Developing a novel in utero gene therapy for cystic fibrosis (CF) is the goal of a research project that has led to a prestigious award for Suparna Mishra, a Keck School of Medicine postdoctoral fellow.
Mishra has been selected to receive a Medical Research Fellowship for up to three years from the A. P. Giannini Foundation. Her fellowship is one of only seven being awarded for 2009.
CF is the most common genetic disease in the United States, affecting one out of 2,500 live births per year. CF is caused by mutations in the CFTR gene, which leads to an ion/water imbalance in the lungs, intestines and other organs, Mishra explained. Consequently, sticky mucus blocks the lungs and intestinal tract, leading to chronic infections and malnutrition.
There is no cure for CF, and patients have an average lifespan of 36 years. The main cause of mortality is lung failure. However, Mishra said, it has been determined that as little as 5 percent correction of the mutated CFTR gene can restore the ion/water balance.
Mishra works in the division of immunology/bone marrow transplant at Childrens Hospital Los Angeles in the laboratory of Carolyn Lutzko, assistant professor of pediatrics. Lutzko’s laboratory has developed a system in which a ‘test’ gene can be transferred to the lung and intestine of a normal mouse fetus. They have found that after birth, up to 14 percent of the epithelial cells in the mouse’s lung have the ‘test’ gene.
Mishra aims to use this approach to evaluate whether transferring the normal CFTR gene to mouse fetuses with CF can prevent the development of CF disease. These studies may be able to provide the important proof-of-principle for novel in utero therapy for CF in humans.
It has been 20 years since USC last garnered one of the Giannini Medical Research Fellowships. Each year the A. P. Giannini Foundation invites promising young postdoctoral investigators in the early stages of their careers to apply to the program. Out of a large number of initial applicants, the foundation invited 19 candidates for interviews. Based on a presentation about her research, Mishra received a top ranking.
The foundation, formerly the Giannini Family Foundation, was established in 1945 by A. P. Giannini, founder of the Bank of America. Since 1951, the foundation has awarded 600 fellowships to postdoctoral biomedical researchers at California’s eight accredited medical schools.