Neurobiology of the Bronchopulmonary System
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Principal Investigator: Bradley Joel Undem Organization: JOHNS HOPKINS UNIVERSITY Fiscal Year: 2024 Award: $919,316 Funding agency: National Heart Lung and Blood Institute Project Summary/ Abstract Basic and clinical research over the past decade is shedding new light on the major role played by the nervous system in respiratory pathophysiology, in particular in the “hypertussivity” associated with chronic unproductive cough, in the “airways hyperresponsiveness”” associated with of asthma, and in the airway narrowing and secretions associated with COPD. The evidence supports the hypothesis that these hyperactive disorders are in part secondary to dysregulation of vagal afferent C-fibers that comprise some 75% of the nerves within the respiratory tract. This grant aims to advance our understanding of the nature of the inflammatory mediators (autacoids and cytokines) responsible for activating airway C-fibers and the specific ionic mechanisms underlying this activity. This R35 will replace my two active R01 grants: R01 HL137807 “Mechanisms of Inflammatory Activation of Vagal C-Fibers in the Respiratory Tract” and R01HL122228 “Control of Airway Sensory Nerve Function by Voltage- Gated Sodium Channel Subtypes.” The R35 funding will allow us to go beyond the aims of the R01 grants that focus on healthy animals, and delve into the mechanisms that lead to the neuroplasticity associated with airway inflammation. In particular, we propose to evaluate the neuroplasticity in the afferent nervous system that accompanies viral infection during early life “critical periods” with the hypothesis that such infections cause persistent neuroplastic changes. These changes lead to a hyperreactive neurophysiological state that can last into adulthood. This grant will also allow us to continue to advance more user-friendly technologies for studying airway nerves by taking advantage of modern imaging methodologies. These methods will not only serve to advance our own studies, they will also likely be exported to other laboratories interested in visceral neuroscience in general, and airway neuroscience in particular. We will also continue to advance our techniques and studies into the study of human bronchial innervation. Finally, the award will help keep the path paved for continued mentoring of young investigators interested in pursuing airway neuroscience research. Terms: <21+ years old><Adult><Adult Human><Airway Disease><Airway Hyper-responsiveness><Animals><Asthma><Autacoids><Award><Basic Research><Basic Science><Biology><Bronchial Asthma><C Fiber><CNS plasticity><COPD><Chemicals><Chronic><Chronic Obstruction Pulmonary Disease><Chronic Obstructive Lung Disease><Chronic Obstructive Pulmonary Disease><Clinical Research><Clinical Study><Coughing><Disease><Disorder><Dysfunction><Functional disorder><Funding><Grant><Human><Hyperactivity><Image><Infection><Inflammation Mediators><Inflammatory><Investigators><Laboratories><Life><Mentors><Methodology><Methods><Modern Man><Modernization><Nature><Nerve><Nerve Cells><Nerve Unit><Nervous System><Neural Cell><Neurobiology><Neurocyte><Neurologic Body System><Neurologic Organ System><Neuronal Plasticity><Neurons><Neurosciences><Neurosciences Research><Physiopathology><Play><Pulmonary Body System><Pulmonary Organ System><Research Personnel><Researchers><Respiratory System><Respiratory Tracts><Respiratory tract structure><Role><Secondary to><Slow-Reacting Substances><Sodium Channel><Sodium Ion Channels><System><Techniques><Technology><Viral Diseases><Virus Diseases><Visceral><adulthood><afferent nerve><airway epithelium inflammation><airway hyper-reactivity><airway hyperactivity><airway hyperreactivity><airway hyperresponsiveness><airway hypersensitivity><airway inflammation><central nervous system plasticity><chronic obstructive pulmonary disorder><critical period><cytokine><imaging><inflammatory mediator><innervation><interest><nerve supply><neural plasticity><neurobiological><neuronal><neurophysiological><neurophysiology><neuroplastic><neuroplasticity><new drug target><new druggable target><new pharmacotherapy target><new therapeutic target><new therapy target><novel drug target><novel druggable target><novel pharmacotherapy target><novel therapeutic target><novel therapy target><pathophysiology><respiratory><respiratory inflammation><respiratory tract inflammation><sensory nerve><slow reacting substance><social role><user-friendly><viral infection><virus infection><virus-induced disease><voltage>