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 parasites: Entamoeba histolytica, which causes amebic liver abscesses and dysentery, and Toxoplasma gondii, which causes central nervous system infection in AIDS patients. Because of my interest in medical microbiology, we have also worked on better diagnostics for Infectious Diseases in resource-limited settings.

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. There are two morphologically identical species of Entamoeba, Entamoeba histolytica, which can invade and Entamoeba dispar, which cannot. We have shown that cysteine proteinases are key to invasion and have developed a number of new proteinase inhibitors as novel drug therapy. From a collaborative high through put screen of thousands of compounds, we identified an FDA-approved drug, auranofin, which is an oral gold-containing compound that has efficacy against all anaerobic protozoa, Entamoeba, Giardia, and Trichomonas, even those resistant to metronidazole. We are planning a clinical trial of auranofin against E. histolytica and Giardia with collaborators at the International Centre for Research in Diarrhoeal Disease Research, Bangladesh.

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. This project will focus on the role of cysteine proteinases in the pathogenesis of toxoplasmosis. We have cloned and characterized the three major classes of cathepsins, a cathepsin B, L, and three cathepsin Cs and are looking at inhibitors, which target these enzymes. In addition, auranofin also targets the thiol reductase system in T. gondii and my prove to be a new therapeutic agent for toxoplasmosis as well.

Representative Publications

  1. Andrade, R.M., Chapparo, J.D., Capparelli, E., and Reed, S.L. Auranofin is highly efficacious against Toxoplasma gondii in vitro and in an in vivo experimental model of acute toxoplasmosis.  PLOS Negl. Trop. Dis.  8(7):e2973, 2014.
  2. Debnath, A, Parsonage, D., Andrade, R.M., He, C., Cobo, E.R., Hirata, K., Chen, S., Garcia-Rivera, G., Orozco, E., Martinez, M.B., Gunatilleke, S.S., Barrios, A.M., Arkin, M.R., Poole, L.B., McKerrow, J.H. and Reed, S.L.  A high throughput drug screen for Entamoeba histolytica  identifies a new lead and target, Nature Med. 18(6): 956-60. 2012. PMID: 22610278
  3. Cobo, E.R., He, C., Hirata, K., Hwang, G., Tran, U.P., Eckmann, L., Gallo, R.L., and Reed, S.L. Entamoeba histolytica induces intestinal cathelicidins but is resistant to cathelicidin-mediated killing. Infect. Immun. 80(1):143-9, 2012. PMID: 22083705
  4. Lochhead, M.J., Todorof, K., Delaney, M., Ives, J.T., Greef, C., Moll, K., Rowley, K., Vogel, K., Myatt, Zhang, X.Q., Logan, C., Benson, C., Reed, S.L., Schooley, R.T. Rapid multiplexed immunoassay for simultaneous serodiagnosis of HIV-1 and co-infections. J. Clin. Microbiol.,49(10):3584-90, 2011.
  5. He, C., Nora, G.P., Schneider, E.L., Kerr, I.D., Hansell, E., Hirata, K., Gonzalez, D., Sajid, M., Boyd, S.E., Hruz, P., Cobo, E.R., Le, C., Liu, W-T., Eckmann, L., Dorrestein, P.C., Houpt, E.R., Brinen, L.S., Craik, C.S., Roush, W.R., McKerrow, J., and Reed, S.L. A Novel Entamoeba histolytica cysteine proteinase, EhCP4, is key for invasive amebiasis and a therapeutic target. J. Biol. Chem. 285(24):18516-27, 2010.PMID: 20378535
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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, Infectious Diseases, and Medical Microbiology. In 1986 she was appointed Assistant Professor of Medicine in Residence, and was promoted to Professor of Pathology and Medicine by 1998. She has been Director of the Microbiology Laboratory at UCSD Health Systems since 1994.

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, and the UCSD Distinguished Teaching Award.

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