Ben M. Dunn, Ph.D.
Drug Discovery against Infectious Organisms
The DUNN laboratory clones and expresses enzymes from pathogenic organisms so that the protein may be used as a target for drug design and discovery. In addition, we also study human enzymes to insure that the new compounds do not inhibit the host systems. We are funded by NIH to study variants of the HIV-1 protease arising from the different subtypes that are found around the world. All the drug discovery and all the clinical trials to date have been done using subtype B virus, which only accounts for about 8 % of the HIV-1 infections around the world. We are studying subtype A and C, which together account for about 75 % of infections. We have expressed the subtype C virus protease and crystallized it alone and in combination with several inhibitors. We also make mutants to test the effects upon drug binding.
We also study plasmepsins, enzymes from the malarial parasite, Plasmodium falciparum, as targets for new drug discovery. We are currently focused on plasmepsins 9 and 10, which are expressed in the blood stage of the malarial life cycle, but which have unknown function. Inhibitors of these enzymes kill the parasite in culture. We have also designed, synthesized and studied new inhibitors in complex with plasmepsins.
A third current project is the protease of the HTLV-1 virus. This is known to cause leukemia in some patients and could be an attractive target for drug discovery due to similarities to the HIV-1 enzyme. However, the specificity of the HTLV-1 protease is different, thus requiring new inhibitor design/discovery.
We are also using computational methods to screen libraries of compounds to seek new inhibitor structures for all three systems.
Possibly Accepting New Students This Year
office: ARB R3-226A
lab: ARB R3-187, R3-191
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Professor Dunn received his B.S. in chemistry from the University of Delaware in 1967 and the Ph.D. in Bio-organic Chemistry in 1971 from the University of California at Santa Barbara. He joined the faculty of the Department of Biochemistry & Molecular Biology in 1974 and rose through the ranks to become a Professor in 1988. He received the title of Distinguished Professor in 1998. His research interests include protein structure and function, especially for proteolytic enzymes of infectious organisms that are targets for drug design and discovery. His laboratory currently works on HIV-1 protease from several subtypes found around the world, on enzymes from the malarial parasite, Plasmodium falciparum, and the protease from the HTLV-1 virus. He also has interests in organisms known to cause opportunistic infections in patients whose immune systems are compromised due to chemotherapy or viral infections, such as the tuberculosis bacteria and Candida albicans.
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