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Neurochemistry

In neurology and psychiatry, many chronic disorders feature cyclical recurrence of attacks (e.g. epilepsy, migraine, and cluster headaches) or relapses (e.g. mood disorders, substance use disorders, and multiple sclerosis), resulting in long-duration patterns of fluctuating episodes of disease severity. The neurobiological underpinnings of these disorders are being slowly unraveled, and studies suggest that chemistry oscillations in body fluids play important roles. However, the concentration dynamics over small- (seconds, minutes, hours) and large-time scale horizons (days, weeks, months) are unknown for most of these chemicals, and the causality between the chemistry oscillations and disease episodes also remains unclear. Our goal is to understand the biological relevance of these oscillations and to use this knowledge to develop more effective therapies for cyclical brain disorders. We are working on four main projects:

Glutamine Synthetase and Epilepsy

The enzyme glutamine synthetase is found in all living organisms and catalyzes the conversion of glutamate and ammonia to glutamine. However, the enzyme does not work properly in some people with epilepsy, and studies have suggested that glutamine synthetase malfunction plays an important role in the causation of temporal lobe epilepsy and glioblastoma-associated epilepsy. We are studying this enzyme and expect that novel, glutamine synthetase targeted interventions will someday be available to treat people with serious epilepsy more effectively and with fewer side effects than the current standard of care does.

The Metabolome of Seizures

The hallmark symptoms of epilepsy are recurrent, spontaneous seizures, but despite decades of research, the seizure-triggering mechanisms for most types of epilepsy remain unknown. We recently discovered that several brain chemicals (e.g., γ-aminobutyric acid, isoleucine, leucine, and valine) changed in concentration hours before a spontaneous seizure in humans and animals with epilepsy, suggesting chemistry oscillations play critical role in seizure triggering. We are studying the biological relevance of these and other chemistry oscillations, using state-of-the art mass spectrometry metabolomics and chemical sensors.

Chemical Biomarkers of Tobacco Exposure and Addiction

The Yale Tobacco Center of Regulatory Science conducts a series of studies to understand the role of flavors, sweeteners, and other constituents of tobacco products in modulating appeal and addiction to nicotine and tobacco. We support these studies by measuring nicotine, nicotine metabolites, minor tobacco alkaloids, flavorants, cannabinoids, and tobacco-derived carcinogens in biological samples from the study participants.

Biochemical Mechanisms of Relapse in Psychiatric Disorders

Relapse is a feature of many psychiatric disorders, but the molecular mechanisms of relapse are incompletely understood. We are investigating the metabolome of people with psychiatric disorders to identify chemical mechanisms and biomarkers of relapse.

Analytical Chemistry and Metabolomics Services

We provide high-quality, analytical chemistry and metabolomics services on a collaborative or fee-for-service basis through the University Service Provider (USP) mechanism at Yale University. The analytical performance of all assays has been validated with respect to accuracy, precision/reproducibility, limit of detection, and linearity. The within-day and between-day quality of the assays are documented and tracked by an experienced technician and overseen by a board-certified clinical pathologist. For enquiries about the service, such as pricing, turnaround time, and sample types, please email Tore Eid, MD, PhD.

Our assays are for research only, not for diagnostic or clinical use. For CLIA’88 approved clinical laboratory assays, please use the Clinical Laboratory Service at Yale New Haven Hospital.