Our laboratory focuses on studying druggable gene targets in the protozoan parasite Trypanosoma brucei. Because T. brucei is amenable to biochemistry, molecular biology, cell biology and chemical biology methodology, it represents an ideal model system for studying eukaryotic cellular pathways.

By studying essential DNA metabolizing genes, we hope to identify differences in the pathways of T. brucei that can be exploited to develop novel drug treatments.

Current Projects:
DNA Ligases
Protein Kinases

Mackey ZB, Koupparis K, Nishino M, McKerrow JH. High Throughput Analysis of an RNAi Library Identifies Novel Kinase targets in Trypanosoma brucei. Chem Biol Drug Des. 2011 Jun 11. doi: 10.1111/j.1747-0285.2011.01156.x. [Epub ahead of print]

Ang KK, Ratnam J, Gut J, Legac J, Hansell E, Mackey ZB, Skrzypczynska KM, Debnath A, Engel JC, Rosenthal PJ, McKerrow JH, Arkin MR, Renslo AR. Mining a cathepsin inhibitor library for new antiparasitic drug leads. PLoS Negl Trop Dis. 2011 May 3;5(5):e1023.

Kerr ID, Wu P, Marion-Tsukamaki R, Mackey ZB, Brinen LS. Crystal Structures of TbCatB and rhodesain, potential chemotherapeutic targets and major cysteine proteases of Trypanosoma brucei. PLoS Negl Trop Dis. 2010 Jun 8;4(6):e701.

Oluwafemi AJ, Okanla EO, Camps P, Muñoz-Torrerob D, Mackey ZB, Chiang PK, Seville S, Wright CW. Evaluation of cryptolepine and huperzine derivatives as lead compounds towards new agents for the treatment of human African trypanosomiasis. Nat Prod Commun. 2009 Feb;4(2):193-8.

Liu CL, Shen CR, Hsu FF, Chen JK, Wu PT, Guo SH, Lee WC, Yu FW, Mackey ZB, Turk J, Gross ML. Isolation and identification of two novel SDS-resistant secreted chitinases from Aeromonas schubertii. Biotechnol Prog. 2009 Jan-Feb;25(1):124-31.

Chen CK, Doyle PS, Yermalitskaya LV, Mackey ZB, Ang KK, McKerrow JH, Podust LM. Trypanosoma cruzi CYP51 inhibitor derived from a Mycobacterium tuberculosis screen hit. PLoS Negl Trop Dis. 2009;3(2):e372. Epub 2009 Feb 3.

Abdulla MH, O'Brien T, Mackey ZB, Sajid M, Grab DJ, McKerrow JH. RNA interference of Trypanosoma brucei cathepsin B and L affects disease progression in a mouse model. PLoS Negl Trop Dis. 2008 Sep 24;2(9):e298.

O'Brien TC, Mackey ZB, Fetter RD, Choe Y, O'Donoghue AJ, Zhou M, Craik CS, Caffrey CR, McKerrow JH. A parasite cysteine protease is key to host protein degradation and iron acquisition. J Biol Chem. 2008 Oct 24;283(43):28934-43. Epub 2008 Aug 13

Doyle PS, Sajid M, O'Brien T, Dubois K, Engel JC, Mackey ZB, Reed S. Drugs targeting parasite lysosomes. Curr Pharm Des. 2008;14(9):889-900. Review.

Mackey ZB, Baca AM, Mallari JP, Apsel B, Shelat A, Hansell EJ, Chiang PK, Wolff B, Guy KR, Williams J, McKerrow JH. Discovery of trypanocidal compounds by whole cell HTS of Trypanosoma brucei. Chem Biol Drug Des. 2006 May;67(5):355-63.