Massachusetts General Hospital

BiographyThe long-term goals of my laboratory are to explore the fundamental mechanisms of newborn lung injury and to develop novel therapies for pulmonary vascular disease.

Lung injury in children often causes abnormal pulmonary arterial vasoreactivity and muscularization. Through processes that are incompletely understood, many children with lung injury develop progressive and irreversible pulmonary hypertension, intra- and extra-pulmonary shunting of deoxygenated blood, and severe hypoxemia.

In early studies, we observed that low levels of inhaled NO rapidly cause pulmonary vasodilatation. Furthermore, the dilator effect of inhaled NO was limited to the lungs since it did not cause systemic vasodilatation. After evaluating the dose-response to inhaled NO in the laboratory and developing a safe NO delivery system, we performed the first clinical trials of inhaled NO in pediatric patients with pulmonary hypertension. Low levels of inhaled NO were observed to safely decrease hypoxemia and pulmonary hypertension in critically ill newborns with pulmonary vascular disease and intrapulmonary shunt. Subsequently, my laboratory led a prospective, randomized, placebo controlled, multicenter study that demonstrated that inhaled NO treatment decreases hypoxemia and the requirement for extracorporeal membrane oxygenation (ECMO) in newborns with pulmonary hypertension. These studies stimulated investigations of inhaled NO in the pediatric lung through out the world and were pivotal in the acceptance of inhaled NO by the Federal Drug Administration of the United States as a therapy for pulmonary hypertension and hypoxemia in newborns.

Research

Research Areas

• Novel mechanisms and therapies for pulmonary vascular disease in pediatric patients.
• Role of inhaled nitric oxide (NO) gas in preventing newborn lung diseases.
• Molecular mechanisms through which NO and cGMP regulate vascular smooth muscle cell differentiation and proliferation.   

Description of Research

My research focuses on discovering novel mechanisms and therapies for pulmonary
vascular disease in pediatric patients. My team's current work is directed at:

• examining the molecular mechanisms through which NO and cGMP regulate vascular smooth muscle cell proliferation and differentiation
• examining how cytokine neutralization may protect NO and cGMP signaling in models of pediatric chronic lung disease
• identifying novel signaling systems that contribute to the pathobiology of pulmonary hypertension in newborns and infants

My lab is in the Cardiovascular Research Center of Mass General Hospital.

PublicationsOver 60 publications