2011 Grantees

Postdoctoral Fellowships

Jill Locke, PhD | University of Pennsylvania

Mentor: David Mandell, ScD

Implementing Evidence-Based Social Skills Interventions in Public School Setting

Several successful social skills interventions for children with autism have been developed for use in school settings. Children who receive these interventions from a research team show marked improvements in friendships and playground behavior, but these gains usually fail to maintain because the school staff do not continue the intervention after the research study ends. In this study, we will modify one of these social skills interventions that was designed for skilled clinicians to use so that it can be used by school aides to improve the social involvement of children with ASD in schools. We then will test the intervention to see whether the intervention is as successful when aides deliver it. Training aides will increase children’s opportunities to practice social skills with their peers at school and increase opportunities for generalization and maintenance of skills, since aides are so frequently present during social periods such as recess and lunch. If successful, this project will provide school districts with a cost-effective, easily implemented, and sustainable program that improves socialization in children with ASD within school settings. Once aides are trained, schools will have a built-in mechanism for continued success that will help many children with ASD and their families address the social challenges associated with ASD.

Portia McCoy, PhD | University of North Carolina

Mentor: Ben Philpot, PhD

Ube3a Requirements for Structural Plasticity of Synapses

Some autism spectrum disorders are caused by the improper expression of a gene termed UBE3A. Having duplications of the UBE3Agene is strongly associated with autism, while deletions of the UBE3A gene cause the severe intellectual disability “Angelman Syndrome”. Both disorders are characterized by cognitive, sensory, and behavioral deficits thought to arise because connections between brain neurons (synapses) form improperly during critical periods of development. However, little is known about how changes in UBE3Aexpression alter the wiring of neurons in the brain. This study aims to determine the role of UBE3A in the structural plasticity of synapses during critical periods of brain development. By filling this gap in knowledge, this study will not only reveal the synaptic structural dysfunction leading to improper circuit formation in UBE3A-related forms of autism, but may also serve as a model to help with therapeutic testing.

Haley Speed, PhD | UT Southwestern University

Mentor: Craig Powell, MD, PhD

Identifying Impairments in Synaptic Connectivity in Mouse Models of ASD

Impaired communication between neurons, or synaptic transmission, is thought to underlie autism-associated behaviors. The goal of this research project is to identify specific deficits in synaptic transmission as novel targets for future therapy. Shank3 is a postsynaptic scaffolding protein required for normal synapse maturation and function, and mutations and copy number variations in the Shank3 gene have been directly implicated in heritable autism with mental retardation in humans. Our laboratory will use genetic mouse models of autism containing regional deletions of the Shank3 gene to 1) Understand how the structure and function of hippocampal synapses are impaired by region-specific mutations in the Shank3 gene, and 2) Determine if each mutation contributes to autism-associated deficits in learning and memory. This thorough, interdisciplinary strategy will identify subcellular mechanisms that will immediately translate into pre-clinical studies for treatment of autism-associated behavioral deficits.

Elena Tenenbaum, PhD | Women & Infants Hospital at Brown University

Mentor: Stephen Sheinkopf, PhD

Attentional Distribution and Word Learning in Children with Autism

This study will investigate how children with autism attend to information when learning new words and how that attention might affect their language development. We know from previous research that children with autism tend to look at social scenes differently than their typically developing peers. Recent research with typically developing children suggests that the way a child looks at social scenes can predict successful language development. To explore the possibility that attention to social scenes among autistic children might be affecting their language development, we will conduct an eye tracking study of visual attention in a word learning task. Children will watch videos of a person labeling new objects while we track their attention to the scene. We will then test the child’s recognition of the newly learned words and compare their success to their patterns of attention to the word learning scenes. We will also investigate whether their ability to learn new words in the lab relates to their language development outside of the lab. It is our hope that the information we obtain in this study will lead to the development of new interventions for facilitating language learning in children with autism.

Predoctoral Fellowships

Jessica Bradshaw | University of California at Santa Barbara

Mentor: Robert Koegel, PhD

Prelinguistic Symptoms of Autism Spectrum Disorders in Infancy

This research project aims to enhance the understanding of prelinguistic symptoms of autism spectrum disorder in infants less than 12 months of age through the assessment of preverbal social and communication behaviors in the context of a pilot treatment program. Infants between 9-12 months of age exhibiting signs of ASD will be enrolled in a pilot treatment program designed to increase social engagement and decrease overall symptomology. This intervention will be a modified version of Pivotal Response Training, a validated manualized naturalistic intervention utilizing developmental and applied behavior analysis approaches. A parent-education component will also be incorporated allowing for families of infants at risk for ASD to better understand autism and learn effective therapeutic techniques. Despite research showing early signs of ASD in infancy, intervention resources for infants exhibiting early symptoms remain limited. This study aims to address this gap by assessing social-communicative gains made subsequent to the implementation of a comprehensive treatment program.

Christie Buchovecky | Baylor College of Medicine

Mentor: Monica Justice, PhD

Identifying Genetic Modifiers of Rett Syndrome in the Mouse

Rett Syndrome is an autism-related disorder that affects primarily girls and has a prevalence of 1 in 10,000 births. Restoring function of the gene responsible for Rett Syndrome, Mecp2, to mutant mice allows them to live normal, healthy lives, even after symptoms have developed. This is hopeful news for patients, highlighting a potential for reversing the disease by pharmacologic means. Unfortunately, Mecp2 is not a promising drug target, as a genetic trick that would be impossible in humans is required to restore function in mice. Our lab has undertaken a genetic screen in which we randomly mutated a second genomic site in Mecp2-mutant mice to locate more pharmacologically targetable genes. From this screen, we have identified five lines carrying inherited suppressors that increase lifespan and decrease other Rett Syndrome related symptoms in Mecp2-mutant mice. This project focuses on characterizing the two mutations present in the line that show the greatest degree of rescue – one of which, we believe, provides great therapeutic promise. In the process of assessing the degree of rescue for each line, we will evaluate the brain structures altered in Rett Syndrome to determine the degree to which neuronal maturation deficits are rescued. Furthermore, we will use established mouse behavior tests to assess the extent to which the suppressors alter cognitive ability and motor function. Understanding the suppressors at a functional molecular level may provide an avenue for development of therapeutic compounds applicable to multiple types of autism spectrum disorders.