The National Institute of Child Health and Human Development (NICHD) awarded a 5-year, $504,283 Project Grant (CFDA 93.865 - Child Health and Human Development Extramural Research) to the Icahn School of Medicine at Mount Sinai. The grant will fund a study examining the epidemiology and risk factors for autism spectrum disorder (ASD) in children born preterm, and determine if the genetic architecture of ASD differs between preterm and term-born children. The study will create a prospective...
This Project Grant award from the National Institute of Mental Health (NIMH), under the Mental Health Research Grants program (CFDA 93.242), provides $251,250 to The Feinstein Institutes for Medical Research to study sex-dependent dysregulation of parvalbumin interneurons as a pathway to autism spectrum disorder (ASD). The key objectives are to: 1) Determine if the reduction in parvalbumin-expressing interneurons observed in male mice exposed in utero to anti-CASPR2 antibodies is associated with...
This federal Project Grant award of $746,183 from the National Institute of Mental Health (NIMH) under CFDA Program 93.242, Mental Health Research Grants, supports a prospective, longitudinal study on the association between autonomic nervous system (ANS) dysfunction in preterm infants and the development of autism spectrum disorder (ASD) and other neurodevelopmental impairments (NDIs). The key objectives are to: 1) evaluate preterm ANS dysfunction as an ASD-specific etiological mechanism in...
This Project Grant award from the National Institute of Child Health and Human Development (NICHD), under the Child Health and Human Development Extramural Research program (CFDA 93.865), provides $253,500.00 to the Icahn School of Medicine at Mount Sinai to conduct research on resolving the relationship between mitochondrial dysfunction and the impact of non-syndromic autism spectrum disorder-related risk genes on neuronal structure and function. The research aims to establish human induced...
This Project Grant awarded by the National Institute of Child Health and Human Development (NICHD), under the Child Health and Human Development Extramural Research program (CFDA 93.865), will support research to investigate how the gut microbiome composition impacts gastrointestinal (GI) and central nervous system (CNS) function in a mouse model of autism spectrum disorder (ASD). The $430,375 award to the partnership between Henry Ford Health and Michigan State University Health Sciences will...
This Project Grant award of $324,464 from the National Institute of Allergy and Infectious Diseases (CFDA 93.855 - Allergy and Infectious Diseases Research) aims to characterize the early childhood neurodevelopmental impacts of infants exposed to maternal SARS-CoV-2 infection during pregnancy. The grantee, Ann & Robert H Lurie Children's Hospital of Chicago, will utilize their longitudinal SNIPP cohort of approximately 4,000 mother-infant pairs affected by SARS-CoV-2 infection during...
The National Institute of Child Health and Human Development (NICHD) awarded a $431,750 Project Grant (CFDA 93.865 - Child Health and Human Development Extramural Research) to Rutgers, The State University of New Jersey, to investigate how the cytokine interleukin-6 (IL-6) affects the proliferation, specification and gene expression of human and mouse secondary neural progenitor cells. The goal is to establish IL-6 as a key target for intervention to prevent neurodevelopmental disorders like...
This Project Grant award from the National Institute of Mental Health (NIMH), under the Mental Health Research Grants program (CFDA 93.242), provides $165,796 to the University of California, Los Angeles (UCLA) to conduct research on the impact of autism spectrum disorder (ASD) genetic risk on microglial function and neuronal-microglial interactions. The research aims to leverage human stem cell culture and 3D human cortical spheroid models to assess how ASD genetic risk factors, such as...
This Project Grant award from the National Institutes of Health (NIH) Office of the Director, under the Trans-NIH Research Support program (CFDA 93.310), will provide $164,561 to the University of California, Davis (UC Davis) to study the relationship between prenatal exposure to endocrine disrupting chemicals, child neurodevelopmental disorders, and the potential mediating role of cytokines and DNA methylation. The research aims to: (1) examine associations between prenatal endocrine disrupting...
This $664,837 Project Grant awarded by the National Institute of Allergy and Infectious Diseases (NIAID) under the Allergy and Infectious Diseases Research program (CFDA 93.855) aims to comprehensively screen newborns for in-utero SARS-CoV-2 infection and assess associated immune responses and clinical outcomes. The primary objectives are to: 1) Identify newborns with in-utero SARS-CoV-2 infection using a multi-faceted approach involving antibody and PCR testing of cord blood, placental...
CONTRIBUTION OF MATERNAL IMMUNE ACTIVATION, VIRAL INFECTION AND EPIGENETICS TO AUTISM--A COMMUNITY-BASED CASE CONTROL STUDY - PROJECT SUMMARY/ABSTRACT AUTISM SPECTRUM DISORDER (ASD) IS A BROAD RANGE OF RELATED NEURODEVELOPMENTAL DISORDERS THAT ARE EXPRESSED WITHIN THE FIRST 2 TO 3 YEARS OF LIFE AS STEREOTYPIC BEHAVIORS, AND LANGUAGE AND SOCIAL-EMOTIONAL IMPAIRMENTS. ASD AFFECTS ABOUT 1 IN 59 CHILDREN IN THE UNITED STATES AND CARRIES A HIGH ECONOMIC COST TO FAMILIES AND COMMUNITIES. WHILE THERE IS A CONTRIBUTION OF HEREDITY, A GROWING BODY OF RESEARCH SUGGESTS THAT ASD HAS ORIGINS IN UTERO. SPECIFICALLY, EVIDENCE IS ACCUMULATING THAT PRENATAL INFLAMMATION IS A CRITICAL EXPOSURE IN THE CAUSAL PATHWAY OF AT LEAST A SUBSET OF ASD. NOTABLY, THIS EXPOSURE MAY OPERATE THROUGH SEX-DIMORPHIC EFFECTS ON THE PLACENTA ON FETAL BRAIN DEVELOPMENT, CONSISTENT WITH THE HIGH ASD RISK FOR MALES RELATIVE TO FEMALES. IN OUR COMMUNITY-BASED HOSPITAL POPULATION, UNIQUE DUE TO MANDATED UNIVERSAL PLACENTAL HISTOPATHOLOGY ASSESSMENT AND LINKAGE TO PEDIATRIC COMMUNITY CARE, PILOT ANALYSES IDENTIFIED A 3-TO-7-FOLD INCREASED RISK OF CHILDHOOD ASD ASSOCIATED WITH PRENATAL EXPOSURE TO ACUTE AND/OR CHRONIC INFLAMMATION (AI, CI). THIS MARKER WAS SEEN IN ~25% OF LOW-RISK CHILDREN EVENTUALLY DIAGNOSED WITH ASD. THESE INFLAMMATORY PLACENTAL PATHOLOGIES WERE NOT MARKED BY ANY MATERNAL SIGNS OR SYMPTOMS DURING PREGNANCY. IN ADDITION, WE IDENTIFIED A 13-FOLD INCREASED ODDS OF ASD RISK WITH PLACENTAL VILLOUS MALDEVELOPMENT (PVM). WE PROPOSE HERE TO TEST PATHWAYS FROM THESE PLACENTAL HISTOPATHOLOGY DIAGNOSES TO EVENTUAL ASD DIAGNOSIS. WE WILL BEGIN WITH TARGETED FORMALIN-FIXED PARAFFIN-EMBEDDED (FFPE) PLACENTAL HISTOPATHOLOGY OF AI, CI, AND PVM. WE WILL THEN EMPLOY DETAILED AND QUANTITATIVE IMMUNOPHENOTYPING OF PLACENTAL-DECIDUAL TISSUE AT THE PLACENTAL-MATERNAL INTERFACE. WE CAN THOROUGHLY PROFILE CELL TYPE, CELL FUNCTION MARKERS, AND INFLAMMATION ACTIVATION/APOPTOSIS TARGETS AT THE SAME TIME BY USING COMPUTER-ASSISTED DEEP LEARNING THAT ALLOWS PRECISE TRACKING OF IMMUNOLABELING AND MINIMIZES CONCERNS OF LABEL OVERLAP THAT CAN CONFOUND INTERPRETATION OF IMMUNOFLUORESCENT PREPARATIONS. WE WILL NEXT ASSESS NEWBORN CIRCULATING LEVELS OF CYTOKINES, CHEMOKINES, AND GROWTH FACTORS, ALTERATIONS OF WHICH ARE KNOWN TO IMPACT NEURODEVELOPMENTAL PROCESSES KEY TO THE GENESIS OF NEURONAL DYSFUNCTION MANIFESTED IN ASD. WE WILL ALSO EXAMINE EPIGENETIC PATHWAYS BY ASSESSING DNA METHYLATION IN THE PLACENTA AND ITS LINK TO INFLAMMATION AND PVM. OUR ANALYSES WILL TEST THESE AS PATHWAYS FROM PLACENTAL/DECIDUAL TISSUE MARKERS OF INFLAMMATION AND/OR PVM TO ASD DIAGNOSIS. NO OTHER ASD CASE-CONTROL SAMPLE IN A COMMUNITY-BASED POPULATION HAS UNIVERSAL ACCESS TO FFPE TISSUE. THIS PROPOSED PROJECT WILL OPEN A UNIQUE WINDOW ON THE PRENATAL ENVIRONMENT UNDERLYING ASD. CLARIFICATION OF THE PATHWAYS OPERATING IN COMMUNITY-BASED ASD WILL ELUCIDATE THE MECHANISMS INVOLVED IN ASD RISK.