Drug Development

• Jürgen Bosch and his team are exploring the structures of malarial proteins related to host-cell invasion and egress as well as to processes involved in the conversion of liver stage sporozoites into blood stage merozoites. The Bosch lab's ultimate goal is to apply structure guided drug design methods to identify small molecule inhibitors of the protein-protein interactions involved in these processes.
  
  
• Drug resistance is a major problem in the treatment of malaria and Ernesto Freire's laboratory is working on the development of new strategies in which drug molecules are conferred with adaptive properties that allow them to maintain efficacy in the face of naturally existing polymorphisms and mutations associated with drug resistance. To this end, they are successfully targeting the development of plasmepsin inhibitors. These inhibitors have been successfully tested in enzyme inhibition assays and their parasite killing ability has been confirmed in malaria infected red blood cells. 
  
  
• Myaing Nyunt, focuses on clinical studies of antimalarial and antiretroviral drugs, in both domestic and international settings, with a special interest in pregnant women.  She is planning to assess the pharmacokinetics and pharmacodynamics of artemether-lumefantrine in West African pregnant women living with HIV.
  
  
• The research groups led by Gary Posner and Theresa Shapiro are developing new antimalarial drugs based on the biological and chemical mechanisms of artemisinin, a Chinese herbal remedy for malaria. Recent advances include successful developing of single low oral dose cures of malaria-infected rodents. Dr. Shapiro is also working to determine the ideal pattern of antimalarial drug concentrations over time for established antimalarials and to exploring concentration time requirements for antimalarial drugs in combinations.
  

• Sean Prigge is focusing his research on essential metabolic pathways in the malaria parasite, particularly those required for the biosynthesis and modification of fatty acids.  Several enzyme cofactors such as pantothenate, lipoic acid, biotin and iron-sulfur clusters should be required for these metabolic pathways.  We are interested in these cofactors, how they are acquired, how they are used, and whether they are essential for the growth of malaria parasites. 
   
• David Sullivan and his team are investigating how current malaria drugs like chloroquine inhibit heme crystallization to kill the parasite.  The team is also exploring new uses of existing FDA-approved drugs for antimalarial action.
  
  David Sullivan in collaboration with Vladimir Shulaev at Virginia Bioinformatics Institute are investigating the metabolic response to drug treatment.