Lung Injury Research
Preserving Epithelial Barrier Integrity in Ventilator Induced Lung Injury
We have a series of studies demonstrating the importance of considering not only the mechanical ventilation settings, but also how they impact the working subunits of the lung. A study was recently concluded investigating the impact of time and energy dissipation on evolving lung injury with Professors Jason Bates (University of Vermont) and Don Gaver (Tulane University) [Ramcharran J Appl Physiol 2022]. The next set of studies is a continuation of this work and will focus on understanding the epithelial injury that occurs with mechanical ventilation and establishing biopredictors of damage and recovery from ventilator induced lung injury in an acid-aspiration model.
Funded by NIH 2 R01 HL142702-05
Novel Therapeutic Approach for Severe ARDS with a Potent Pharmacologic Allosteric Hemoglobin Modifier
This is also a joint-industry project (funded by a Phase II) with Illexcor that is looking at a drug that can allosterically modify hemoglobin to improve oxygen offloading. It has been studied for use in patients with sickle cell disease and we are determining if it can serve a dual purpose by improving oxygenation in patients with lung injury. This study will also be using the 6-hour lung injury model.
Lungs that are severely injured are not able to participate effectively in oxygen and carbon dioxide exchange. One therapeutic option is to increase the oxygen concentration administered, however this can itself be damaging, and there is a limit to how much support this provides. Critically ill patients are therefore at risk of hypoxia where organs have insufficient oxygen to function optimally and are vulnerable to injury. I am working with Dr. Osheiza Abdul-Malik (University of Pennsylvania) who has developed a drug (IEX-039.glycine) that allosterically modifies hemoglobin to increase the capacity to bind and transport oxygen. I have developed a model of lung injury with intratracheally instilled endotoxin and am using this to test the efficacy of IEX-039.glycine on reducing hypoxia.
Funded by NIH 2 R44 HL156334-02