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 tisses). 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), transfusion-related respiratory problems, sickle cell disease, and pulmonary hypertension of adults and newborns.
Funding: VA and NIH.
Education and Training
- Pulmonary Fellow, Medicine, Duke University, 1996 - 1999
- Medical Resident, Medicine, Duke University, 1993 - 1996
- M.D., Tulane University, 1993
- Ph.D., Tulane University, 1992
- Role of S-nitrosothiols in Akt1 signaling and pneumonia resolution
- Research Training in Allergy and Clinical Immunology
- Transfusion Medicine and Hematology
- Interdisciplinary Training Program in Lung Disease
- Hand-held advanced functional imager for assessing local tissue oxygenation
- S-nitrosothiols, NF-KappaB and Inflammation in Acute Lung Injury
- Sepsis-induced Red Cell Dysfunction (SiRD)