Dr. Judith Ross is a physician scientist in the Department of Pediatrics and is board certified in Pediatrics and Pediatric Endocrinology. Her lab has focused on neurodevelopmental outcomes in children with X and Y chromosome disorders (XYY syndrome, Klinefelter syndrome, Turner syndrome), with over 25 years of NIH-funded pediatric clinical research. 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 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, 1/1000 males), and their increased autism risk suggests the involvement of sex-linked genes in autism (Y chromosome genes related to brain development and function, thereby increasing ASD risk). Current clinical research in Dr. Ross’ lab takes advantage of the detailed ASD characterization of clinical ASD populations, 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 analysis. This translational research will result in new bidirectional insights (“bench to bedside”) and will advance our understanding of sex differences, ASD neurobiological mechanisms, relevant biomarkers, and future disease-specific treatments.
- 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 and may be related to the male predominance of ASD.
- The Y chromosome gene, neuroligin 4Y (NLGN4Y), encodes a synaptic cell adhesion molecule. NLGN4Y expression is increased in XYY, which may provide 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. Roberts, CHOP) and may provide biomarkers for ASD behavioral features.
The eXtraordinarY Babies Study: |Natural History of Health & Neuro-development in Infants and Young Children with Sex Chromosome Trisomy.
NIH/NICHD 1R01HD091251-01 (PI: Tartaglia, co-I: Ross) 9/06/2017–06/30/2022. The aims are to describe the natural history of young children with sex chromosome trisomy from infancy to 5 years, with a focus on early predictors of neurodevelopmental and cardiometabolic outcomes.
Mean Diffusivity (MD)
Legend - Figure 1. Elevated Mean diffusivity (MD) of the left arcuate fasciculus (AF) in XYY+ASD cohort (TJU left), analogous to those observed in idiopathic ASD (CHOP, right) [Click for larger image]
Neural Correlates of the Y Chromosome in Autism: |XYY Syndrome as a Genetic Model
Department of Defense Idea Research Grant Proposal # AR140197 (MPI: T.Roberts, J. Ross, 7/1/15-6/30/18): This study evaluates similarities in autism features of boys with XYY syndrome versus idiopathic autism.
Neuroimaging in ASD Populations
R21 MH109158-01A1 (MPI: T. Roberts, J. Ross, 04/01/16-3/31/18) "Structural and Functional Characteristics of XYY - Relationship to ASD." This study evaluates potential neuroimaging biomarkers for autism in populations with autism spectrum disorder.
Increased WM and GM in boys with XYY
Legend - Figure 2. Increased WM and GM in boys with XYY versus typically developing boys (frontal, parietal-occipital, temporal cortices)
The IDeA States Pediatric Clinical Trials Network
NIH/NICHD 1UG1HD090915-01 (PI: J.Ross) Delaware Nemours/duPont Hospital for Children Site for the IDeA States Pediatric Clinical Trials Network, 9/21/16-8/31/20. The IDeA States Pediatric Clinical Trials Network functions as one component of the overall Environmental influences on Child Health Outcomes (ECHO) Program.
Center for Pediatric Research
NIH/NIGMS 1P30GM114736-01 (PI: T Shaffer, co-I: J Ross)
(CPR) 08/01/2015 – 07/31/2020. Project goals for this Center of Biologic Research Excellence (COBRE) study include development of pediatric translational research programs.