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Irma Rukhadze, PhD
Irma Rukhadze, PhD
VA GLAHS-West Los Angeles Healthcare Center
Dr. Rukhadze’s current work focuses on deciphering and characterizing neural circuitry underlying sleep and breathing disorders. Affected patients experience chronic intermittent hypoxia, with accompanying injury to brain structures, and major cardiovascular, metabolic, digestive and neurocognitive consequences. Her major emphasis is to identify the central, key neural network promoting the sleep-related suppression of upper airway muscles and the processes underlying arousal which break the upper airway obstruction during sleep leading to sleep fragmentation and deprivation.
Dr. Rukhadze’s research is using neuroanatomical, neurophysiological and molecular-genetic approaches. She has identified critical brainstem neuronal populations (noradrenaline, achetilcholine) that provide the excitatory drive to upper airway muscles that help to maintain upper airway patency during wakefulness. She studied the behavior of these neurons and revealed that their activity is suppressed during sleep leading to upper airway collapse and cessation of breathing. Using the chemogenetic technique in conditional knockout mice and Cre-dependent axonal tracing in transgenic mice she has revealed the functional role of pontine glutamatergic neurons in respiratory arousal and defined axonal projections of inhibitory GABAergic neurons of the pontine respiratory group to the downstream medullary targets. She has developed techniques to record the activity of upper airway muscles in chronically instrumented behaving mice. This pioneering work to create the mouse model for studying the control of upper airway muscles across the natural sleep-wake cycle in behaving mice was a major breakthrough in the field of sleep and respiratory neurobiology. She is currently using the combination of transgenic mice and pharmacogenetic technique of designer receptors exclusively activated by designer drugs to target selected neuronal population in a cell-type-specific fashion, and study the in-vivo effects of activation/inhibition of the targeted neurons on activity of upper airway muscles and respiratory parameters during sleep-wake states in freely behaving transgenic mice. She has discovered the function of medullary catecholaminergic neurons in sleep-related suppression of upper airway muscle activity. Dr. Rukhadze is interested to establish the research program of sleep disorders, metabolic dysregulation and digestive diseases.
The overarching goal of these studies is to identify neurons, neurotransmitter receptors and effector systems that can be targeted by pharmacological or genetic treatments to promote undisturbed sleep and breathing and reduce the negative health impact of sleep disorders in growing number of affected patients in the United States and worldwide.