Autism Center of Excellence
One of six Autism Centers of Excellence (ACE) in the country has been established at the University of California, San Diego by the National Institutes of Health (NIH), in September 2007. The Center is directed by Eric Courchesne, Ph.D., professor of neurosciences at the UC San Diego School of Medicine. Along with Dr. Courchesne, this Center brings together the expertise of over 40 scientists working collaboratively to discover a bio-behavioral “fingerprint” of what autism looks like in babies at 12-months. In so doing, ACE scientists hope that this information will result in dramatically earlier treatment and a significant reduction in symptoms for affected children.
Autism is a developmental disorder, but the least is known about what is most important: Development. What are the early brain abnormalities? What neural functions do they disrupt? What are the first behavioral indicators of risk for autism? What is the prognosis for the toddler or child at first diagnosis? Which children are likely to respond to known effective treatment and which not? Are there brain or other biological markers that could predict non-responders so that treatment research could be targeted towards discovery of treatments that could help them? What genes and gene pathways are responsible for early brain defects?
The answer to each question posed above comes to the same point: Early identification methods. Early identification, however has eluded the field because autism remains a behaviorally defined disorder and as such, is generally not diagnosed until age 3. This San Diego based ACE, however, will use a novel method called the “1-Year Well-Baby Check-Up Approach” to identify and study 12-month old infants at-risk for ASD, infants at-risk for developmental delay and typical infants using advanced biological and behavioral methods.
Charting the Clinical Profile of Autism from Age 12 to 36 Months
• Implementation of a comprehensive diagnostic, behavioral and clinical testing battery of infants who are at-risk for autism beginning at 12-months. Testing will continue at six-month intervals until each child turns 3 years. Implementation of the One-Year Well-Baby Check Up Approach and Clinical Profiles, led by Karen Pierce
• Evaluation of treatment responsiveness to in-home, 12-month treatment programs. State-of-the-Art Behavioral Treatment, led by Laura Schreibman and Aubyn Stahmer
Discovering Early Developmental Biomarkers of Autism from Age 12 Months
• Structural MRI and function MRI studies of at-risk infants at 12 months and again at 24 months to chart regional brain overgrowth abnormalities and changes in brain function, led by Eric Courchesne, Karen Pierce and Anders Dale
• Autism Biomarkers and Risk Genes: Comparative Gene Expression in Blood, led by Steven Glatt and Ming Tsuang, with the aim of identifying gene expression profiles in circulating blood cells, that can implicate risk genes for this highly heritable disorder
Identification Genes Underlying Brain Overgrowth in Autism
• Identifying genes contributing to brain overgrowth and targeting genetic pathways for brain overgrowth, led by Anthony Wynshaw-Boris, UCSD, and Nicholas Schork of The Scripps Research Institute
• Testing gene susceptibility using neural stem cell models, led by Anthony Wynshaw-Boris, UCSD, and Nicholas Schork of The Scripps Research Institute and Fred Gage of The Salk Institute for Biological Studies and UCSD Department of Neurosciences
Integration Across ACE Projects and Cores: Discovery of the Early Clinical Phenotype, Biomarkers and Susceptibility Genes in Autism
• Utilizing integrated biostatistics and bioinformatics analysis that will enable researchers in all components of the study to share and manage data
• Goal to create a fingerprint of “What is Autism at 12 Months?” by combining clinical, behavioral, brain imaging, and genetic data, led by Nicholas Schork
Eric Courchesne, Ph.D., a Professor of Neurosciences at the University of California, San Diego School of Medicine. He is the overall Director and principle investigator of the UCSD Autism Center of Excellence, and is also the director of the UCSD Autism Center’s MRI Project on early brain development in autism. His efforts have produced new information about the structural, functional and genetic bases of this disorder. Recognized through publications in such journals as Science, the Proceedings of the National Academy of Sciences, The New England Journal of Medicine, Lancet, and the Journal of the American Medical Association (JAMA), his work has significantly contributed to scientists’ understanding of the biological bases of autism, and has been the source of new insights on the functional role of the frontal lobes and cerebellum. He is frequently invited to lecture at major conferences and symposia and has also made numerous media appearances, including as a featured guest on U.S., Canadian, Japanese, French and British public television science programs. His discoveries have also been featured in numerous newspapers and magazines around the world, including Time, Newsweek, The Wall Street Journal and the New York Times, He is a member of numerous advisory boards, including Autism-France and the Autism Society of America.
Karen Pierce, Ph.D., a research faculty member in the Department of Neurosciences at UCSD, is director of the UCSD Autism Center’s fMRI Project on social, emotion and language functioning in the brain in autistic infants and is additionally the director of the Center’s Clinical Phenotype Core that will characterize the clinical features of autism at 12 months of age. Pierce has been involved in both the treatment and neuroscience of autism for the past two decades. She has been awarded several research grants including those from NIMH, the Organization for Autism Research and Cure Autism Now. She has also received an Autism Society of America Research Award and a UCSD Chancellors Research Award in recognition of her work. Pierce has published extensively in a wide range of areas from behavioral treatment to brain dynamics in autism. As director of the Clinical Phenotype Core of the UCSD ACE, Pierce is pivotal in both establishing collaborative relationships with pediatricians in San Diego, as well as ensuring that all babies referred receive thorough diagnostic and psychometric evaluations.
Laura Schreibman, Ph.D., Distinguished Professor of Psychology and Director of the Autism Research Program at UC San Diego, will head up the UCSD Autism Centers’ Treatment Response Core of the Autism Center for Excellence. With more than 30 years’ experience in the behavioral treatment and experimental analysis of autism, Schreibman is one of the world’s leading authorities in the field. She is the author of many books in the field, most recently, “The Science and Fiction of Autism” (Harvard UP, 2005). The Treatment Response Core will provide one year of intensive behavioral modification therapy to children identified as high-risk for developing autism. Beginning when they are 24 months old, the children will receive 15 hours per week of free, state-of-the-art therapy, individualized to the child’s needs and aimed at improving their social, communication and other developmental skills. The children will be assessed again at 36 months, in order to determine who benefited most and if there are physiological correlates that would be helpful in future for identifying the best-fit intervention from the start.
Steven Glatt, Ph.D. is the leader of the UCSD Autism Center’s Gene Expression Project that will identify abnormal levels of genetic activity in infants and toddlers with autism that may be related to abnormal clinical and brain growth and function; abnormal gene expression profiles may signal a risk for autism in infants. He is an assistant professor at the University of Syracuse. Glatt is an expert in psychiatric genetics, especially in the design and analysis of gene expression studies. He has published in Proceedings of the National Academy of Sciences Genomics, the American Journal of Medical Genetics, and Nature Biotechnology.
Anthony Wynshaw-Boris M.D., Ph.D., Professor of Pediatrics and Medicine at the UC San Diego School of Medicine, is the director of the UCSD Autism Center’s Gene Association Project that will identify the genes underlying early brain overgrowth in autism. He is the currently Director of the UCSD Center for Human Genetics and Genomics, and the Vice Chair in the Department of Pediatrics. Wynshaw-Boris is a board certified human geneticist who is a world’s expert on Wnt/PCP, neuronal migration and development, including neurogenesis. He has published in Nature, Cell, Neuron, Molecular and Cellular Biology, Nature Neuroscience, and Nature Genetics. Wynshaw-Boris’ laboratory was the first to describe a mouse model with social behavioral abnormalities, the Dvl1 knock-out mice produced in his lab. This work was published in Cell and was selected as one of the Top 100 science stories by Discover magazine in 1997. Wynshaw-Boris will now apply this expertise toward the analysis of gene pathway disruption in autism.
Nicholas J. Schork, Ph.D. is one of the world’s experts on gene variation and sophisticated statistical methodology to analyze phenotype-genotype interactions, and has published in Science, Genomics, American Journal of Human Genetics, and the Proceedings of the National Academy of Sciences. Schork is the director of the Autism Center’s Bioinformatics and Biostatistics Core and the co-director of the Center’s Gene Association Project. Schork is currently Director of Research at Scripps Genomic Medicine, Professor of Molecular and Experimental Medicine at TSRI and Adjunct Professor of the Center for Human Genetics and Genomics at UCSD. Schork is currently developing methods for analyzing large integrated genomic data sets and his Center Core in collaboration with other Project and Core directors will identify the clinical and biological signatures of autism at 12 months of age.
Fred Gage, Ph.D., one of the co-directors of the Autism Center’s Gene Association Project, is a world-recognized neuroscientist. He is a Professor and Director of the Laboratory of Genetics at the Salk Institute for Biological Studies, and Professor in the Department of Neurosciences at UCSD. Gage is an expert on neural stem cells, as well as the understanding and treatment of some of the most devastating neurological disorders. He has received numerous major national and international honors and prizes for his work, including election to the U.S. National Academy of Sciences and election as President of the Society for Neurosciences. Of relevance to his role in the Center, his laboratory, in a study published in Nature, identified the Wnt pathway as critical for adult hippocampal neurogenesis. In addition, Gage’s laboratory has recently used small molecule libraries to screen for compounds that alter neural stem cell phenotypes.
Anders Dale, Ph.D., founding Co-Director of the Multimodal Imaging Laboratory, an interdisciplinary initiative of the Departments of Neurosciences and Radiology. He is highly skilled in the development and utilization of multimodality imaging technologies. Within both departments, Dr. Dale is the designated point person for integrating the various modes and methods of collecting imaging data, including functional MRI (fMRI), magnetoencephalography (MEG), electroencephalography (EEG), and optical imaging. His efforts are directed in three areas: continuing development and refinement of accurate and automated algorithms for evaluation subjects using multimodality approaches to data collection; statistical analysis of data; and conducting studies in animal models using optical imaging, high field fMRI, and electrophysiological recordings to enhance the interpretation of neuroimaging studies.
Ming Tsuang, M.D., Ph.D. has investigated the genetic and environmental determinants of mental and behavioral disorders for over three decades, including several gene expression studies. Tsuang is currently appointed University Professor, University of California;Distinguished Professor of Psychiatry, and Director, Institute of Behavioral Genomics with the Department of Psychiatry at the University of California, San Diego. He also directs the Harvard Institute of Psychiatric Epidemiology and Genetics in Boston, MA. He received his M.D. degree from National Taiwan University and his Ph.D. and D.Sc. (Doctor of Science) in Psychiatric Epidemiology and Genetics from the University of London. He has been recognized worldwide for his research in schizophrenia, manic-depressive illness, and substance abuse. One of his areas of interest is in the interactions between genetic and environmental risk factors for severe mental disorders. His current effort is to study prevention of psychiatric disorders before their onset, particularly in blood relatives of people suffering from schizophrenia, and to identify traits that predispose a person to developing schizophrenia from both genetic and environmental perspectives. Another area of interest is developing and validating gene-based biomarkers for major mental illnesses, which may ultimately facilitate the development of effective early identification, intervention, and prevention protocols.
Aubyn Stahmer, Ph.D., a research scientist at Rady Children’s Hospital, San Diego and a research faculty member in the Department of Psychology at UCSD, will be co-director of the UCSD Autism Center’s Treatment Response Core. Stahmer has over 15 years of experience treating young children with autism and is the founder and director of Rady Children’s Toddler School, a model inclusive early intervention program. She has published many scholarly articles examining early intervention for young children autism. She currently serves on the board of the California Guidelines for Effective Autism Intervention Committee and is a reviewer for the National Standards in Autism Treatment project due to her expertise in early intervention for this population.