Research Associate, UCSD
Skaggs School of Pharmacy and Pharmaceutical Sciences
Contact:
My research focuses predominately on the studying of the Clan CA cysteine proteinases, cathepsin B and L. These proteolytic enzymes have been reported to possess a broad range of biological function that encompasses an equally broad spectrum of disease states. These diseases include amongst others, parasitic virulence, cancer, arthritis, and alzheimer’s disease. The biological importance of cathepsins in disease validates the efforts in understanding the fundamental mechanism of action, biological targets and subsequently the development of therapeutic compounds.
My interest in parasitic research began 26 years ago in the research laboratory of Dr. Sharon Reed (UCSD), where our main focus has been investigating the cathepsins and thioredoxin reductase of Entameoba histolytica, the causative agent in amebiasis which afflicts over 40 million individuals every year. Recently, I also joined CDIPD as a molecular biologist involved in the expression and characterization of cathepsins and phosphodiesterases, as well as the drug discovery which targets these virulence factors in numerous neglected tropical diseases.
Additionally, I am the manager for the Dr. McKerrow and Dr. Podust laboratories responsible for maintaining compliance with Environmental, Health and Safety (E,H &S) standards; including safety training, hazardous waste disposal, and general compliance of a safe work environment. I develop and implement standard operating procedures (SOP) for experimental techniques as well as the use and maintenance of key laboratory equipment; act as the liaison regarding the repair and routine maintenance of all laboratory equipment.
PUBLICATIONS
Design of Gallinamide A Analogs as Potent Inhibitors of the Cysteine Proteases Human Cathepsin L and Trypanosoma cruzi Cruzain. J Med Chem. 2019 Oct 24;62(20):9026-9044. doi: 10.1021/acs.jmedchem.9b00294. Epub 2019 Oct 4. Boudreau PD, Miller BW, McCall LI, Almaliti J, Reher R, Hirata K, Le T, Siqueira-Neto JL, Hook V, Gerwick WH.
4-aminopyridyl-based lead compounds targeting CYP51 prevent spontaneous parasite relapse in a chronic model and improve cardiac pathology in an acute model of Trypanosoma cruzi infection. PLoS Negl Trop Dis. 2017 Dec 27;11(12):e0006132. doi: 10.1371/journal.pntd.0006132. eCollection 2017 Dec. Calvet CM, Choi JY, Thomas D, Suzuki B, Hirata K, Lostracco-Johnson S, de Mesquita LB, Nogueira A, Meuser-Batista M, Silva TA, Siqueira-Neto JL, Roush WR, de Souza Pereira MC, McKerrow JH, Podust LM.
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 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.
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.
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.
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.
A unique cysteine proteinase gene of pathogenic Entamoeba histolytica correlates with virulence. Arch Med Res. 1992;23(2):181-2. Reed S, Bouvier J, Hirata K, Que X, Pollack AS, Engel JC, Gillin F, McKerrow JH.