DEPARTMENT OF PATHOLOGY

Sharon L. Reed, M.D.

Sharon L. Reed, M.D.

  • Professor
  • Director of the Clinical Microbiology Laboratory
  • M.D. - Harvard University
  • Residency Training: Peter Bent Brigham Hospital Boston, Massachusetts
  • Clinical Specialty: Comparative Physiology

Research Interests

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.

Representative Publications

  1. Shimizu, C., Shike, H., Baker, S.C., Garcia, F., van der Hoek, L., Kuijpers, T.W., Reed, S.L., Rowley, A.H., Shulman, S.T., Talbot, H.K.B., Williams, J.V., Burns, J.C. Human coronavirus NL-63 is not detected in the respiratory tracts of children with acute Kawasaki Disease, Journal of Infectious Diseases. 192(10), 2005. (pp. 1767-71)
  2. Cachay, E., Mathews, W.C., Reed, S.L., Swancutt, M.A., Fierer, J. Gonococcal meningitis diagnosed by DNA amplification: Case report and review of the literature. AIDS Patient Care and STDs, in press, 2006
  3. Reed, S.L. Entamoeba histolytica and other intestinal amoebae, In Infectious Diseases Gorbach, S.L., Bartlet, J.G. and Blacklow, N.R., eds. Philadelphia: W.B. Saunders Co., 2006. Book Chapter, (pp. 2393-2399).
  4. Reed, S.L. and Davis, C.E. Laboratory diagnosis of parasitic infections, In Harrison's Principles of Internal Medicine Fauci, A.S., Kasper, D.L., Braunwald, E., Hauser, S.L., Longo, D.L., Jameson, J.L., and Loscalzo, J., eds. New York: McGraw-Hill Co., in press, 2006. Book Chapter
  5. Reed, S.L. Amebiasis and infection with free-living amebas, In Harrison's Principles of Internal Medicine Fauci, A.S., Kasper, D.L., Braunwald, E., Hauser, S.L., Longo, D.L., Jameson, J.L., and Loscalzo, J., eds. New York: McGraw-Hill Co., in press, 2006. Book Chapter
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Biography

Dr. Reed received her Bachelor of Science degree in Biology from Stanford, her Doctor of Medicine degree from Harvard, and her Master of Science degree in Tropical Medicine from the London School of Hygiene and Tropical Medicine (London, England). She completed her internship and residency in Internal Medicine at UCSD and a fellowship in Infectious Diseases at UCSD. She is board certified in Internal Medicine and in Infectious Diseases. In 1986 she was appointed Assistant Professor of Medicine in Residence, and was promoted to Professor of Pathology and Medicine by 1998.

Her numerous honors include being a Westinghouse Science Talent Search Finalist, recipient of a Bank of America Giannini Foundation Fellowship, the Southern California American College of Physician's Governor's Trophy, the American College of Physicians National Associates Research Award, and the Lucille P. Markey Scholar Award in Biomedical Sciences.

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