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Kitamoto Laboratory

Research Focus

The primary goal of my current research is to identify critical modifiers of neurological disorders and reveal how they impact penetrance and expressivity of disease phenotypes. Recent advancement in human genomic research has led to the identification of an increasing number of mutations and polymorphisms potentially causative for neurological disorders, such as epilepsy, pain syndromes, Alzheimer's disease, and Parkinson's disease. However, pathogenic gene variants often result in diverse disease conditions, ranging from extremely severe to only minor or even subclinical symptoms. Such phenotypic variations are attributable to intrinsic plasticity of the nervous system and dependent on multiple genetic and environmental factors that can modify neural development and function. The fruit fly Drosophila melanogaster is a well suited model system to gain fundamental insights into the molecular and cellular mechanisms underlying various forms of gene-gene and gene-environment interactions. We are currently focusing on genetic and environmental modifiers of neurological phenotypes (including seizure-like behavior) displayed by mutants of paralytic (para), the sole voltage-gated sodium channel gene in Drosophila. Intriguingly, the results of a recent forward genetic screen for para modifiers and a serendipitous discovery of strong phenotypic suppression by dietary supplementation both indicate the involvement of the innate immune system and lipid signaling in controlling the severity of physiological and behavioral defects in para mutants. Given that the basic biological processes are well conserved between flies and mammals, our findings in the fruit fly have a broad impact on our basic understanding of developmental and functional plasticity of the nervous system and provide valuable clues for novel strategies to prevent and treat neurological disorders resistant to current therapies.

Current Funding

Roles of hemocytes and bioactive lipids in the modulation of neuronal excitability and seizure behavior in Drosophila voltage-gated sodium channel mutants

NIH/NINDS R21NS127364 (02/2022-01/2024), Principal Investigator

Effects of dietary alpha-linolenic acid on SUDEP, seizures, and neural structure and function in mouse models of epilepsy

NIH/NINDS R21NS125130 (06/2022-05/2024), Co-Principal Investigator

Prevention of SUDEP by milk whey: Role of CO2 chemoreception and serotonin

NIH/NINDS R01NS113764 (07/2021-02/2026), Collaborator