PROJECT PI: John-Paul Yu MD PhD, Assistant Professor, in Radiology (Neuroradiology), Psychiatry, and Biomedical Engineering at University of Wisconsin–Madison
PROJECT FOCUS: To identify how altered gut microbiome in IBD leads to increased risk for ASD by developing a novel human pediatric ASD/IBD microbiome model in mice.
PROJECT AIMS: We will identify altered gut-brain-behavior development in our model and directly test the ability of replacing altered microbiota-derived metabolites to rescue brain and behavior impairments relevant to ASD. Our work will provide the first test of human ASD/IBD microbiota to produce ASD-relevant brain and behavior phenotypes through altered metabolite and brain immune cell signaling. Lastly, we will employ state-of-the-art quantitative multi-compartment diffusion weighted imaging to develop a neuroimaging biomarker for both diagnostic accuracy and to track a microbiota-based therapeutic response.

PROJECT PI: Jennifer Frankovich MD MS, Clinical Professor, Dept of Pediatrics, Stanford University/Lucile Packard Children’s Hospital
PROJECT FOCUS: Illuminating biological underpinnings in behavioural regression in ASD compared to healthy controls and Pediatric Acute-onset Neuropsychiatric Syndrome (PANS).
PROJECT AIMS: Using our longitudinal clinical database and biobank, we aim to describe the clinical and immunological course of patients with autism (n=18) followed in our IBH Clinic through different states (flare, improved, chronic) and compare these data to findings in patients with PANS and to hospital/clinic controls. Immune studies will include monocyte profiles, single-cell RNA sequencing, the effects of plasma from autism patients on healthy monocytes, and blood-brain endothelial cells. Since these experiments will use only a fraction of the stored samples, the remaining will be reserved for cytokine/proteomic profiles, ATAC-seq, and functional assays, so that all these data can be correlated with the clinical data for informing biomarker discovery and clinical trials.

PROJECT PI: Karen Parker PhD, Associate Professor (Research) of Psychiatry & Behavioral Sciences, Stanford University
PROJECT FOCUS: Discovery of clinical biomarkers for improved detection and treatment of autism
PROJECT AIMS: To identify robust protein markers of ASD for novel therapeutic target identification and diagnostic test development using an innovative CSF-first strategy. This project is based on promising preliminary data and is statistically well-powered to detect effects. Our specific aims are two-fold: Aim 1: Use the full power of Olink’s state-of-the-art proteomic platform to identify proteins in banked CSF samples that enable accurate differentiation of children with ASD from unrelated child controls. Aim 2: Assess whether the multiplex CSF protein profile is evident in banked blood samples from children with ASD and unrelated child controls

PROJECT PI: Harumi Jyonouchi MD, Board Certified Allergist/Immunologist, Saint Peter’s University Hospital, Rutgers-Robert Wood Johnson Medical School
PROJECT FOCUS: Immune mediated inflammation in long COVID patients with or without ASD
PROJECT AIMS: The long-term goal of our research is to determine the underlying mechanisms of immune
mediated inflammation in long COVID patients with or without ASD. The immediate goals of this proposal are to assess how COVID infection triggered long-term changes in the innate immune system affect ASD subjects in comparison with non-ASD long COVID subjects. Completion of this project will help identify 1) key pathological changes in long COVID symptoms in ASD subjects, and 2) how these changes affect clinical features of ASD and assess treatment options in these subjects.

PROJECT PI: Chandra Menendez PhD, Postdoctoral Fellow in the Department of Microbiology and Immunology at the University of Oklahoma Health Sciences Center
PROJECT FOCUS: The human translational study will identify biomarkers and advance the identification and treatment of basal ganglia comorbidities in ASD
PROJECT AIMS: To investigate the hypothesis that infections and basal ganglia autoimmunity are risk factors in ASD comorbidities. The project will attempt to determine putative AAb biomarkers (including AAbs that activate the dopamine receptors) and immunophenotypic signatures in ASD and correlate them with ASD comorbidities or immune dysregulation. It will also investigate immunophenotypic signatures in ASD subtypes with and without comorbidities.

PROJECT PI: Dr Alessio Fasano, Professor of Pediatrics & Vice Chair of Research at Mass. General Hospital, Professor of Nutrition at Harvard T.H. Chan School of Public Health.
PROJECT FOCUS: gut permeability/microbiome /immune response interplay in autism
PROJECT AIMS: advance our understanding of ASD pathogenesis and the mechanisms behind increased gut permeability; identify biomarkers to stratify the ASD population in specific subgroups; validate the zonulin inhibitor AT1001 (already showing robust safety profiles in phase 3 human trials with the name Larazotide acetate) as a possible personalized therapeutic strategic treatment, so posing foundations for future clinical trials in ASD.

PROJECT PI: Paul Ashwood, PhD, Professor of Microbiology and Immunology, MIND Institute, University of California Davis.
PROJECT FOCUS: understand underlying pathological pathways in gastrointestinal (GI) issues in autism and develop treatment strategies.
PROJECT AIMS: determine the mechanisms of increased innate immune activation. The project will examine the hypothesis is that macrophage dysfunction in autism is due to epigenetic changes that cause increased immune activation, decreased endotoxin/bacterial tolerance, and lead to inflammation. The researchers will aim to identify a panel of biomarkers, or biological signatures, that could be used for patient stratification, development of new therapeutic targets, or to monitor treatment responses.

PROJECT PI: Richard Frye, MD PhD, Pediatric Neurologist, Phoenix Children’s Hospital.
PROJECT FOCUS: mitochondrial dysfunction in regressive autism. About one-third of children with autism spectrum disorder demonstrate a major neurodevelopmental regression – loss of previously acquired language and social interaction skills, as well as emergence of restricted and repetitive behaviors.
PROJECT AIMS: The overall goal of this study is to develop better treatments for children with autism. In order to reach this aim, the investigators will further characterize mitochondrial dysfunction in their in vitro models and test agents that potentially modulate mitochondrial function in order to discover novel targeted treatments for this subset of autism.

PROJECT PI: Harumi Jyonouchi, MD, Board-certified Allergist/Immunologist, Saint Peter’s Hospital, Professor of Pediatrics at Rutgers Robert Wood Johnson Medical School.
PROJECT FOCUS: immune mediated inflammation that affects not only the brain but also other organs has been implicated in many of the observed clinical features in autism. However, inflammation in autism appears not associated with specific environmental factors, but appears to be driven by innate immune memory (IIM) responses that are generated by metabolic and epigenetic changes triggered by an initial stimulus.
PROJECT AIMS: determine the underlying mechanisms of immune mediated inflammation and their effects on the development and progress of autism.

PROJECT PI: Dr. Juergen Hahn, Professor & Department Head, Biomedical Engineering, Rensselaer Polytechnic Institute.
PROJECT FOCUS: analyzing measurements of metabolite concentrations of the folate-dependent one-carbon metabolism and transsulfuration pathways to distinguish children diagnosed with autism from their typically-developing peers.
PROJECT AIMS: replicate the results on a new, large cohort of children using state-of-the-art technologies appropriate for a commercial lab test; develop the foundation for autism biomarkers to be used for diagnosing autism and for assessing efficacy of treatments.

PROJECT PI: Stuart Lipton, MD, PhD, Professor of Molecular Medicine, Scripps Research.
PROJECT FOCUS: partial loss of MEF2C activity is known to lead to ASD, intellectual disability, epilepsy and other neurological symptoms. Since MEF2C is a major regulator of the expression of various other proteins known to be involved in various forms of ASD, such a drug may be an effective treatment for a wide variety of ASDs.
PROJECT AIMS: optimize lead compounds discovered by Lipton’s lab in order to develop drug candidates to treat a specific type of autism by increasing the activity of MEF2C neuronal transcription factor.

PROJECT PI: Harumi Jyonouchi, MD, Board-certified Allergist/Immunologist, Saint Peter’s Hospital. Professor of Pediatrics, Rutgers Robert Wood Johnson Medical School.

PROJECT PI: James Adams, PhD, President’s Professor, Arizona State University.

PROJECT PI: Robert Naviaux, MD, PhD, UC San Diego

PROJECT PI: Edward Quadros, PhD, SUNY Downstate.