University of Southern California (USC), Los Angeles, CA
Clara M. Lajonchere, Ph.D.
Dr. Lajonchere, Research Assistant Professor at USC’s Viterbi School of Engineering and Clinical Assistant Professor of Pediatrics at USC’s Keck School of Medicine, serves as Principal Investigator and Director of the Center.
Dr. Lajonchere has worked in the field of psychiatric genetics for the last 15 years and has served numerous multi-site studies in many different capacities. Her broad background in basic science and applied clinical research makes her exceptionally well suited to provide leadership for the Center.
As the Director of Clinical Research for Cure Autism Now, a national autism non-profit organization focused on accelerating the pace of autism research, Dr. Lajonchere oversees three national multi-site research programs that include the Autism
Treatment Network (ATN), Clinical Trials Network (CTN), and the Autism Genetic Resource Exchange (AGRE). Dr. Lajonchere has played a critical role in the development of the ATN, a network of treatment and research centers dedicated to improving medical care for children and adolescents with autism. The ATN was created to establish standards of multidisciplinary care based on research and shared clinical practice. Her portfolio has grown to include leadership and oversight of the CTN, established to conduct multi-center clinical trials in autism to test the efficacy of existing treatment approaches as well as rapidly screen new promising compounds that emerge from biomedical research. Both of these programs serve to strengthen translation research in academic health centers. The AGRE program, established by Cure Autism Now in 1997, represents the world’s largest private collection of genotypic and phenotypic data for autism research. Under her leadership and direction, AGRE has become a driving force in autism research, with a collection that has grown to include over 1,500 multiplex families, attracted 156 researchers nationwide, and generated 87 peer-reviewed publications.
Dr. Lajonchere has established partnerships with leading autism researchers to increase the depth and breadth of the resource across a diversity of disciplines including human genetics, molecular biology, neuroimaging, neuroscience, and psychology. Dr. Lajonchere has been working collaboratively with researchers in Europe and Latin America to establish the AGRE model in France, Venezuela, and Mexico. Over the last two years, she has been working closely with program staff at the National Institutes of Health (NIH) to develop bioinformatics tools for autism research and currently serves as a national advisor for NIH’s National Database for Autism Research.
Dr. Lajonchere supervises recruitment and characterization of participants with autism and related conditions, ensures the obtainment of ascertainment milestones, oversees the application of high-throughput phenomic battery, works collaboratively to develop phenotype selection algorithms, contributes to the development of secure and confidential data management systems, facilitates usage of clinical and experimental procedures in new ways with a view to extend their clinical and theoretical usefulness and ensures adherence to a core phenotype characterization battery. Dr. Lajonchere also ensures close communication and collaboration among Center investigators on all aspects of phenomic characterization.
Steven O. Moldin, Ph.D.
Dr. Steven Moldin, Research Professor of Psychiatry and the Behavioral Sciences at USC’s Keck School of Medicine and Executive Director of the Washington, DC Office for Research Advancement in USC’s Office of the Provost, is Co-Director of the Center for Genomic and Phenomic Studies in Autism.
He assists the Center Director, Dr. Clara M. Lajonchere, and the other Center Co-Director, Dr. David Amaral, in the supervision, coordination and oversight of all Center activities.
For 11 years until joining USC in March, 2006, Dr. Moldin was a senior NIH program official who developed and initiated numerous workshops, Requests for Applications and Program Announcements to support genetic and neuroscience initiatives on autism. While at the National Institute of Mental Health, he developed long-term strategic plans and a scientific vision for neurobiological research on autism, autism spectrum disorders, Rett Syndrome, and Fragile X syndrome. His considerable programmatic experience in autism spanned multiple disciplines – e.g., phenomics, molecular and cellular neuroscience, molecular biology, clinical neuroscience, child neurology, pharmacology, and human genetics – and he played a critical role in developing and supporting state-of-the-art multidisciplinary scientific collaborations. He also developed long-term strategic plans and scientific vision for translational neuroscience, in which genetic and neurobiological research shaped the development of models for mental disorders in the mouse and other experimental systems. In addition to editing a special issue of Genes, Brain and Behavior on autism and a commentary in J Neuroscience (see Appendix), he has co-edited with John Rubenstein the book, Understanding Autism: From Basic Neuroscience to Treatment.
For nine years, Dr. Moldin was program officer for the NIMH Human Genetics Initiative
(http://zork.wustl.edu/nimh/NIMH_initiative/NIMH_initiative_link.html) – a broad and multifaceted human genetics initiative to collect sets of families with probands and relatives affected with mental disorders – and program officer for the NIMH Center for Collaborative Genetic Studies on Mental Disorders (http://zork.wustl.edu/nimh/). The primary goal of the Center was to serve as a centralized scientific community resource that distributed DNA extracted from immortalized cell lines and phenotypic information for use in genetic studies of autism and other mental disorders. Dr. Moldin oversaw the distribution of comprehensive phenotypic and genotypic information, as well as DNA and lymphoblast cell lines, to over 200 investigative teams worldwide. While at NIH, he also developed long-term strategic plans and a scientific vision for the creation and distribution of centralized community resources for human genetic studies on autism and other mental disorders. He also oversaw neuromice.org (http://www.neuromice.org), a trans-NIH centralized resource that provided to the scientific community murine resources for use in genetic studies. In all of these activities, Dr. Moldin worked to ensure rapid and efficient access to research resources by the scientific community. Overall, his considerable experience in coordinating and overseeing state-of-the-art multidisciplinary centralized resources for genetic studies on autism make him uniquely suited to be a Co- Director of this Center.
Constantinos Sioutas, ScD.
Dr. Constantinos Sioutas is Professor of Civil and Environmental Engineering at USC. He helps train the field measurement team to set up air quality sampling equipment; assures the timeliness of the tasks and data collection related to the study of air quality and airborne environmental risks; coordinates with the Center director and co-directors to ensure completion of tasks for studies on air quality and airborne environmental risks; coordinates conference calls and meetings to review progress and plan analyses of air quality and airborne environmental risk data and presentation of results; prepares major presentations, reports and publications of results from analyses of air quality and airborne environmental risks; and supervises a research assistant (USC doctorial student) in the field experiments, QA/QC of all air quality and airborne environmental risk data, and works on final data analysis and the preparation of manuscripts to be submitted for publication.
Autism Genetic Resource Exchange (AGRE), Los Angeles, CA
Janet Miller, J.D., Ph.D.
Dr. Janet Miller is AGRE’s Clinical Director. As a clinical psychologist and attorney, Dr. Miller is uniquely qualified to address clinical and diagnostic issues as well as oversee contractual and regulatory matters.
Prior to working for AGRE, Dr. Miller worked as the project coordinator of the IMGSAC genetic study at UCLA’s Neuropsychiatric Institute. She leads workshops on the Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule (ADOS) and is extremely well-versed in the diagnosis of children and adolescents with autism. Dr. Miller is a certified ADI-R and ADOS trainer who works closely with the author of the instruments, Dr. Catherine Lord. She oversees phenotypic data quality, including maintenance of clinician reliability on diagnostic assessments, through review of videotapes and periodic on-site supervision, as well as working with the database team to develop data QA/QC protocols. She also conducts on-going case conferences with the AGRE clinical team to confirm consensus diagnoses of affected subjects along the autism spectrum. Dr. Miller oversees all aspects of deliverables, ensuring that: a) research goals are met in a timely manner with scientific integrity; b) work is completed within budgeted amounts; c) work is in complete compliance with all state and federal regulations; and d) high-through phenomics activities and data collection remains on schedule with continued attention to minority recruitment.
Dr. Miller works collaboratively with the Center Director and co-Directors and Drs. Catherine Lord, Sally Rogers, Geraldine Dawson and Annette Estes on clinical and diagnostic issues and implementation of phenotype selection algorithms. She works closely with Drs. Irva Hertz-Piccioto and Deborah Bennett from the MIND Institute/UC-Davis on the development and implementation of environmental survey tools that will be utilized by AGRE staff in their nationwide assessment of autism families. Dr. Miller also works closely with the Database Manager to ensure that data collection standards are met.
MIND Institute/University of California (UC) – Davis, Davis, CA
David G. Amaral, Ph.D.
Dr. David Amaral is Professor in the Department of Psychiatry and Behavioral Sciences (School of Medicine). Dr. Amaral is a neuroscientist with expertise in neuroanatomical and behavioral studies of functions ranging from memory to social behavior to emotion. Much of this work has been carried out in the nonhuman primate. However, since 2001, Dr. Amaral has also been conducting human studies to define the neuropathology of autism. Dr. Amaral was a founding member of the MIND Institute/UC-Davis and has been the Research Director since 1998.
Dr. Amaral serves as Center Co-Director, working closely with Dr. Lajonchere, the Center Director and Dr. Steven Moldin, the Center Co-Director. He provides general scientific management of the project.
Dr. Amaral ensures that timely progress is made, that data are integrated across disciplines and that Center research results are published in a timely fashion. Dr. Amaral also participates in the neuroimaging component of the phenotyping effort.
Sally J. Rogers, Ph.D.
Dr. Sally Rogers is a Professor in the Department of Psychiatry and Behavioral Sciences (School of Medicine) and a developmental psychologist at the MIND Institute/UC-Davis. Dr. Rogers does both research and clinical work at the MIND Institute. Dr. Rogers studies early social, cognitive, and emotional development; development of motor skills, communication, imitation, and language in children with severe disabilities; development of social relationships in people with disabilities; and treatment efficacy in autism. Her clinical interests include early diagnosis and intervention for children with autism spectrum disorders, and evaluation of cognitive, behavioral, social, emotional and adaptive functioning in children with other developmental disorders.
As leader of the behavior subgroup, Dr. Rogers is responsible for all aspects of the behavior sub-project, including data analysis and quality of the behavior data. Dr. Rogers works collaboratively with the Center Director and co-Directors and Drs. Catherine Lord, Janet Miller, Geraldine Dawson and Annette Estes on clinical and diagnostic issues and implementation of phenotype selection algorithms.
Robin Hansen, Ph.D.
Dr. Robin Hansen is the Director of Clinical Programs at the MIND Institute/UC-Davis and Professor and Chief of Developmental-Behavioral Pediatrics, Department of Pediatrics. Dr. Hansen is a developmental behavioral pediatrician/researcher with experience in treating children with neurodevelopmental problems such as pervasive developmental disorder, autism, learning disorders, and attention deficits. She heads a multidisciplinary clinic that diagnoses children, plans and initiates intervention strategies, and works closely with patient families. Her clinical research has focused on children’s temperament and its effects on parenting, long-term effects of prenatal drug exposure, and etiologic diagnosis of pervasive gene-environment interaction. She is responsible for oversight of the clinical assessments completed as part of the Childhood Autism Risks from Genetics and Environment (CHARGE) epidemiologic study at UC-Davis. Dr. Hansen has developed services for families affected by parental substance abuse, infant mental health, and children in foster care in Sacramento County.
As Medical Leader, Dr. Hansen provides oversight of the acquisition and reliability of medical data collected by medical staff.
Tony J. Simon, Ph.D.
Dr. Tony Simon is a cognitive neuroscientist who moved to the MIND Institute/UC-Davis from the Children’s Hospital of Philadelphia in 2005. Dr. Simon was charged with developing a child-friendly environment at the UC Davis Imaging Research Center while extending his independent research program. Several important changes have already been made that address a range of issues relating to the acclimation of children to the imaging environment and the acquisition of pediatric data. He continues to advance further such changes, as well as developments specifically related to the improvement of analytical methods for pediatric data.
Moreover, Dr. Simon has been implementing imaging protocols such as diffusion tensor imaging (DTI) and arterial spin labeling that have not typically been used with pediatric populations. He has been conducting both structural and functional MRI studies in children with a variety of neurodevelopmental disorders (particularly chromosome 22q11.2 deletion syndrome) since 2001.
Dr. Simon oversees the development and application of techniques for whole brain volumetric analyses, including those that address registration and normalizationof pediatric brains to appropriate templates. He also analyzes connectivity, mainly from diffusion tensor data using both quantitative and qualitative fiber tracking methods. These analyses direct the search for identifying robust autism endophenotypes.
Cliff Saron, Ph.D.
Dr. Cliff Saron is Chief of Human Electrophysiology at the Center for Mind and Brain, UC
Davis. Dr. Saron’s research centers on using high-density event-related potentials to investigate sensorimotor integration using simple visual and motor tasks. He is also interested in the role of attention in these tasks and the relatively unexplored domain of multisensory integration, particularly the interplay of auditory and visual processing streams in the presence of either concordant or discordant inputs.
Dr. Saron oversees the collection, analysis and interpretation of event-related potential data on children with autism, in pilot study to identify a robust autism endophenotype.
Irva Hertz-Picciotto, Ph.D
Dr. Irva Hertz-Picciotto is Professor of Epidemiology in the Department of Public Health Sciences, Division of Epidemiology, and Chief, Division of Environmental and Occupational Health. Dr. Hertz-Picciotto’s research concerns the impact on health of a variety of environmental chemicals, including lead, arsenic, pesticides, PAHs and PCBs. She has published widely on reproductive and perinatal health, design and analytic methods for epidemiologic data, especially pregnancy outcome studies, and assessment of risk from environmental factors. She is the Principal Investigator of the CHARGE (Childhood Autism Risks from Genetics and the Environment) Study and Deputy Director of the NIH-funded Center for Children’s Environmental Health. She is president of the Society for Epidemiologic Research, served previously as president of the International Society for Environmental Epidemiology, and chaired the Institute of
Medicine/National Academy of Sciences 2000 and 2002 Committees to Review Health Effects in VietnamVeterans of Exposure to Herbicides.
Dr. Hertz-Picciotto directs all aspects of the MIND Institute/UC-Davis environmental study, and has responsibility for supervision of staff, maintenance of data quality and confidentiality, and preparation of reports and profiles. Dr. Hertz-Piccioto also works closely with the Center Director on the development and implementation of environmental survey tools that will be utilized by AGRE staff in their nationwide assessment of autism families.
Frank R. Sharp, M.D.
Dr. Frank Sharp is a Professor of Neurology and a member of the MIND Institute/UC-Davis who is a trained clinical neurologist and neuroscientist. His laboratory focuses on molecular neurobiology, genomics, neural cell injury and cell death and the blood genomics of neurological disease. Scientifically, he was among the first to describe the use of the immediate early gene c-fos to map active neurons in the brain. His group was the first to describe the neuroprotective properties of heat shock proteins in ischemic and other types of brain injury. His group provided the first proof of principle that changes in gene expression in the blood using microarrays can be used to assess injury and disease in the brain. This has included rodent studies with stroke and hypoglycemia models, and it has included human studies of Tourette syndrome and elephant man’s disease.
Dr. Sharp serves as the leader for the Genomics sub-project. Dr. Sharp supervises the collection of RNA and DNA during the course of the studies, the processing and quality assessment of both, and the analyses of the genomic data to identify robust endophenotypes for autism.
Judy Van de Water, Ph.D.
Dr. Judy Van de Water is a Professor in the Division of Rheumatology, Allergy and Clinical
Immunology and is a member of the MIND Institute/UC-Davis. Dr. Van de Water’s primary interests for the past 15 years include autoimmunity, immunopathology, and molecular and cell biology. Her diverse research interests include primary biliary cirrhosis and the immunobiology of autism. Dr. Van de Water is also investigating potential environmental risk factors contributing to the incidence and severity of childhood autism.
Dr. Van de Water serves as the leader of the immunology sub-project and oversees the collection of immunology data, including the analysis of data and creation of immune profiles to identify potential autism endophenotypes.
Keith Widaman, Ph.D.
Dr. Keith Widaman is a professor and chair of the Department of Psychology. He conducts research on the development of human mental abilities and on statistical methods used in the social sciences. In research on mental abilities, Dr. Widaman has studied the cognitive processes underlying numerical facility, especially as these processes change in nature and in speed of execution from childhood through early adulthood. He also studies the structure and development of adaptive behaviors of persons with mental retardation, particularly how parenting behaviors foster growth of adaptive behaviors. His quantitative work encompasses contributions to factor analysis, structural equation modeling, and item response theory, and he is currently working on reformulating the role of significance testing in regression analysis. Dr. Widaman is a Fellow of the American Psychological Association, won the Cattell Award from the Society of Multivariate Experimental Psychology, and is on the editorial boards of seven journals, including Psychological Methods, Multivariate Behavioral Research, and Intelligence.
Dr. Keith Widaman oversees the design and data analysis of studies for the MIND Institute/UC-Davis. He works closely with Dr. Kustanovich from AGRE and ensures that all phenomic data collected in the MIND Institute/UC-Davis are integrated into the AGRE database. He also ensures that all data and biomaterials collected by the MIND Institute/UCDavis are efficiently transmitted to the National Database for Autism Research and to the NIMH Human Genetics Initiative.
Lee-Way Jin, M.D., Ph.D.
Dr. Lee-Way Jin is an Associate Professor in the Department of Pathology and Laboratory Medicine and a member of the MIND Institute/UC-Davis. Dr Jin is a neuropathologist with 15 years of experience. His current research focuses primarily on the contribution of glial cell abnormalities to autism spectrum disorders and neurotoxocity due to amyloid-protein in Alzheimer’s disease.
Dr. Jin is responsible for overseeing the cataloguing and tracking of blood samples collected by the MIND Institute/UC-Davis, and he ensures that these samples are transferred to AGRE and to RUCDR (which establishes and maintains resources for the NIMH Human Genetics Initiative).
University of Michigan, Ann Arbor, MI
Catherine Lord, Ph.D.
Dr. Catherine Lord, the foremost expert on autism-related diagnostic procedures and senior author of the ADI-R and ADOSG, lends her expertise to a full range of methodological issues associated with the collection of data by the Center. This role is facilitated by the fact that Dr. Lord was involved in the early creation of the diagnostic battery for the AGRE program. She and Dr. Janet Miller, AGRE Clinical Director who is a certified ADI-R and ADOS trainer, discuss strategies for improved diagnostic evaluation, data cleaning and reliability for the program.
Dr. Lord works collaboratively with the Center Director and co-Directors and Drs. Miller, Sally Rogers, Geraldine Dawson and Annette Estes on clinical and diagnostic issues and implementation of phenotype selection algorithms. Dr. Lord also works with Center investigators to analyze data generated from Center pilot studies involving 3D craniofacial morphology, structural brain imaging, DNA microarrays, immunological assays, auditory evoked potentials, psychophysiology, and air quality assessments. A specific goal is to extract multidimensional endophenotypes. She also consults on the enhancement of the high throughput phenomics battery used by the Center, to ensure that it generates a comprehensive, state-of-the-art catalog of phenotypes. Dr. Lord works with the Center Investigators to extract multidimensional endophenotypes for autism that can be incorporated in future genetic studies.
Childrens Hospital Los Angeles (CHLA), Los Angeles, CA
Mark Urata, M.D., D.D.S.
Dr. Mark Urata, an expert on craniofacial development and abnormalities, works collaboratively with Dr. Curtis Deutsch from the E.K. Shriver Center/University of Massachusetts Medical Scool and the Center Director, Dr. Lajonchere, to establish a state-of-the-art quantitative dysmorphology research clinic within the Department of Craniofacial Surgery at Chilldrens Hospital Los Angeles (CLHA). This new clinic will make use of existing infrastructure: space has been provided by the General Clnical Research Center (GCRC) at CHLA. The quantitative data derived from these assessments will be examined in a pilot study of autistic children ascertained by AGRE in California to identify autism endophenotypes based on craniofacial dysmorphology.
Dr. Urata works closely with Dr. Deutsch to establish at CHLA all equipment, software, protocols and procedures necessary for 3D scanning of the craniofacial surface using a cutting edge 3dMD craniofacial scanner and the necessary software to permit rapid and quantative assessments of craniofacial dysmorphology. Dr. Urata assures high test-retest reliability for quantitative dysmorphology assessments in the CHLA clinic, and closely supervises the Workstation Operator to ensure proper assignment of anthropometric landmarks and on-line measurement of linear distances and arcs connecting these landmarks.
Dr. Urata works with Dr. Deutsch to implement in the CHLA clinic an anthropometric protocol (developed by Deutsch and Farkas) that lists operational definitions of the anomalies based on these anthropometric measures. Dr. Urata ensures that: a) recruitment goals are met in a timely manner, and with scientific integrity; b) the cost of quantitative dysmorphology assessments are within budgeted amounts; c) work is in complete compliance with all state and federal regulations; d) data collection remains on schedule with continued attention to minority recruitment; e) and that data are collected and managed properly. Dr. Urata also works closely with Dr. Kustanovich from AGRE and ensures that all ‘raw’ dysmorphology data collected and analyzed at the E.K. Shriver Center are integrated into the AGRE database. He also ensures that all these data are efficiently transmitted to the National Database for Autism Research and to the NIMH Human Genetics Initiative.
E.K. Shriver Center/University of Massachusetts Medical School, Waltham, MA
Curtis K. Deutsch Ph.D.
Dr. Curtis Deutsch is an expert on the quantitative assessment of craniofacial development and morphology and reviews all quantitative and clinical morphometry assessments conducted for the Center at Childrens Hospital Los Angeles (CHLA).
He works closely with the Center Director (Dr. Lajonchere) and Dr. Mark Urata and he: (1) trains the CHLA Workstation Operator to use a cutting edge 3dMD craniofacial scanner and all necessary software to permit rapid and quantative assessments of craniofacial dysmorphology; (2) trains the CHLA Workstation Operator to use a standardized 3dMD image capture protocol, and an anthropometric protocol (developed by Deutsch and Farkas) that lists operational definitions of the anomalies based onanthropometric measures determined by the scanner; (3) establishes interrater reliability with the Workstation Operator prior to undertaking measurements for the study, and maintain interrater reliability at six-month increments; (4) computes 3D morphometry based on projective geometry routines; (5) confers with Dr. Lewis Holmes on the identification of known genetic and other syndromes that would rule out autism; (6) consults with Dr. Holmes on the identification of putative subtypes of autism syndromes on the basis of clinical and quantitative findings; (7) performs cluster analyses to identify these putative autism subtypes in a systematic way, based on characteristic quantitative craniofacial anomalies; (9) computes full-scale and embryologically-derived anomaly combinations scores to serve as quantitative endophenotypes; (9) characterizes quantitative dysmorphology characteristics that may be robust autism endophenotypes and serve as a marker of underlying neurodevelopmental pathways; (10) performs statistical analyses of group contrasts; (11) coordinates with the Database Manager to document specific anomalies within quantitative morphometry protocols, that is in turn provided to Dr. Urata at CHLA; (12) collaborates with Center investigators in the use of quantitative dysmorphology measures with other measures to define multidimensional endophenotypes; (13) writes progress reports;(14) works closely with Dr. Kustanovich from AGRE and ensure that all ‘raw’ dysmorphology data generated at CHLA and all quantitative assessments of that data generated and reviewed at the E.K. Shriver Center are integrated into the AGRE database. He also ensures that all these data are efficiently transmitted to the National Database for Autism Research and to the NIMH Human Genetics Initiative; and (15) collaborates with the Center Director and Co-Director in writing manuscripts and final reports.