
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)