The Research Institute at Nationwide Children's Hospital - Louis Chicoine, M.D. Profile
Louis Chicoine, M.D.
photo of Louis Chicoine, M.D.

LAB DESCRIPTION

BIOGRAPHY

PUBLICATIONS
Gene Therapy

PRINCIPAL INVESTIGATOR

Louis.Chicoine@
nationwidechildrens.org

The Research Institute at Nationwide Children's Hospital
700 Childrens Drive
Columbus, OH 43205
p: 614.722.2678 | f: 614.722.3273

CHICOINE LABORATORY
Our lab is focused on the study of normal and abnormal lung and lung vascular development.  Successful transition from the high resistance fetal pulmonary circulation to the low resistance postnatal pulmonary circulation involves a shift in the balance between vasoconstriction and vasodilation. Pulmonary endothelial nitric oxide synthase (eNOS) is an important source of the endogenous vasodilator nitric oxide (NO). Changes in eNOS may activity be an important contributor to the decrease in pulmonary vascular resistance normally seen after birth.  Several ongoing studies using models ranging from cell culture to isolated lung, and techniques ranging from RNA interference to physiological studies are directed at answering questions relating eNOS expression and NO production, and their affect on pulmonary artery tone during development.
 
Under certain conditions this normal progression from the high resistance pulmonary arteries of the fetus to the low resistance pulmonary arteries of the neonate fails, causing persistent pulmonary hypertension of the newborn (PPHN).  PPHN continues to have high morbidity and mortality despite advances in neonatal intensive care.  The hallmark of PPHN is abnormally constricted and thickened pulmonary arteries.  Several poorly understood mechanisms are likely responsible for these changes that include smooth muscle cell migration, proliferation, and hypertrophy.  Current treatment modalities are often of limited value and are associated with high degrees of morbidity.  With its anti-mitogenic and vasodilatory properties, alterations in pulmonary NO production are key in the pathogenesis of PPHN.  Clinical trials using inhaled NO for the treatment of PPHN demonstrated limited efficacy with a failure rate of between 40 and 50%. Gene therapy using inducible NO synthase (iNOS) directed at the lung might be expected to decrease pulmonary vascular resistance and arrest pulmonary vascular remodeling associated with PPHN, and be safer and more efficacious than inhaled NO therapy.  Therefore, we are currently utilizing a neonatal rat model of pulmonary hypertension to study the effects of gene therapy with iNOS on pulmonary vascular reactivity and remodeling, as well as any potential toxicities of iNOS gene therapy.  These studies are the first step in providing more effective and safer treatment to babies born with PPHN cared for in the neonatal intensive care unit.