2022 Grantees

Predoctoral Fellowships

Viktoria Haghani | University of California at Davis

Mentor: Janine LaSalle, Ph.D.
Advisor: Ian Korf, Ph.D.

Clarifying the Role of the MeCP2 Gene in the Timing of Symptom Progression in Rett Syndrome

Rett Syndrome is caused by a mutation on the X chromosome at MeCP2. Girls with Rett Syndrome share many features of autism, including delayed or lack of language development, impaired fine motor skills, repetitive behaviors and cognitive disability. MeCP2 activity is also regulated by environmental factors and has been implicated in autism when a genetic cause has not been identified. This fellow will look closely at changes in MeCP2 binding and how it regulates gene expression by isolating different types of neurons at different ages to determine which are critical in the progression of symptoms. The fellow will also employ a sophisticated analysis of machine learning techniques to integrate the data to predict how MeCP2 activity regulates different neuron types at different points in development. This will allow scientists to move closer to providing patients with targeted approaches to interventions.

Rett Syndrome Research Trust is partnering with ASF to provide funding for this grant.

Emily Isenstein | University of Rochester

Mentor: John Foxe, Ph.D.
Advisor: Duje Tadin, Ph.D.

Understanding Hyper-Responsiveness to Touch in the Autistic Brain

Oversensitivity to touch is common in autism and can lead to discomfort and harm. In some cases, people with autism avoid other people’s touch but seek out tactile stimulation through self- stimulatory behaviors. Self-stimulation can be anything from finger tapping to headbanging, which is harmful and dangerous. While the differences in the brain’s response to different types of touch have been studied in neurotypical people, there is little information on the different responses in people with autism. This fellow will examine how the autistic brain responds to different types of touch, ultimately providing a biological basis for determining why some touch is avoided while some is sought out, which could improve therapy for dangerous self-stimulatory behaviors.

Stephen Pastore | University of Toronto

Mentor: John Vincent, Ph.D.
Advisor: Karun Singh, Ph.D.

Novel Methods to Understand the Function of Autism Risk Gene PTCHD1

Recent research has implicated the gene PTCHD1 on the X chromosome as contributing to the causes of autism and intellectual disability, but there is still very little known about what it does and how it leads to changes in the brain. This project will be the first-ever attempt to determine the function of the PTCHD1 protein in its natural biological setting. Cells will be manipulated to create mutations in PTCHD1, then turned into neurons, and then the proteins that are expressed will be measured. Finally, the fellow will measure how these proteins interact in the brain. This will enhance our understanding of how this gene interacts with the rest of the brain and expand the range of therapeutic approaches intended to target specific types of dysfunction in people with autism.

April Pruitt | Yale University

Mentor: Kristen Brennand, Ph.D.
Advisor: Ellen Hoffman, M.D., Ph.D.

Estrogen Exposure in Early Development as a Factor in ASD Sex Bias

Autism has a well-established and prominent 4:1 male: female bias in diagnosis, but the biological basis for this difference remains unknown. One possible theory is that the presence of estrogen may play a role in the activity of brain cells that turn neurons on or off, which is part of the “excitation/inhibition” theory in autism. To test this theory, this fellow will create different types of neurons using induced pluripotent stem cells from both males and females with autism, with and without a rare genetic variation in an autism gene called neurexin. Then, estrogen will be applied to these cells and gene expression and functioning of different cell types will be compared. This gene-by-environment study will help identify the role of estrogen during development as a component in the later biological and behavioral features of females compared to males with autism.

Nicole Rosen | University of California at Los Angeles

Mentor: Catherine Lord, Ph.D.
Advisor: Marsha Mailick, Ph.D.

Sibling Influence on Adaptive Behavior in Individuals with ASD

Siblings have the potential to shape the developmental trajectories of individuals with autism. Early studies have shown the positive impact that a sibling can have on the outcome of an autistic brother or sister. However, these studies were unable to identify which particular aspects of being a sibling contribute most to this effect. This study will leverage existing data from about 5,000 families across multiple longitudinal studies to understand the role of a sibling in longer-term adaptive behavior, and to better identify specific factors that may influence this benefit. Findings from this research may inform intervention planning to maximize adaptive skill development across time and optimize outcomes in those with autism. The results may also provide important insight into the needs of undiagnosed siblings who may themselves need support.

Simona Sarafinovska | Washington University School of Medicine

Mentor: Joseph Dougherty, Ph.D.
Advisor: John Constantino, M.D.

Molecular and Cellular Origins of Sex-Specific Social Motivation Deficits in Autism

More and more evidence is pointing to sex-related differences in gene expression as a potential explanation of the male sex bias in autism diagnosis. This study will examine the role of a gene called MYT1L that has been linked to autism. Mouse models will examine the expression of this gene in the cortex (where there is no evidence of a sex difference in expression of MYT1L) and compare it to expression in the hypothalamus (where there are sex-specific differences linked to social behaviors). The fellow will also examine social learning in males and females and count neurons to look for both behavioral and cellular changes. This will determine where in the brain sex-differential effects in social behavior originate, providing evidence for more targeted intervention strategies in males and females with autism.

Ellen Wilkinson | Rutgers University

Mentor: Vanessa Bal, Ph.D.
Advisors: Richard Hastings, Ph.D. and Andrew Jahoda, Ph.D.

Measuring Depression and Low Mood in Minimally-Verbal Autistic Adults: Establishing and Adapting Tools to Assess Emotional Well-Being

Despite awareness that depression is common in autistic people, the mental health of minimally verbal (MV) autistic adults has received inadequate attention. Part of the problem is the lack of valid tools to assess depression in MV autistic adults. This study will investigate the utility and appropriateness of using surveys administered by a caregiver around depression and will gather information about behaviors that caregivers believe reflect low mood or depression. This project addresses a gap in mental health supports for MV autistic adults and will assist clinicians in determining which tools should be used for people with autism who show signs of depression but cannot verbally communicate their feelings.

Postdoctoral Fellowships

Susan Kuo, Ph.D. | Broad Institute of MIT and Harvard

Mentor: Michael Talkowski, Ph.D.
Advisor: Somer Bishop, Ph.D.

Utilizing Developmental Milestones to Predict the Usefulness of Genetic Testing in People with Autism

Genetic testing is recommended for all children with autism. However, many children receive test results that reveal mutations in genes that have not yet been associated with autism. Unfortunately, these variants of uncertain significance can cause confusion and problems for parents seeking clinical diagnoses and support. This study will utilize machine learning to integrate genetic findings with the child’s attainment of key developmental milestones, because often milestone delays are associated with rare genetic disorders. Eventually, this research could lead to a brief, low-cost clinical prediction tool that increases the diagnostic certainty of genetic testing in autism.

Carissa Sirois, Ph.D. | University of Wisconsin at Madison

Mentor: Xinyu Zhao, Ph.D.
Advisor: Craig Erickson, Ph.D

Developing Therapeutics for Autism and Fragile X Syndrome Based on Divergent Brainwave Patterns

Even in cases of autism with a known genetic mutation, there can be differences in the presentation of symptoms, which is also known as “phenotypic heterogeneity.” One way to measure this variability across individuals with autism is by examining brainwave patterns. Earlier research in people with Fragile X Syndrome has shown that individuals have different patterns of brainwave activity, which may predict their response to treatments. Building on this research, the fellow will collect cells from individuals with Fragile X Syndrome and turn them into neurons. These cells will then be tested for their own electrical activity, validating the brainwave data collected earlier. This study will then take the research a step further by examining if and how different therapeutics affect these neurons in different ways, leading to more targeted therapeutics.

Accelerator Awards

Calliope Holingue, MPH, Ph.D. | Kennedy Krieger Institute

Expediting Our Understanding of Gastrointestinal Issues in Autistic Adults

Up to 90% of people with autism experience GI distress. Although these symptoms often occur in children and adults, there is a lack of research focused on addressing GI dysfunction in autistic adults. A current study is gathering input from a group of autistic adults in order to develop a set of recommendations for improving GI health in adults. This grant will provide funding to expedite data collection, analysis, and dissemination of the outcomes of this study so that results can be seen up to a year earlier.  These recommendations will shape future research by prioritizing the most relevant GI concerns identified by autistic adults and interdisciplinary collaborators, leading to the development of better treatments and overall approaches to GI health in people with autism.

Elizabeth Kaplan-Kahn, Ph.D. | Children’s Hospital of Philadelphia

Advisor: Judith Miller, Ph.D.

Improving QoL Measures for Minimally Verbal Autistic Children with Cognitive Disability

Quality of Life (QoL) outcome measures have traditionally excluded autistic individuals with minimal verbal ability or cognitive disability. The Patient-Reported Outcomes Measurement Information System (PROMIS®) Autism Battery – Lifespan (PAB-L) is a
recently developed instrument to measure autistic QoL across the lifespan. Although PAB-L has been shown to be an acceptable QoL measure in autism, nonverbal people with cognitive disability were underrepresented among participants in the original validation studies. This grant will expand the research on the PAB-L to examine whether it is appropriate in those with profound autism, and also determine what changes, if any, should be made to effectively measure quality of life in this underserved population.

Yael G. Dai,  Ph.D and Daina M. Tagavi, Ph.D. | University of Massachusetts, Boston

Advisors: Alice Carter, Ph.D. and Wendy Stone, Ph.D.

Validating an Online Autism Diagnostic Tool

Early intervention is vital for children on the autism spectrum but is often only available after a formal diagnosis. Because of the COVID- 19 pandemic, many assessments are now conducted online. This change has sometimes occurred without studying whether modifications made to support online assessments affect the outcomes of the assessments. Researchers at the University of Massachusetts Boston, the University of Washington, Rush University Medical Center, and Michigan State University recently adapted an assessment protocol (the Communication Play Protocol; CPP), to be conducted as an online assessment of ASD (RISE-CPP). ASF’s funding will allow researchers to determine if clinicians can diagnose ASD online using the RISE-CPP protocol as accurately as they can using traditional in-person assessments. An online version has the advantages of possibly reaching a more diverse community and improving opportunities for early intervention.

Undergraduate Summer Research Grants

David Barrett | Vanderbilt University 

Mentor: Tiffany Woynaroski, Ph.D., CCC-SLP

Understanding the mechanisms of sensitivity to sound in ASD

Hypersensitivity to auditory stimuli, including even regular sounds and voices, is seen in a high percentage of people with autism. This project will expand on existing research at Vanderbilt looking at brain activity in autistic and non-autistic individuals with different levels of sound tolerance to understand the factors that play a role in the brain’s response to noise.

Jessie Greatorex | Michigan State University

Mentor: Brooke Ingersoll, Ph.D., BCBA-D

Strengthening parent training in community mental health clinics

Many autism referrals in low-resource settings originate from community mental health care clinics. Unfortunately, many mental health care providers are not trained in autism interventions and do not have the appropriate resources to provide support to parents or provide parent training for early developmental interventions. This fellow will work directly with ABA agencies that contract with Medicaid to determine how clinicians can better support parents participating in parent- mediated interventions.

Grace Hajjar | University of California at Los Angeles

Mentor:  Catherine Lord, Ph.D.

Determining the effectiveness of the BOSCC in females and people of color

Given the historically higher prevalence of white males in autism research studies, many autism diagnostic and outcome instruments have not been specifically validated in people of color or in females. This study will recruit women and individuals from racially and ethnically diverse communities to understand how a measure of treatment outcome, called the BOSCC (Brief Observation of Social Communication Change), can be used more effectively in these communities.

Chavely Gonzalez Ramirez | University of North Carolina at Chapel Hill

Mentor:  Ben Philpot, Ph.D.

Understanding the expression of ASD Gene UBE3A in the Rhesus Macaque

The UBE3A gene is thought to be responsible for Dup15q Syndrome, one of the genetically derived autism spectrum disorders (ASD). Despite its clinical importance, we know very little about UBE3A distribution in the human brain. Most researchers assume it closely mirrors that of the rodent brain. This lack of knowledge could be catastrophic if the distribution of UBE3A in the human brain is improperly inferred from rodent studies and leads to inappropriate delivery and treatment strategies for autism. To assure the safe targeting of therapeutic approaches to normalizing UBE3A levels in individuals with Dup15q Syndrome, this fellow will study UBE3A developmental expression in the closest proxy we can get to the human brain – the brain of the rhesus monkey.

Meagan Tsou | Boston Children’s Hospital

Mentor:  Susan Faja, Ph.D.

Examining the impact of early intervention on executive functioning

Executive functioning is the ability to manage daily life, follow directions and handle emotions — and has been reported to be significantly impaired in individuals with ASD. This project will take advantage of an existing longitudinal study to examine the specific role and active ingredients of early intervention from ages 2-4 on executive functioning. The fellow will also examine whether demographic factors, including race and ethnicity, play a role in the effectiveness of the intervention.