Diverse Cardiopulmonary Diseases are Associated with Distinct Xenon MRI Signatures.

Duke University Medical Center
Duke Clinical Research Institute

Our research focuses on magnetic resonance imaging (MRI) research with hyperpolarized 129Xe gas. We are at at the forefront of developing this novel technology for imaging the lungs of patients with pulmonary disease. We currently have multiple, ongoing NIH and industry-sponsored studies invovling this technique. Hyperpolarization is a laser-based process that enhances the MRI signal of xenon gas by a factor of 100,000 to allow for high-resolution, non-invasive MRI of pulmonary function. In addition to our research program, this technology was recently FDA approved and efforts are underway to implement it clinically.

Current studies are applying 129Xe MRI for early diagnosis and monitoring of interstitial and pulmonary vascular diseases. Our group, which is comprised of MRI scientists and radiologists, works closely with colleagues in pulmonary medicine. Our laboratory provides research opportunities to Ph.D., Masters, and medical students as well as select undergraduate students. 

I am a physician-scientist with a research focus on G protein-coupled receptor signaling in inflammation and vascular disease and a clinical focus on pulmonary vascular disease, as I serve as Co-Director of the Duke Pulmonary Vascular Disease Center. My research spans the spectrum from clinical research in pulmonary vascular disease, to translational research in cardiovascular disease, to the basic science of receptor signaling. 

Our basic science resesarch focuses on understanding and untapping the signaling potential of G protein-coupled receptors (GPCRs) to regulate inflammation in vascular disease. GPCRs are the most common transmembrane receptors in the human genome (over 800 members) and are some of the most successful targets for drug therapies. While it has been known for some time that these receptors signal through multiple downstream effectors (such as heterotrimeric G proteins and multifunctional beta arrestin adapter proteins), over the past decade it has been better appreciated that these receptors are capable of signaling with different efficacies to these effectors, a phenomenon referred to as “biased agonism”. Ligands can be biased, by activating different pathways from one another, and receptors can be biased, by signaling to a limited number of pathways that are normally available to them. Moreover, this phenomenon also appears to be common to other transmembrane and nuclear receptors. While a growing number of biased agonists acting at multiple receptors have been identified, there is still little known regarding the mechanisms underlying biased signaling and its physiologic impact.

Much of our research focuses on the chemokine system, which consists of approximately twenty receptors and fifty ligands that display considerable promiscuity with each other in the regulation of immune cell function in inflammatory diseases. Research from our group and others have shown that many of these ligands act as biased agonists when signaling through the same receptor. We use models of inflammation such as contact hypersensitivity and pulmonary arterial hypertension (PAH). PAH is a disease of the pulmonary arterioles that results in right heart failure and most of its treatments target signaling by GPCRs. We use multiple approaches to probe these signaling mechanisms, including in-house pharmacological assays, advanced phosphoproteomics and single cell RNA sequencing.