Andreas Schwingshackl, M.D, Ph.D.

Andreas Schwingshackl, M.D, Ph.D.

Institution: University of California, Los Angeles

Project: TREK-1 potassium channels protect from ventilator-induced lung injury

Grant(s): Innovation Award

All patients with respiratory failure are treated with oxygen therapy and mechanical ventilation, although both therapies promote further lung injury and may increase patient death rates. Doctors try to limit the degree of oxygen and mechanical ventilation exposure but have not been able to eliminate the injurious consequences of these therapies. Currently, no targeted approaches exist to counteract such injury. In our lab, we discovered that oxygen therapy and mechanical ventilation decrease the levels of proteins called TREK-1 potassium channels in the lung, which accelerates further injury. In this study, we will study the mechanisms underlying TREK-1-mediated protection and determine whether activation of residual TREK-1 channels with newly developed pharmacological compounds can counteract oxygen and mechanical ventilation-induced lung injury. We will also introduce two novel, next-generation devices to mimic these injurious events occurring in the lung.

Update:

Over the past year, we accumulated strong evidence that once-daily treatment of mice or human lung cells with highly specific TREK-1 channel activating compounds can protect against oxygen- and mechanical ventilation-induced lung damage. We are also in the early stages of implementing for the first time two next generation devices to mimic this type of lung injury, which allows us to better define the specific mechanisms underlying oxygen- and mechanical ventilation-induced lung injury and facilitate drug development.

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