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Studies

Oxidative Stress Mechanisms & Clinical Effects Group

The Oxidative Stress Mechanisms & Clinical Effects Group conducts several ongoing research projects within the Clinical Research Program.

Susceptibility to Oxidative Stress: SNPs, Gene Expression, Neonatal Oxygen Risk
PI: Douglas A. Bell, PhD. The overall objective of this project is to test the hypothesis that oxidative stress gene expression profiles and genetic variation (e.g. SNPs, insertions, deletions) predict risk for oxygen-induced lung disease in neonates and therefore may be important in the pathogenesis of other oxidant-related diseases.

Positional Cloning of Oxidant Susceptibility Genes in Mice
PI: Steven R. Kleeberger, Ph.D. The overall objective of this project is two-fold: 1) to determine the genetic mechanisms of differential susceptibility to hyperoxic lung injury in adult and neonatal inbred mice, and 2) utilize genetic information to determine whether functional polymorphisms in candidate genes associate with protect against chronic lung disease in high-risk neonates and other oxidant-related diseases.

Role of Mitochondrial Reactive Oxygen Species in Hyperoxia-induced Tissue Injury
PI: Bennet Van Houten, PhD. The overall objective of this project is to examine hyperoxia-induced-ROS stress responses and subsequent DNA damage in the mitochondria and the nucleus, in yeast, C. elegans, and human cells; and will test the hypothesis that the main source of ROS is generated in the mitochondria of epithelial cells. It will also validate mtDNA damage as an early biomarker of disease associated with oxidant stress.

Candidate Susceptibility Gene Function in Lung Oxidative Stress Damage
PI: Richard S. Paules, Ph.D. The overall objective of this project is to determine the molecular signaling function of key susceptibility determinant genes in cellular damage responses to hyperoxia that can protect against lung injury, using both human lung epithelial cell cultures and newborn mice deficient in certain key candidate genes.

Oxidant Susceptibility Genes and Neonatal Diseases Associated with Hyperoxia
PI: Fernando Polack, M.D. The overall objective of this project is to establish a prospective cohort of case-parent triads selected for very low body weight (VLBW) infants and parental controls in a hospital network in Argentina to examine the role of candidate antioxidant genes in susceptibility to bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP).

Human Airway Gene Profiling Core
PI: Michael B. Fessler, M.D. This core will interface with Program investigators to profile gene expression from respiratory epithelium and airspace cells of human subjects affected by a variety of environmental airways diseases, and from subjects exposed to controlled inhalants (e.g. ozone, hyperoxia, lipopolysaccharide).

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