Biomedical Research Funded in 2002

1) Jeanine Wiener-Kronish, MD, University of California San Francisco, San Francisco, California, Principal Investigator and Britta Swanson, PhD, Post Doctoral Fellow

"Lung Infection and Biofilms of P. aeruginosa"

In this study, efforts were made to develop new agents to thwart P. aeruginosa infection

in CF patients. The particular class of agents that were focused on were those that inhibit

bacterial adhesion. Results showed that when the adherence of wild-type PAK was

compared to a PAK pilin mutant, there was a three-fold decrease in adherence over a wide

range of bacterial concentrations. Additional studies are currently being done to analyze

bacterial inhibition by the addition of various carbohydrates to the adhesion assay. These

carbohydrates could potentially block adherence. Future plans include analyzing the

adherent properties of other bacterial species.

Amount Funded: $17,500.00

2) Horst Fischer, PhD, Children’s Hospital Oakland Research Institute, Oakland, California, Principal Investigator

"Image Processing Hardware and Software Upgrade"

The purpose of this grant was to fund the equipment upgrade of an existing patch clamp

system that allows simultaneous measurement of proton currents across the cell membrane

and associated changes in intracellular pH. This equipment will aid in determining why the

airway surface liquid (ASL) is acidic. Such increased acidity found in CF patients is

detrimental for normal airway functioning.

Amount Funded: $22,000.00

3) Martin Kharzzi, PhD, California Department of Health Services, Principal Investigator and

Michelle Pearl, PhD, Research Scientist

"AFP Levels in Newborns with Cystic Fibrosis"

Funding was provided to look into the current screening models of newborns for CF.

Researchers found that approximately 10% of all CF cases were missed with current

models. Efforts are now being made to improve case detection, including search for a third

marker of the CF disease. The current investigation evaluates whether the measurement of

AFP levels in newborn blood spots improves case detection and specificity within the high-

immunoreactive trypsinogen (IRT) group. Results show that adding AFP to the newborn

screening protocol unfortunately will not improve specificity while preserving sensitivity. It

may, however, be useful for other purposes, such as a prognostic indicator of disease

severity.

Amount Funded: $27,000.00

4) Marybeth Howard, PhD, University of California San Francisco, San Francisco, California, Principal Investigator

"Effect of S-Nitrosogluatathione on Delta 508 Folding/Function"

This purpose of this study is to find a pharmacological approach to correct the misfolding

of Delta F508 CFTR, leading to a therapeutic cure for CF. The compound to be investigated

is S-Nitrosogluatathione, a naturally occurring antioxidant found in the airway epithelial fluid.

This potentially could relax airway smooth muscle, improve ciliary movement which would

improve mucous clearance, and it has antimicrobial activity as well as other beneficial effects.

Amount Funded: $11,000.00