Research Focus
A Multi-Dimensional Approach
We want to identify treatable, biologically valid mechanism and causes of disease that enable us to develop and validate practical and safe treatments. We fund projects at our research laboratory and clinical sites, and invest in promising projects championed by other researchers and educators. Some examples of topics that we research include:
Mitochondrial Dysfunction
Abnormalities in mitochondrial function appear to affect a significant number of children with autism. Our recent research suggests the nature of mitochondrial dysfunction in ASD is distinct in its metabolic nature and with respect to molecular signaling pathways. We have developed a model of mitochondrial dysfunction related to ASD based on cell lines to allow us to study mitochondrial function in the laboratory in detail.
See ResearchBiomarkers
Some children with ASD demonstrated abnormal markers of metabolism. The identification of metabolic abnormalities in ASD provides important clues as to possible causes and treatments. Metabolites in critical pathways may help us identify reliable biomarkers for the diagnosis and treatment of autism. The methylation pathway is particularly important because it is intimately involved in epigenetics.
See ResearchThe Microbiome
Increasing evidence suggests that the enteric microbiome plays a critical role in the etiology and symptomatology of some cases of ASD. To better understand this connection, we are focusing on approaches to study and manipulate the enteric microbiome to improve autism symptoms. We have also investigated the clinical and basic research aspects of enteric microbiome metabolites on mitochondrial function
See ResearchCerebral Folate Deficiency
Cerebral Folate Deficiency (CFD) happens when folate, 5-MTHF, is normal in the blood but unusually low in the cerebrospinal fluid (and brain). This is sometimes caused by genetic mutations, mitochondrial disorders, and/or autoantibodies to the FRα transporter. We have found a link between CFD and some cases of ASD, and we are investigating promising treatments.
See ResearchPrenatal Exposures
Several manmade chemicals have not been tested for their effects on developing brains. Researchers have found toxic chemicals in the umbilical cord blood of babies. More research is needed to understand how these chemicals may be toxic to the developing nervous systems of children. Understanding this can improve the probability of a safe, full-term pregnancies.
See ResearchEpigenetics
Epigenetics is a process that dynamically turns genes on and off. We are learning that epigenetics is extremely important, as normal development can be easily derailed if the wrong genes are activated or inactivated at critical periods. In fact, the different stages of development are thought to be controlled by coordinated activation and inactivation of large numbers of genes.
See ResearchEnvironmental Influences
Genetic abnormalities in autism spectrum disorders (ASD) are widely-accepted; however, recent studies point to an equal contribution by environmental factors, particularly environmental toxicants. New publications investigating potential associations between environmental toxicants and ASD examine the estimated toxicant exposures in the environment during the preconceptional, gestational and early childhood periods; look for biomarkers of toxicants; and examine potential genetic susceptibilities to toxicant exposure.
See ResearchImmune Dysfunction
Recent studies suggest that ASD is associated with immune system dysfunction. In individuals with ASD, inflammatory cytokines are often elevated in the blood and brain. Children with ASD sometimes have autoantibodies to brain tissue as well as to non-brain tissue such as the folate receptor alpha (FRα) and mitochondria. Another recent area of interest is in the overlap between ASD and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infection (PANDAS) and Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS).
See ResearchTreatments
Treatments targeting some of the abnormalities seen in ASD including neurotransmitter abnormalities, imbalances in glutamate and acetylcholine, sleep onset disorder (with behavioral therapy and melatonin), and metabolic abnormalities in folate, cobalamin, tetrahydrobiopterin, carnitine, and redox pathways are being investigated. Treatments of epilepsy and seizures, mitochondrial and immune disorders, gastrointestinal abnormalities, and imbalances in the enteric microbiome may one day become the standard of care for ASD.
See Research