Patricia Doyle


Research Scientist

M.Sc., University of Buenos Aires (UBA)
Ph.D. LPD, NIAID, NIH
Doctorate in Cell Biology (Honors), Univ. Buenos Aires (UBA)
Fogarty Fellow, LPD, NIAID, NIH

Phone: 415-476-0825
Fax:415-502-8193
patricia.doyle-engel@ucsf.edu

Research Interests

  1. • Trypanosoma cruzi

  2. • Proteases as targets for chemotherapy of parasitic diseases

  3. • Small-molecules as chemotherapeutic agents

  4. • Efficacy of chemotherapeutic agents including protease and cytochrome inhibitors, and anti-carcinogens in cell assays and animal models of Chagas’ disease

  5. • Protease expression, localization, and trafficking in T. cruzi and Leishmania

  6. • Biological role of proteases


Neglected tropical diseases (NTD) affect an estimated one billion people living in the poorest and most marginalized social conditions.  Nevertheless, less than 1% of drugs registered in the past 30 years were for NTDs.  Recent years have seen significant advances in the search for new chemotherapies for these diseases mostly financed by humanitarian non-profit organizations. Our multidisciplinary group at the University of California, San Francisco, focuses on the development of novel chemotherapy for neglected parasitic diseases.  My main interest is Chagas’ disease, caused by the protozoan parasite Trypanosoma cruzi.  We have targeted the major protease cruzain for the development of effective chemotherapeutic agents. Our core evaluates efficacy of compounds provided by numerous collaborators in cell assays and animal models of Chagas’ disease.  Thousands of compound screens led to the identification of K11777, the first new drug-lead for Chagas’ disease in 50 years. Our findings have been extended to other parasitic diseases, including African sleeping sickness and schistosomiasis.

Selected Publications:

Chen C.K., Doyle P.S., Yermalitskaya L.V., Mackey Z.B., Ang K.K., McKerrow J.H., and L.M. Podust. 2009. Trypanosoma cruzi CYP51 Inhibitor derived from a Mycobacterium tuberculosis Screen Hit. PLoS Negl Trop Dis. 3(2): e372

Doyle, P.S., Sajid, M., O’Brien, T., DuBois, K., Engel, J.C., Mackey, Z. B., and S. Reed. 2008. Drugs targeting parasite lysosomes. Current Pharm. Design 14: 889-900

Brak, K., Doyle, P.S., McKerrow, J.H., and J. A. Ellman. 2008. Identification of a New Class of Nonpeptidic Inhibitors of Cruzain. J. Am. Chem.  Society 130(20): 6404-6410

Fricker S.P., Mosi R.M., Cameron B.R., Baird I., Zhu Y., Anastassov V., Cox J., Doyle P.S., Hansell E., Lau G., Langille J., Olsen M., Qin L., Skerlj R., Wong R.S., Santucci Z., McKerrow J.H. 2008.  Metal compounds for the treatment of parasitic diseases.  J Inorg. Biochem. 102(10): 1839-45

Doyle, P.S., Zhou, Y.M., Engel, J.C., and J.H. McKerrow.  2007.  A cysteine protease inhibitor cures Chagas' disease in an immunodeficient-mouse model of infection. Antimicrob. Agents and Chemotherapy 51(11): 3932-3939

Engel, J.C., Doyle, P.S., Hsieh, I., and J.H. McKerrow.  1998.  Cysteine Protease inhibitors cure an experimental Trypanosoma cruzi infection.  J. Exp. Med.  188: 725-734

Engel, J.C., García, C.T., Hsieh, I., Doyle, P.S., and J.H. McKerrow.  2000.  Upregulation of the secretory pathway in cysteine protease inhibitor-resistant Trypanosoma cruzi.  J. Cell Science 113: 1345-1354

Engel, J. C., Doyle, P. S., Palmer, J., Hsieh, I., Bainton, D. F, and J.H. McKerrow.  1998.  Growth arrest of T. cruzi by cysteine protease inhibitors is accompanied by alterations in Golgi complex and ER ultrastructure.  J. Cell Science 111: 597-606