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Contact

 

Sharon Reed

Affiliation: UCSD SOM
Professor, Department of Pathology

slreed@ucsd.edu
Phone: (619)543-6146

Biography

Dr. Reed graduated from Harvard University Medical School and then received her M.Sc. in Clinical Tropical Medicine from the University of London in 1982.

Research Summary

My laboratory focuses on the mechanisms of virulence of two protozoan parasites: Entamoeba histolytica, which causes amebic liver abscesses and dysentery, and Toxoplasma gondii, which causes sever congenital and reactivation diseases in immunocompromised patients with transplants or AIDS.

Although 10% of the world's population is infected with Entamoeba, less than 1% develop invasive disease. The virulence factors of the infecting parasite appear to be very important in determining the outcome of infection. Two morphologically identical species exist, Entamoeba histolytica, which can invade, and Entamoeba dispar, which can not. Cysteine proteinases are important virulence factors, which are encoded by at least seven genes. Noninvasive E. dispar has at least five of the same genes, but releases significantly less cysteine proteinase activity. We are investigating differences in the synthesis and release of cysteine proteinases in E. histolytica and noninvasive E. dispar. We have developed the first vector which will integrate into the E. histolytica genome using pseudotyped retroviruses. We can now take advantage of transgenic amebae expressing different cysteine proteinase genes or antisense RNA, as well as novel new cysteine proteinase inhibitors to further our understanding of key virulence factors of E. histolytica.

Toxoplasmosis is one of the most common parasitic infections of man. The majority of patients have asymptomatic, dormant infection for life, however serious complications result from congenital infection or reactivation disease in immunocompromised patients, particularly those with AIDS. Although a number of drug regimens have been used effectively, all are limited by toxic side effects and life-long suppression is required. Thus, the identification of potential new drug targets is critically important. We have cloned two cysteine proteinase genes from T. gondii, and shown that a cathepsin B, toxopain-1, localizes to the rhoptry organelles, which are critical to invasion. We have inhibited expression of toxopain-1 by expressing antisense and demonstrated the significant effects on infection in a novel new chick model of congenital toxoplasmosis. These studies should not only provide important information about the pathogenesis of one of the most serious opportunistic infections of AIDS patients, but could also establish a role for cysteine proteinase inhibitors as novel new therapeutic agents for toxoplasmosis.

References

References From PubMed (NCBI)

 

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©2008 UCSD/Burnham Molecular Pathology Graduate Program