The broad focus of the Kourembanas laboratory is the elucidation of the vascular responses to hypoxia at the molecular, cellular, and organismal levels. Hypoxia increases the expression of heme oxygenase-1 (HO-1), a cytoprotective enzyme that degrades heme to generate carbon monoxide (CO, a vasodilating gas with anti-inflammatory properties), biliverdin (which is rapidly converted to the antioxidant bilirubin), and iron (sequestered by ferritin). HO-1 activity protects cells and tissues from hypoxia-induced injury, ischemia-reperfusion and the progression of vascular diseases due to inflammation and oxidative stress. Studies in the laboratory using HO-1 null (-/-) mice and transgenic mice with lung-specific constitutive and inducible HO-1 overexpression support this hypothesis. Whereas hypoxia causes severe pulmonary artery hypertension (PAH) with right ventricular dilatation, oxidative damage and infarction in mice lacking HO-1, mice with high lung HO-1 levels are protected from both lung and cardiac injury. Moreover, wild-type mice exposed to hypoxia develop marked lung inflammation with elevated expression of chemokines and cytokines, as well as neutrophil infiltration prior to the manifestation of PAH. Inhibition of early inflammation by transient, inducible, lung-specific expression of HO-1 prevents the later development of PAH. A central line of investigation in the laboratory is the study of the transcriptional and epigenetic mechanisms by which hypoxia induces chemokine gene expression leading to lung inflammation, and the mechanisms by which HO-1 activity resolves inflammation and inhibits the prohypertensive actions of hypoxia to maintain vascular homeostasis.
About Stella Kourembanas
Stella Kourembanas received her MD from New York University Medical Center. She completed pediatric residency at Massachusetts General Hospital and fellowship in Neonatal-Perinatal Medicine at the Harvard Joint Program in Neonatology, Children's Hospital Boston. She is the recipient of several teaching awards, including the Janeway Award for Excellence in Clinical Teaching at Children's Hospital Boston, and the Bernfield Award for Outstanding Contributions towards Fellows' Career Development from the Harvard Neonatal-Perinatal Fellowship.