Elizabeth Winzeler, Ph.D.
Global morbidity and mortality from infectious diseases such as tuberculosis (TB) and malaria has increased over the past decade. While such diseases are universally recognized as unpleasant and potentially fatal they also exact heavy tolls on the economies of countries where they are endemic and thus may contribute substantially to global poverty. While there are effective treatments for such neglected diseases, there are significant reasons for continuing to search for new therapies. First of all, microbial resistance has made some of the most effective and inexpensive drug regimes unreliable and dangerous to use on severely ill patients. Second, many existing antimicrobial drugs show toxicity or are too expensive for countries where the per capita income is on the order of hundreds of dollars per year. Our group is working to identify and develop new therapies for malaria using a variety of approaches. First we are working to discover new malaria drug targets though systematic analyses of the genome of the parasite that causes malaria, and through the discovery of genes involved in host-parasite interactions as part of the mouse haplotype project. We are also searching GNF chemical libraries for molecules that prevent the parasite from growing in human red blood cells and are working to develop these leads into new drugs. Through our analyses of parasite diversity we are discovering genes involved in drug resistance and host immune-response evasion. These latter genes are being investigated as potential targets for a malaria vaccine. Finally our lab is interested in developing new systems-based and bioinformatic approaches that may be used to understand the action of biologically-active small molecules that are identified through whole organism screening.
- Plouffe D, Brinker A, McNamara C, Henson K, Kato N, Kuhen K, Nagle A, Adrian F, Matzen JT, Anderson P, et al. In silico activity profiling reveals the mechanism of action of antimalarials discovered in a high-throughput screen. Proc Natl Acad Sci U S A 2008;105(26):9059-64.
- Kato N, Sakata T, Breton G, Le Roch KG, Nagle A, Andersen C, Bursulaya B, Henson K, Johnson J, Kumar KA, et al. Gene expression signatures and small-molecule compounds link a protein kinase to Plasmodium falciparum motility. Nat Chem Biol 2008;4(6):347-356.
- Zhou Y, Ramachandran V, Kumar KA, Westenberger S, Refour P, Zhou B, Li F, Young JA, Chen K, Plouffe D, et al. Evidence-based annotation of the malaria parasite's genome using comparative expression profiling. PLoS ONE 2008;3(2):e1570.
- Young JA, Johnson JR, Benner C, Yan SF, Chen K, Le Roch KG, Zhou Y, Winzeler EA. In silico discovery of transcription regulatory elements in Plasmodium falciparum. BMC Genomics 2008;9:70.