|
||||
|
|
|
|||
 |
 |
|
Drew, MarkMark Drew, Assistant Professor Research Interests The research of my lab focuses on Plasmodium falciparum, the protozoan parasite that causes the most pathogenic form of human malaria. There are over 200 million new clinical cases of malaria each year, with well over 1 million fatalities. It is the leading cause of childhood death by any single infectious agent in the world. Treating this disease requires anti-malarial drugs that are accessible and cost-affordable. Additionally, a continued effort toward drug development is crucial to combat the ongoing threat of drug resistance. My efforts for discovery and development of novel therapeutics to treat infections with P. falciparum are divided into two strategies: In an aim to identify novel structures and/or scaffolds for potential development of therapeutic leads, we are screening chemical compounds for their ability to kill malaria parasites. Toxicity screens are being performed on in vitro cell cultures of P. falciparum in 96 or 384-well plate formats using a new FACSCantoII flow cytometer housed in our lab. Promising compounds are prioritized based on a scoring matrix using criteria such as potency, death-phenotype, and selectivity. These are further characterized through structure-activity analysis and target identification. This work is done in close collaboration with members of the Division of Medicinal Chemistry and Pharmacognosy in the OSU College of Pharmacy. In a target-based approach, we are evaluating a number of parasite-expressed proteases as viable drug targets. Our studies involve the characterization of these enzymes through biochemical, genetic, and cell biological methods. In this effort, we have completed a screen of a library of mechanism-based cysteine protease inhibitors against P. falciparum. Through these studies we have identified compounds that kill parasites at low micromolar concentrations. This approach has allowed us to elucidate the mechanism of activation of the aspartic protease plasmepsins and has uncovered a protease homologous to the yeast autophagy protein, ATG4, which appears to be involved in regulating nutrient acquisition via autophagy in this parasite. We are in the process of conducting experiments to assess the essentiality and cellular function of this putative protease. Selected Publications Liu J, Gluzman I, Drew ME, Goldberg DE. The Role of Plasmodium falciparum Food Vacuole Plasmepsins. J. Biol. Chem., Jan 2005; 280: 1432 – 1437 Drew ME, Banerjee R, Gilbertson SR, Rosenthal PJ, Goldberg DE. Plasmodium food vacuole plasmepsins are activated by falcipains. J. Biol. Chem., May 2008; 283(19):12870-6 |
||
 |
||
 |
 |
|
