Cincinnati--Melanie T. Cushion, PhD, associate professor, University
of Cincinnati (UC) Department of Internal Medicine, Division of
Infectious Diseases, together with George Smulian, MD, Internal
Medicine, and James Stringer, PhD, Department of Molecular Genetics, is
leading an international, multiple-center research project to develop
new drug targets for a major AIDS-related pathogen, Pneumocystis carinii.
Pneumocystis Genome Project" is a $2,889,682 grant funded by the
National Institute of Allergy and Infectious Diseases. The five-year
genomics-related research grant will complement the UC Medical Center's
new core facilities for genomics, proteomics and bioinformatics.
Scientific evidence indicates that Pneumocystis appears to exist in
mammals with intact immune systems, but without indication of clinical
symptoms. However, once the host immune system becomes suppressed by a
viral infection, such as HIV, or drug therapy to prevent organ
rejection, these organisms are able to grow and fill the lungs and are
likely to cause lethal pneumonia. Pneumocystis cannot survive outside
the mammalian lung for any length of time, so little is understood
about its life cycle.
"We hope to better understand this
pathogen's basic biology by looking at its genetic makeup and how it
infects the mammalian host," Cushion said. "We also hope to understand
why it won't grow outside the lung, and if there is something we can
add to an artificial medium that will permit it to do so." By knowing
all of its genes and metabolic pathways, researchers can design novel
drugs for therapy and treatment.
"Only two drugs are highly
effective against Pneumocystis pneumonia," she said.
"Trimethoprim-sulfamethoxazole and pentamidine, and each has serious
side effects. Moreover, there is increasing evidence that Pneumocystis
is becoming resistant to both, as well as other secondary therapies."