. Examples of some of the projects and techniques used are listed below.

Animal Models

Mice that carry gene mutations are challenged with environmental stimuli to understand how genes and environmental events interact during development.

• Role of growth factors in brain development and recovery after perinatal hypoxic insults.
• Cellular and synaptic plasticity after enriched sensory and cognitive experience.
• Role of tyrosine phosphorylation and dephosphorylation in synaptic plasticity and cognitive function.
• Role of genes and epigenetic events on the postnatal development of brain inhibitory systems.

Regulation of neural stem cells during development

Fibroblast Growth Factors (FGF) are required for the differentiation of neural stem cells into neurons. These growth factors continue to be required throughout development for brain growth, neuronal differentiation and survival. Animals lacking specific FGF receptors are hyperactive and cognitively impaired. These animal models will allow us to understand the derangements in brain development that underlie Tourette’s, ADHD and other developmental disorders.

Regulation of synaptic function by protein tyrosine phosphatases

The tyrosine phosphatase, STEP, regulates the activity of key signaling proteins involved in the development of synaptic plasticity. How this occurs and the structure and function of STEP is one of the main focuses of the laboratory. The role of STEP in learning and memory is an active area of study.

Human Genetics

Faculty members at the Child Study Center lead a wide range of human genetic studies investigating the etiology and pathogenesis of autism, Tourette’s syndrome, speech and language disorders and learning disabilities and mental retardation. Current areas of interest include:

• Molecular cytogenetic, array based cytogenetic and deep re-sequencing studies of childhood developmental neuropsychiatric disorders;
• Studies of consanguineous families and genetic isolates focusing on Tourette’s syndrome, autism, mental retardation and learning disabilities and language disorders;
• Genome wide studies of CNS vascular, psychiatric and developmental disorders using both association and copy number variation strategies;
• Candidate gene association strategies including an investigation of the role of genes in the FGF pathway in autism Spectrum Disorders; and
• Genetic and Epidemiological studies of autism and Tourette’s syndrome in South Korea.
• Studies of correlations between genetic polymorphisms in GABA-related genes and GABA concentration in the human brain.
• Studies of gene-gene and gene-environmental interactions in case-control cohorts.
• How genetic variability interact with the environment to affect parenting thoughts and behaviors.

Neuropharmacology/Neurochemistry

Faculty are involved in pre-clinical psychopharmacology research, including studies on basic mechanisms of action of serotonergic agents in non-human primates and studies assessing bioeffect in treatment studies of autism and other pervasive developmental disorders. Studies examining neurochemical and neuroendocrine measures in autism, Tourette’s syndrome, attention deficit/hyperactivity disorder, depression, trauma and addiction as well as in a range of parent groups are conducted in parallel with genetic analyses.

Postmortem human studies

Morphometric and cellular studies using unbiased stereological techniques are used to investigate the cells and neuronal systems that may underlie the symptoms of Tourette’s syndrome. These studies compare human brain tissue from patients who donated their brain for research and normal controls.

Courses

A number of courses are taught by the faculty. These include: “Neurodevelopment and Neuropsychiatric Disorders”, “Genetic Sciences for Developmentalists”, and others. These courses focus on connections between the genome and neuropsychiatric disorders, such as the progressive specialization of cellular function within the CNS, with emphasis on the relationships between evolutionary conserved genes and signaling systems and neuropsychiatric disorders such as depression, autism and schizophrenia, and the role of environments and genes in the development of complex behavioral phenotypes. [link to syllabus]

Journal Club in Developmental Neuroscience

Once a month, this Journal Club discusses recent advances in neuroscience research. We meet in the Senn Conference Room, Child Study Center, SHM I-273. For more information, email: flora.vaccarino@yale.edu.

Faculty

George Anderson, Ph.D.
Elena Grigorenko, Ph.D.
Young Shin Kim, MD, PhD [link]
James Leckman, M.D. [link to TS research]
Paul Lombroso, M.D.
Matthew State, M.D., Ph.D.
James Swain, M.D., Ph.D.
Flora Vaccarino. M.D.

Labs and Programs

• Dr. Matthew State co-directs the Yale Program on Neurogenetics [link to website], along with Dr. Murat Gunel, Chief of Vascular Neurosurgery. This program brings together faculty from the Departments of Genetics, Neurobiology, Neurosurgery, Molecular Biophysics and Biochemistry and Internal Medicine, along with CSC faculty, to identify genes and elaborate molecular mechanisms involved in both structural and functional disorders of the Central Nervous System.
• Dr. Lombroso directs the Laboratory of Molecular Neurobiology
• Dr. Vaccarino directs the Laboratory of Developmental Neurobiology
• Dr. Grigorenko directs the Laboratory of Behavioral and Molecular Genetics
• Dr. Anderson directs the Laboratory of Developmental Neurochemistry and the Core Resource Laboratory of the Yale Interdisciplinary Research Consortium on Stress, Self Control and Addiction
• Dr. Swain directs the Risk Resilience and Recovery brain imaging lab studying the brain basis, genetics and neurochemistry of human parenting toward optimizing infant outcomes