The current research interests of Institute investigators encompass both basic and applied biomedical studies with special emphasis on undersea and aerospace environments and on the interface of the environment with the respiratory and nervous systems. Their research programs are oriented toward the following environmentally-relevant problems.

• The pathophysiology of oxygen toxicity and strategies
to increase pulmonary and central nervous system tolerance
to oxygen at high pressure.

• Prevention of brain injury and delayed sequelae associated with carbon monoxide poisoning.

• The mechanisms for adaptation to acute hypoxia.

• Regimens for prevention and treatment of decompression sickness in divers and astronauts.

• The basis for treatment of infants or adults with respiratory distress syndrome.

Program in Cellular and Molecular Biology of the Lung
A. Fisher, Program Leader

This program investigates basic processes in the function of lung epithelium and metabolism of lung surfactant. Emphasis is on lipid and protein synthesis, and on secretion, reuptake, and intracellular processing of surfactant using isolated cell and intact lung systems. Funding is primarily by a Program Project grant from NHLBI with participating investigators from the departments of Physiology, Medicine, and Pediatrics.
Program research areas and investigators:

Exo/Endocytosis and Phospholipid Metabolism 
Fisher, Shuman, Bates, Zimmerman

• Uptake and recycling of surfactant by pulmonary epithelium.
• Cell membrane receptors for surfactant proteins.
• Biochemistry and function of lung phospholipase A2.
• Fusinogenic proteins and proteolysis in lamellar body exocytosis.

Processing of Surfactant Associated Proteins 
Beers

• Synthesis and processing of hydrophobic surfactant proteins.
• Characterization of surfactant proteins in alveolar proteinosis.

Mechanisms of Gene Expression
Feinstein

• Promoter mapping of genes for lung surfactant apolipoproteins.
• Transcription factors for surfactant-associated protein gene promoters.

Lung Development
Ballard

• Glucocorticoid regulation of surfactant protein synthesis.
• Gene expression in human fetal epithelium.

Intercellular Communication
Koval

• Identification of connexins in lung cells.

Center for Hyperbaric Oxygenation Therapy
S. Thom, Center Leader

This program is oriented toward understanding the role of hyperbaric oxygen therapy and indications for treatment of patients. Special emphasis is directed towards the pathophysiology and mechanisms for CO poisoning. Current clinical trials include patients with CO exposure and patients with chronic radiation cystitis. Participating investigators are from departments of Emergency Medicine, Physiology, and Pediatrics, and the Institute's clinical staff. Funding is primarily by grants from NIEHS and private foundations.

Program research areas and investigators:

Mechanisms of CO Toxicity
Thom, Ischiropoulos

• Mechanisms of CO-mediated vascular stress.
• Leukocytes and amplification of brain injury in CO poisoning.

Oxygen Transport and Oxidative Metabolism
Buerk

• Simultaneous measurement of tissue PO2, nitric oxide and blood flow in the optic nerve.

Hyperbaric Oxygen Therapy: Clinical Trials
Thom, Clinical Staff

• Hyperbaric oxygen therapy and delayed sequelae of CO poisoning.
• Clinical trials for radiation cystitis.

Environmental Biomedical Stress Data Center

C. Lambertsen, Center Leader

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This program is oriented toward study of the physiology and pathophysiology of oxygen at concentrations below and above the normal. The program incorporates the Environmental Biomedical Research Data Center, a repository for data related to diving medicine and hyperbaric oxygenation therapy. Participating investigators are from the departments of Pharmacology and Anesthesiology. Funding is by grants from the US Navy (NMRDC), NASA and NOAA.

Program research areas and investigators:

Tolerance to Hypoxia and Hyperoxia
Lambertsen, Clark, Gelfand

• Use of CO2 in humans to accelerate CNS adaptation to hypoxia.
• Effects of CO2 and exercise in humans on CNS tolerance to hyperoxia.

Environmental Biomedical Research Data Center
Lambertsen, Flynn

• Incorporation of oxygen tolerance and decompression research data for use in the prevention and therapy of decompression sickness.
• Aid to national and international laboratories and agencies in development of undersea and aerospace decompression methods, using computer programs and analysis procedures developed by the Data Center.

Center for Research in Acute Lung Injury
A. Fisher, Center Leader

The focus for this program is mechanisms for lung injury with emphasis on the Acute Respiratory Distress Syndrome (ARDS). There is special interest in the initiation of lung injury due to oxidation events and the development of assays for early detection. The program incorporates a registry for ARDS patients. Funding is primarily by R-01 grants from NHLBI. Participating investigators are from the departments of Physiology, Pharmacology and Medicine.

Program research areas and investigators:

Lung Ischemic Injury
Fisher, Al-Mehdi

• Mechanisms of oxidative injury in ischemia-reperfusion.
• NADPH oxidase and endothelial ROS generation.

Biomarkers of Oxidant Stress
Ischiropoulos

• Serum protein oxidation and nitration in RDS.
• Oxidation of mitochondrial DNA.
• Peroxynitrite and apoptosis.

Immunotargeting and Antioxidant Defenses
Muzykantov

• Targeting of antioxidants to pulmonary endothelium using immunochemical methods.
• Targeting of glucose oxidase as a model of lung endothelial oxidative injury.

Fc gamma Receptors
Schreiber

• Induction of Fc gamma receptors in ARDS.
• ROS production by PMN.

Surfactant in Acute Lung Injury
Beers

• Metabolism of surfactant in pneumocystis carinii pneumonia