Investigators and Program Directors

Research Interests

Using protozoa that are opportunistic pathogens in AIDS patients, and for which no treatment is known, our goals are to identify and characterize unique metabolic pathways in them which may serve as targets for chemotherapy. Specifically, within the Phylum Apicomplexa (which includes species of Cryptosporidium, Cyclospora, Eimeria, Plasmodium, and Toxoplasma), our aim is to understand at the biochemical and molecular level, the expression, regulation, and phylogenetic relatedness of key enzymes controlling parasite metabolism in order to rationally design drugs against them.

Our long range goal is to determine whether C. parvum core metabolism can be exploited for therapeutic purposes. The central hypothesis is that parasite-specific enzymes are compartmentalized within two organelles, the relic mitochondrion and crystalloid body, both of which may be targeted for drug delivery. Core energy metabolism in anaerobic parasites like C. parvum differs from that of humans because they lack typical eukaryotic mitochondria. That is, the relic mitochondrion of C. parvum does not generate ATP by oxidative phosphorylation and has no genome. Instead, it functions solely to synthesize iron sulfur [FeS] cluster proteins. This is important because C. parvum possesses an unique [FeS] fusion enyme, pyruvate:NADP+ oxidoreductase (CpPNO), which is localized within the crystalloid body, an enigmatic organelle located next to the relic mitochondrion and whose function is as yet unknown. The rationale for this research is that once it is known how CpPNO transfers electrons within this organelle, up- or down-regulation of the enzyme can lead to new and innovative therapies for treating cryptosporidiosis. Currently, we are isolating these organelles in order to determine their structure and function using a combination of cryo-electron tomography and proteomics.

The laboratory also performs major investigative research for better clinical diagnosis of human parasites within the State of New York, including PCR and/or Real-time PCR for babesiosis, cryptosporidiosis, as well as chloroquine-sensitive and -resistant malarias. We also serve on the Medical Advisory Board of World's Window, Inc., to provide rapid and specific testing for malaria and other parasites in Zimbabwe, South Africa.

Contact Information

E-mail: keithly@wadsworth.org.