Treatment-related biomarkers in pulmonary hypertension patients on oral therapies.

Statistical methods in clinical trials, survival analysis, adaptive designs, adaptive treatment strategies, causal inference in observational studies, semiparametric inference

Duke University Medical Center
Duke Clinical Research Institute

The McMahon Lab at Duke University and Durham VA Medical Center is investigating novel roles of the red blood cell (RBC) in the circulation. The regulated release of the vasodilator SNO (a form of NO, nitric oxide) by RBCs within the respiratory cycle in mammals optimizes nutrient delivery at multiple levels, especially in the lung (gas exchange) and the peripheral microcirculation (O₂ transport to tissues). Deficiency of RBC SNO bioactivity (as in human RBCs banked for transfusion), for example, appears to contribute to the serious lung and circulatory problems associated with RBC transfusion in some settings. We have also demonstrated benefit in the use of treatments that exploit RBCs as a vehicle for delivery of SNOs, in both human patients and in model animals.

RBCs also release ATP in response to stimuli including deformation and hypoxia, and the exported ATP also participates in the maintenance of a healthy circulation, according to mechanisms that we are now unraveling.

We use basic and translational approaches to understand the molecular mechanisms by which these RBC-derived signals effect circulatory changes in human health and disease, particularly in the lung. Disease states driving this research include acute and chronic lung diseases such as sepsis (severe infection, such as COVID-19), transfusion-related respiratory problems, sickle cell disease, and pulmonary hypertension of adults and newborns.

Funding: VA and NIH.