Philadelphia University + Thomas Jefferson University

Jefferson Autism Research Program

Autism is one of the most prevalent neurodevelopmental disorders of childhood affecting 1 in 66 children. Individuals with Autism Spectrum Disorders show delays and difficulties in social communication abilities and restrictive and repetitive patterns of behaviors including atypical responses to sensation, which impact their ability to fully participate in daily life. Autism is a complex brain disorder that has no single known cause or cure.

Autism Researchers - Schaaf, Ross, Merry, Dalva

Jefferson researchers are working together to help those living with autism lead productive and meaningful lives.  At Jefferson, we are conducting research on the neurobiological basis of autism that will help develop targeted interventions to address both the causes and symptoms of autism. We are translating research into interventions to improve function and quality of life. The unique Jefferson Autism Programmatic Research Program spans molecular, genetic, synaptic, and functional aspects of the disease and translates these findings into solutions that help children and families with autism participate fully in their everyday activities. Central to this research mission is the integrated training of students to be the next generation of autism researchers and clinicians. Drs. Schaaf, Dalva, Merry and Ross are leading programs of research in clinical interventions, synapse and molecular biology, and genetic models of autism to advance the understanding and treatment of autism. Together, the Jefferson team is advancing autism research by discovering the causes and treatment for autism.

Save the Date
EAGLES AUTISM CHALLENGE

Jefferson’s Autism Programmatic Research Team will is one of the beneficiary partners of the inaugural Eagles Autism Challenge on May 19, 2018.

For more information on how to get involved, please visit Jefferson.edu/EaglesAutismChallenge.

Laboratory of Roseann C. Schaaf, PhD, OTR/L, FAOTA

Autism

Dr. Schaaf’s program of research in autism is seeking to understand a key feature of autism – sensory differences.   Nearly nine in 10 children and adults with autism have difficulty with sensory perception and integration. They may be hypersensitive to sounds, sights, and the feel of fabric or other sensations.  They may have difficulty perceiving and/or integrating auditory and visual information needed for language, or touch and movement sensations needed for balance.  These issues can be debilitating, affecting learning, socializing, and even basic needs like eating. Jefferson’s Autism Lab studies how the brain perceives and integrates sensory information, how differences in sensory processing and integration impacts life skills, and whether occupational therapy interventions designed to treat these sensory issues result in long-lasting changes in functional skills needed for success in everyday life.

With funding from the National Institute of Child Health and Human Development, Dr. Schaaf’s lab is conducting a large clinical trial of occupational therapy for children with autism.  In collaboration with the Albert Einstein Medical Center in the Bronx, NY, this study is investigating how the intervention impacts functional skills needed for daily living and is using a brain biomarker to determine if these changes are reflected in brain’s multisensory integration functions.  Using EEG technology and a unique multisensory integration paradigm, this study is measuring multisensory integration.

Autism Research

In collaboration with Jefferson researchers Drs. Feroze Mohammed, Laura Krisa, Andrew Newberg and Christopher Conklin,; and Jefferson clinicians Cecilia Roan and Rachel Dumont, Dr. Schaaf is extending her NIH study to test whether this intervention also impacts brain connectivity.  Using state-of-the-art imaging technology of fMRI and DTI (Diffuse Tensor Imaging), this research team will provide valuable insight into the plasticity of brain function in children with autism.

Brain Scan

In order to effectively understand sensory functions in autism it is necessary to have sensitive, validate assessment measures.   In collaboration with Adjunct Associate Professor Dr. Zoe Mailloux, an expert in test development, we are developing, field testing and validating a new clinical assessment that can be used to evaluate sensory functions.  This project utilizes an international cohort of occupational therapy clinicians and researchers to collect normative data and perform validity and reliability studies of the tests.

Potvin Research

At the East Falls Campus, Dr. Marie Christine Potvin, PhD., OTR/L is testing the outcomes of a program that provides support for young adults with high functioning autism spectrum disorders who are attending college at the East Falls Campus.  This Coaching in Context for College Success project uses occupational therapy expertise to support and manage learning challenges while simultaneously fostering participation in recreational activities using a coaching in context methodology. Dr. Potvin is also “Expanding Recreational Engagement in Kids with Autism Spectrum Disorder” (EuREKA Project).  The EuREKA Project investigates the effect of an interprofessional approach that combines parent coaching and context therapy (coaching in context) to increase the recreational participation of children with ASD.

The Sensory Aware and Friendly Environments Project (SAFE), led by Dr. Mailloux, is designed to help businesses and organizations in making their facilities and services more sensory aware and friendly.

Dr. Schaaf is also training a cohort of occupational therapy students and clinicians with the skills and knowledge needed to provide needed clinical services to the autism community.  The Autism Advanced Practice Certificate trains therapist to understand and provide evidence-based interventions to individuals with autism to enhance their quality of life and well-being.

Student with Dr. Schaaf

For more information on Dr. Schaaf’s research, please visit the following:

 


Laboratory of Diane E. Merry, PhD

Merry Lab

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder affecting 1 in 68 births and 1 in 42 male births. The molecular mechanisms underlying the increased prevalence of ASD in boys has been elusive.  The male sex chromosome disorder, 47,XYY syndrome (XYY), is associated with an even further increased risk for autism spectrum disorder (ASD), and may reflect an exacerbation of the mechanisms leading to the increased preponderance of ASD in boys. There is strong evidence that ASD represents a heterogeneous disease with underlying dysfunction of synapses.  Moreover, a family of proteins that plays a critical role in synapse formation and stabilization is the Neuroligin family. Two members of this family, Neuroligin 4X and Neuroligin 4Y, are highly homologous proteins for which the encoding genes are located on the X and Y chromosomes, respectively. Dr. Merry’s laboratory is carrying out basic molecular genetic and biochemical studies to understand the basic biology of these highly homologous and, for Neuroligin 4Y, understudied proteins. These studies should shed light on both the basic biochemistry of these proteins and on their functionality when co-expressed in different stoichiometric amounts. In addition, Dr. Merry’s studies to create models that reproduce the increased expression of Neuroligin 4Y observed in boys with 47,XYY should provide important reagents for studying the basic neurobiology of ASD.

Areas of study:

  • Understanding the molecular and biochemical characteristics of the neuroligin proteins produced by the sex chromosome-linked genes NLGN4X and NLGN4Y.
  • Characterizing the glycosylation and trafficking patterns of NLGN4X and NLGN4Y in neurons.
  • Evaluating the physiological effects of enhanced ER localization of NLGN4Y on neuronal physiology, with a focus on ER stress.
  • Defining the NLGN4X and NLGN4Y splice isoform expression patterns in brain.
  • Creating iPS cell lines from boys with sex chromosome aneuploidies and autism spectrum disorders.
  • Creating a mouse model for autism spectrum disorders associated with 47,XYY.

For more information on Dr. Merry’s research, please visit:

 


Laboratory of Matthew Dalva, PhD

The structure of the nervous system varies tremendously across phylogeny; organisms such as the worm, C. elegans, function with a few hundred neurons, whereas humans have tens of billions. Yet communication in all neural circuits is controlled by a remarkably similar, highly specialized site of cell-cell contact known as a synapse. The long-range goal of my research is to discover how synapses are formed and lost, and what impact normal morphology and numbers of synapses have on brain function. Determining how synapses develop and mature will provide profound insights toward the understanding of neuronal networks and brain function. During the last fifteen years, we have made fundamental contributions to our understanding of synapse formation and maturation. Because defects in synaptic structure and function are often associated with developmental disorders and diseases such as autism, addiction, neuropathic pain, epilepsy, and Alzheimer’s, our research will have broad impact on human health.

  1. Mounting evidence indicates that ASD and autism are diseases that impact the function of one of the most elemental structures in the brain – the synapse. Perhaps ASD and other neurological disorders are really synaptopathies – diseases of the synapse.
  2. The Dalva laboratory is a leader in understanding the mechanisms that regulate and control the formation, proper development, and function of synaptic connections.
  3. The Dalva laboratory’s approach is to focus on providing a detailed understanding of the cellular and molecular mechanisms that control the initiation, formation, and maintenance of synaptic contacts.
  4. The Dalva laboratory uses cutting edge imaging, physiology, and makes new molecular tools to see into the synapse and determine its function.
  5. The Dalva lab fundamental research activities are leading them into new areas – including understanding how gender specific differences in proteins might begin to explain why ASD impacts more boys than girls and as well as identifying novel mechanisms that regulate pain.

At Jefferson more broadly: At the newly formed Jefferson Synaptic Biology Center researchers are working to unlock the building blocks that control how neurons talk to one another. The nine laboratories that constitute the center are working on the fundamental mechanisms regulate how neurons form synaptic connections, how the function of these connections are regulated, how circuits that regulate sleep develop, and on the mechanisms that regulate neuronal and brain excitability. Importantly evidence indicated defects in each of these are associated with ASD. Therefore, these efforts will likely help to identify novel therapeutic approaches.

For more information on Dr. Dalva’s research, please visit:

 

Looking into the synapse

Figure 1. Looking into the synapse: The Dalva laboratory uses cutting edge microscopy to look for the first time at how synapses are organized. Here a synaptic spine structure is shown in gray on the left. On the right are proteins that make a synapse – in purple

Looking into the synapse: The Dalva laboratory uses cutting edge microscopy to look for the first time at how synapses are organized. Here a synaptic spine structure is shown in gray on the left. On the right are proteins that make a synapse – in purple and cyan. The clustered organization of these structures is important for the proper function of the synapse.


Organization of Synapse in the Brain

The organization of a synapse in the human brain. The Jefferson Synaptic Biology Center seeks to understand how this structure is formed and functions – to help us understand what goes wrong in the 100 trillion synapses in our brains in diseases like ASD.


Laboratory of Judith L Ross, MD

Judith Ross, MD, is Professor in the Department of Pediatrics at Thomas Jefferson University, Faculty, Farber Institute for Neurosciences at Thomas Jefferson University, and Director of the Extraordinary Kids Clinic (for children with X and Y chromosome variations). She is board certified in Pediatrics and Pediatric Endocrinology and was voted Best Docs for Kids, Philadelphia Magazine and Main Line Magazine (2012-2017). She has over 25 years of NIH-funded pediatric research experience, focused on neurodevelopmental outcomes in children with X and Y chromosome disorders (XYY syndrome, Klinefelter syndrome, Turner syndrome). Results of this research has elucidated neurophysiological, pathological, and molecular genotype-phenotype relationships, and the role of selected X and Y genes in children in health and disease. The current focus of research in her lab involves defining genetic etiologies of autism spectrum disorders (ASD) and establishing clinical-pathophysiological mechanisms in ASD. A known, genetic risk factor for ASD is the male sex chromosome disorder, 47,XYY syndrome (XYY), and their increased autism risk suggests the involvement of sex-linked genes in autism (i.e. Y chromosome genes related to brain development and function, thereby increasing ASD risk). Current NIH funded clinical research in Dr. Ross’ lab takes advantage of the methodical ASD characterization of clinical ASD populations (with Schaaf lab), extensive genetic analyses of a Y chromosome synaptic protein NLGN4Y (with Merry and Dalva labs), innovative neuroimaging expertise (CHOP collaboration), multi-modal data collection, and sophisticated multivariate analysis.

  • Y chromosome effects on brain and behavior. Understanding the differentiation of human brain and behavior is relevant to understanding disorders that differ in males versus females.
  • XYY syndrome is an informative genetic model of Y chromosome gene determinants in male predominant disorders such as ASD.
  • The Y chromosome gene, neuroligin 4Y (NLGN4Y), encodes a synaptic cell adhesion molecule. NLGN4Y expression is increased in XYY, which may provide a biomarker for ASD behavioral features.
  • Neuroimaging approaches suggest that brain regions critical to social cognition are anatomically and functionally altered in boys with XYY, similar to findings in idiopathic autism (Dr. Tim Roberts, CHOP) and may provide biomarkers for ASD behavioral features.
  • Collaborators. The close collaboration between bench and bedside scientists at Jefferson uses an approach that integrates clinical and basic science tools to understand ASD.
    • Judith Ross (TJU): Biomarkers and risk factors for autism spectrum disorder (ASD) in boys with XYY. Overexpression of Y candidate genes in mRNA of boys with XYY.
    • Roseann Schaaf (TJU): Sensory features may be a distinguishing marker of ASD, with similar findings in boys with XYY versus idiopathic ASD.
    • Diane Merry (TJU): Cellular models of Y chromosome candidate genes for ASD, rodent models
    • Matthew Dalva (TJU): Biology of the synapse (defects in the structure and function) related to mechanisms of ASD
    • Tim Roberts (CHOP): Early childhood imaging biomarkers for autism in boys with XYY.
Ross Lab Brain Scans

Figure 1. Increased WM and GM in boys with XYY versus typically developing boys (frontal, parietal-occipital, temporal cortices)


Elevate Mean Diffusivity (MD)

Figure 2. Elevated Mean diffusivity (MD) of the left arcuate fasciculus (AF) in XYY+ASD cohort (TJU right), analogous to those observed in idiopathic ASD (CHOP, left) [Click for larger image}

For more information on Dr. Ross’s research, please visit: