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Enzyme necessary for development of healthy immune system
Date:12/22/2009

id the research team expected to find widespread defects in development when they knocked out the dCK enzyme in the mice.

"Surprisingly, we found that the gene had a highly specific role in the development of organs crucial to a normally-functioning immune system," Austin said. "Mice lacking the dCK enzyme have thymuses that are reduced in size by 90-fold. That defect in thymus size resulted in mice having 5 to 13-times fewer lymphocytes circulating throughout the body."

This finding is part of research that was launched several years ago and represents the third significant discovery. The first was the development of a new probe for PET scanning created by modifying a common chemotherapy drug, an advance that allowed UCLA researchers to model and measure the immune system in action and monitor response to new therapies.

Researchers created the molecule, called FAC, by slightly altering the molecular structure of gemcitabine, a chemotherapy drug that is activated by dCK activity. They added a radiolabel so the cells that take in the probe can be seen during PET scanning.

The probe was based on a fundamental cell biochemical pathway called the DNA Salvage Pathway, which includes dCK. All cells use this biochemical pathway to different degrees. But in lymphocytes, which are the active players in the adaptive immune system, the pathway is activated at very high levels. Because of that, the probe accumulates at high levels in those cells, said Dr. Owen Witte, director of the Broad Stem Cell Research Center and a Howard Hughes Medical Institute investigator.

That work was published June 8, 2008 in the journal Nature Medicine.

The second significant finding was the development of a non-invasive approach that may allow doctors to evaluate a tumor's response to a drug before prescribing the treatment, enabling physicians to personalize therapy to the patient's unique biochemistry.

In this study, the U
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Contact: Kim Irwin
kirwin@mednet.ucla.edu
310-206-2805
University of California - Los Angeles
Source:Eurekalert

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