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Our work is focused on the translational human in vivo and ex vivo assessments of right ventricular (RV) function in the setting of pulmonary hypertension.
Among patients with group I pulmonary arterial hypertension PAH, those with systemic-sclerosis-associated PAH (SSc-PAH) have a particularly poor prognosis and less optimal response to PAH-guided therapy. Using in vivo pressure-volume catheterization of the right ventricle, we have uncovered key deficiencies in resting and reserve RV function in the SSc-PAH group when compared to idiopathic PAH (IPAH) patients. These studies have uncovered key discoveries with regards to right ventricular-pulmonary arterial (RV-PA) coupling in PAH. In the lab, by studying myofilament function from RV endomyocardial biopsies from these same patients, we have uncovered corresponding deficiencies in myofilament contractility and calcium sensitivity as well. Ongoing work is directed towards determining the underlying mechanism of these findings, which... will hopefully lead to therapeutic applications for RV failure in SSc-PAH.
Further endeavors are directed towards studying RV failure in other populations, including exercise-induced PH, PH secondary to left-heart disease, and the left ventricular assist device population. view more
James Sham Lab
Research in the James Sham Lab focuses on pulmonary arteries. Studies include local calcium signaling in the pulmonary arteries and transient receptor potential (TRP) channels in pulmonary arterial smooth muscle cells. We’re also interested in calcium regulation in chronic hypoxic pulmonary hypertension.
Basic science investigations span an array of inquiries, such as understanding the basic mechanisms underlying cardiac dyssynchrony and resynchronization in the failing heart, and beneficial influences of nitric oxide/cGMP/protein kinase G and cGMP-targeted phosphdiesterase signaling cascades on cardiac maladaptive stress remodeling. Recently, the latter has particularly focused on the role of phosphodiesterase type 5 and its pharmacologic inhibitors (e.g. sildenafi, Viagra®), on myocyte signaling cascades modulated by protein kinase G, and on the nitric oxide synthase dysregulation coupled with oxidant stress.
The lab also conducts clinical research and is presently exploring new treatments for heart failure with a preserved ejection fraction, studying ventricular-arterial interaction and its role in adverse heart-vessel coupling in left heart failure and pulmonary hypertension, and testing new drug, device, and cell therapies for heart disease. A major theme has been with the use ...of advanced non-invasive and invasive catheterization-based methods to assess cardiac mechanics in patients.asive and invasive catheterization-based methods to assess cardiac mechanics in patients.
David Kass, MD, is currently the Director at the Johns Hopkins Center for Molecular Cardiobiology and a professor in cellular and molecular medicine. view more
Research in the Kazuyo Yamaji-Kegan Lab seeks to better understand the mechanisms, regulation and functional outcomes of a patient’s Th2 immune response during the development of pulmonary hypertension. Our team has demonstrated a direct connection between Th2 cytokine interleukin (IL)-4 and pulmonary vascular growth response; we’re now exploring the mechanisms of endothelial cell injury and subsequent Th2 immune response as it relates to cardiopulmonary diseases. In addition, we are researching pulmonary vascular angiogenesis, vasculogenesis and inflammation using in vivo physiology, in vitro cell biology, and genetic and biochemical methodology.
Larissa Shimoda Lab
Research in the Larissa Shimoda Lab focuses on several important topics within pulmonary and critical care medicine. We primarily study pulmonary arterial responses to chronic hypoxia as well as hypoxic pulmonary vasoconstriction and oxidant-mediated lung injury. Our recent research has included investigating the effects of chronic hypoxia on pulmonary circulation and the ways in which hypoxia-inducible factors impact pulmonary vascular responses to hypoxia. We have also studied vascular remodeling in patients with pulmonary hypertension.
Stephen Mathai Lab
The Stephen Mathai Lab focuses its research on pulmonary medicine. We're particularly interested in scleroderma-associated pulmonary hypertension, pulmonary complications of connective tissue disease, idiopathic pulmonary fibrosis and pulmonary hypertension.