Duquesne Researcher Developing Compounds to Battle Fatal Infections with $1.9 Million NIH Grant
Where others see infection, Dr. Aleem Gangjee sees a travesty waiting to happen.
Gangjee, Distinguished Professor in Duquesne University's Mylan School of Pharmacy, knows far too much about the patients who beat cancer or HIV or survive a transplant, only to succumb to a simple infection that turns deadly because of their compromised immune systems.
A medicinal chemist best known for his cancer research, Gangjee has received a $1.9 million, five-year award from the National Institute of Allergy and Infectious Diseases, an arm of the National Institutes of Health (NIH), to develop compounds that show promise of defeating the stubborn fungal infections that can further sicken or claim the lives of immune-compromised patients.
Gangjee and his collaborators at the Hauptman-Woodward Medical Research Institute, University of Cincinnati and Indiana University are targeting a specific enzyme in pneumocystis jirovecii (pronounced jir-o-VESS-ee-eye), which is critical for synthesizing DNA. Because the fungus grows only in the human lungs, the researchers face special challenges.
The fungus can't be grown in a petri dish culture. Only in 2002 did scientists learn that the fungus, when introduced in animals, adapts to the specific animal; for instance, in rats, the 3-D shape of the fungus enzyme is 30 percent different from that of the human fungus enzyme.
But, Gangjee said, Hauptman-Woodward collaborators have managed to splice an extract of the enzyme's DNA into insects, which grow it unaltered from the human strain. Gangjee then took a page from his cancer research book and, with his University of Cincinnati collaborator, engineered a method of culturing the enzyme in a hollow fiber that can be implanted without changing the fungus and fearing rejection.
"We still don't know the 3-D shape of the fungus, but we now have compounds that are very, very highly effective for this fungus enzyme, about 99- to 100-fold effective," said Gangjee, who aims to improve this effectiveness to 1,000 fold for even greater therapeutic advantage.
Not only do Gangjee's compounds work specifically on the human fungus enzyme, they remain effective against the top strains of the infection that resist current treatments.
To learn more about Gangjee's work, visit http://newsroom.duq.edu/2011/04/06/cancer-killing-compounds-developed-at-duquesne-attract-national-attention-with-2-8-million-grant/
Watch his video explaining how important the shape of tumor-killing compounds is: http://newsroom.duq.edu/2011/09/01/amazing-chemistry-tricks-cancer-cells/