) The candidate, an M.D., Ph.D. board eligible in Pulmonary and Critical Care Medicine, is strongly committed to a career in academic medicine with an emphasis on the molecular biology of lung injury and the development of strategies for gene therapy of lung disease. With the aid of this grant, he plans to develop further expertise in molecular biology and gene therapy techniques under the supervision of leaders in these fields. With the benefit of this experience, the candidate plans to establish himself as an independent investigator pursuing basic research, while keeping an active role in the practice of pulmonary medicine. The candidate proposes to study the role of perfluorocarbons (PFC) in augmenting gene delivery to lung. PFC are short fluorinated carbon chains with remarkable properties of gas solubility that can support effective gas exchange when instilled into the lung. PFC use provides a novel means of augmenting distribution of intratracheally co-administered drugs. A single recent report suggest that PFC may improve distribution of intratracheally administered adenoviral-vectors for gene transfer. Recent observations suggest the PFC can inhibit activity of macrophages and neutrophils following in vitro exposure. Using a model of PFC use in spontaneously breathing rodents, developed by the applicant, the role of PFC in augmenting gene delivery to lung will be investigated. The central hypothesis is that PFC use results in more widespread and uniform distribution, and in higher level of transgene expression.
The specific aims are: 1) To evaluate PFC effect on adenoviral and liposomal-mediated transgene delivery to lung. 2) To investigate potential anti-inflammatory effects of PFC instillation in the lung. These studies are expected to help clarify the effects of PFC in augmenting gene delivery to lung and to evaluate possible anti-inflammatory effects of PFC instillation on gene delivery to lung. The long-term goal is to establish the scientific basis for therapeutic approaches using PFC in augmenting gene transfer to lung.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
1K08HL003864-01
Application #
2671052
Study Section
Special Emphasis Panel (ZHL1-CSR-Y (M2))
Project Start
1998-07-10
Project End
2003-06-30
Budget Start
1998-07-10
Budget End
1999-06-30
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
075524595
City
Seattle
State
WA
Country
United States
Zip Code
98109
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