SharonReed 185x245Professor, UCSD

Department of Pathology

Director of the Clinical Microbiology Laboratory

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Follow me: http://pathology.ucsd.edu/faculty/reed.htm

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.

We collaborate with CDIPD personnel studying compounds that are active versus Entamoeba histolytica and Giardia lamblia. Together we discovered Auranofin as a repurposed drug for the treatment of amebiasis. I am directing a clinical trial in Bangladesh studying the effect of Auranofin versus both Amoeba and Giardia.

PUBLICATIONS

X-ray structures of thioredoxin and thioredoxin reductase from Entamoeba histolytica and prevailing hypothesis of the mechanism of Auranofin action. J Struct Biol. 2016 May;194(2):180-90. doi: 10.1016/j.jsb.2016.02.015. Epub 2016 Feb 12. Parsonage D, Sheng F, Hirata K, Debnath A, McKerrow JH, Reed SL, Abagyan R, Poole LB, Podust LM.

Synthesis and Evaluation of Oxyguanidine Analogues of the Cysteine Protease Inhibitor WRR-483 against Cruzain. ACS Med Chem Lett. 2016 Jan 14;7(1):77-82. doi: 10.1021/acsmedchemlett.5b00336. Jones BD, Tochowicz A, Tang Y, Cameron MD, McCall LI, Hirata K, Siqueira-Neto JL, Reed SL, McKerrow JH, Roush WR.

Hsp90 inhibitors as new leads to target parasitic diarrheal diseases. Antimicrob Agents Chemother. 2014 Jul;58(7):4138-44. doi: 10.1128/AAC.02576-14. Epub 2014 May 12. Debnath A, Shahinas D, Bryant C, Hirata K, Miyamoto Y, Hwang G, Gut J, Renslo AR, Pillai DR, Eckmann L, Reed SL, McKerrow JH.

A reprofiled drug, auranofin, is effective against metronidazole-resistant Giardia lamblia. Antimicrob Agents Chemother. 2013 May;57(5):2029-35. doi: 10.1128/AAC.01675-12. Epub 2013 Feb 12. Tejman-Yarden N, Miyamoto Y, Leitsch D, Santini J, Debnath A, Gut J, McKerrow JH, Reed SL, Eckmann L.

Reprofiled drug targets ancient protozoans: drug discovery for parasitic diarrheal diseases. Gut Microbes. 2013 Jan-Feb;4(1):66-71. doi: 10.4161/gmic.22596. Epub 2012 Nov 8. Review. Debnath A, Ndao M, Reed SL.

A high-throughput drug screen for Entamoeba histolytica identifies a new lead and target. Nat Med. 2012 Jun;18(6):956-60. doi: 10.1038/nm.2758. Debnath A, Parsonage D, Andrade RM, He C, Cobo ER, Hirata K, Chen S, García-Rivera G, Orozco E, Martínez MB, Gunatilleke SS, Barrios AM, Arkin MR, Poole LB, McKerrow JH, Reed SL.

Entamoeba histolytica induces intestinal cathelicidins but is resistant to cathelicidin-mediated killing. Infect Immun. 2012 Jan;80(1):143-9. doi: 10.1128/IAI.05029-11. Epub 2011 Nov 14. Cobo ER, He C, Hirata K, Hwang G, Tran U, Eckmann L, Gallo RL, Reed SL.

A novel Entamoeba histolytica cysteine proteinase, EhCP4, is key for invasive amebiasis and a therapeutic target. J Biol Chem. 2010 Jun 11;285(24):18516-27. doi: 10.1074/jbc.M109.086181. Epub 2010 Apr 8. He C, Nora GP, Schneider EL, Kerr ID, Hansell E, Hirata K, Gonzalez D, Sajid M, Boyd SE, Hruz P, Cobo ER, Le C, Liu WT, Eckmann L, Dorrestein PC, Houpt ER, Brinen LS, Craik CS, Roush WR, McKerrow J, Reed SL.

Use of recombinant Entamoeba histolytica cysteine proteinase 1 to identify a potent inhibitor of amebic invasion in a human colonic model. Eukaryot Cell. 2007 Jul;6(7):1130-6. Epub 2007 May 18. Meléndez-López SG, Herdman S, Hirata K, Choi MH, Choe Y, Craik C, Caffrey CR, Hansell E, Chávez-Munguía B, Chen YT, Roush WR, McKerrow J, Eckmann L, Guo J, Stanley SL Jr, Reed SL.

A phagocytosis mutant of Entamoeba histolytica is less virulent due to deficient proteinase expression and release. Exp Parasitol. 2007 Feb;115(2):192-9. Epub 2006 Sep 20. Hirata KK, Que X, Melendez-Lopez SG, Debnath A, Myers S, Herdman DS, Orozco E, Bhattacharya A, McKerrow JH, Reed SL.

An unusual surface peroxiredoxin protects invasive Entamoeba histolytica from oxidant attack. Mol Biochem Parasitol. 2005 Sep;143(1):80-9. Choi MH, Sajed D, Poole L, Hirata K, Herdman S, Torian BE, Reed SL.

A surface amebic cysteine proteinase inactivates interleukin-18. Infect Immun. 2003 Mar;71(3):1274-80. Que X, Kim SH, Sajid M, Eckmann L, Dinarello CA, McKerrow JH, Reed SL.

Cysteine proteinases from distinct cellular compartments are recruited to phagocytic vesicles by Entamoeba histolytica. Mol Biochem Parasitol. 2002 Jan;119(1):23-32. Que X, Brinen LS, Perkins P, Herdman S, Hirata K, Torian BE, Rubin H, McKerrow JH, Reed SL.

Degradation of bovine complement C3 by trichomonad extracellular proteinase. Vet Immunol Immunopathol. 2001 Jan 10;78(1):83-96. Kania SA, Reed SL, Thomford JW, BonDurant RH, Hirata K, Corbeil RR, North MJ, Corbeil LB.

L6: a proteinase- and phagocytosis-deficient mutant of Entamoeba histolytica. Arch Med Res. 2000 Jul-Aug;31(4 Suppl):S237-8. No abstract available. Carpeniseanu S, Hirata K, Que X, Orozco E, Reed SL.

Homology modeling of Entamoeba histolytica cysteine proteinases reveals the basis for cathepsin L-like structure with cathepsin B-like specificity. Arch Med Res. 2000 Jul-Aug;31(4 Suppl):S63-4. No abstract available. Brinen LS, Que X, McKerrow JH, Reed SL.

Pantropic retroviral vectors mediate gene transfer and expression in Entamoeba histolytica. Mol Biochem Parasitol. 1999 Apr 30;99(2):237-45. Que X, Kim D, Alagon A, Hirata K, Shike H, Shimizu C, Gonzalez A, Burns JC, Reed SL.

Thiol proteinase expression and pathogenicity of Entamoeba histolytica. J Clin Microbiol. 1989 Dec;27(12):2772-7. Reed SL, Keene WE, McKerrow JH.

Cleavage of C3 by a neutral cysteine proteinase of Entamoeba histolytica. J Immunol. 1989 Jul 1;143(1):189-95. Reed SL, Keene WE, McKerrow JH, Gigli I.