Dyann F. Wirth
Primary Faculty

Dyann F. Wirth

Richard Pearson Strong Professor of Infectious Diseases

Immunology and Infectious Diseases

dfwirth@hsph.harvard.edu


Overview

Protozoan parasites remain major causes of disease in developing countries throughout the world, yet little is known about the biology or molecular biology of these organisms. The long term goal of this work is to understand basic molecular mechanisms in protozoan parasites with the goal of discovering and applying parasite specific interventions.

The approach my laboratory has taken is to develop methods for molecular genetic manipulation of protozoan parasites in order to begin functional analysis of genes important for parasite virulence, with an emphasis of mechanisms of drug resistance in parasites. Drug resistance poses a particularly difficult problem in developing countries where newer chemotherapeutic agents are often unavailable or too expensive for routine use. Drug resistance is particularly acute in malaria where resistant parasites have spread throughout the endemic world.

Recent evidence from my laboratory and from several other groups worldwide has suggested that a major mechanism of drug resistance in protozoan parasites may be through the expression of a P-glycoprotein type molecule encoded by a multi-drug resistance gene. Genes related to mammalian multi-drug resistance genes have been identified in several protozoan parasites and overexpression of these genes is associated with drug resistance. The immediate goal of the research is to test the hypothesis that these mdr-like genes are indeed the cause of drug resistance in protozoan parasites. This work has been initiated in the Leishmania parasite where my laboratory has previously developed a transfection system, and thus the role of the Leishmania enriettii mdr-like genes can be directly tested.

In parallel, my laboratory has recently developed an analogous transfection system for the malaria parasite. By analyzing these two protozoan systems in parallel, one where the molecular tools are readily available and the other in which drug resistant parasites represent a major and immediate threat to world health, I hope both to understand the mechanism of drug resistance in protozoan parasites and to use this information to develop new approaches to either preventing or reversing drug resistance in these organisms.

Executive Assistant: Jessica Gard, jgard@hsph.harvard.edu

B.A.
University of Wisconsin , Madison

Ph.D., 1978
Massachusetts Institute of Technology

Fellow1972-1973
Fulbright Foundation

Predoctoral Fellowship1973-1978
National Institutes of Health

Award in Molecular Parasitology
Burroughs Wellcome

Award in Molecular Parasitology1985-1990
Burroughs Wellcome

Bailey K. Ashford Award
American Society of Tropical Medicine and Hygiene

Bailey K. Ashford Award
American Society of Tropical Medicine and Hygiene

President1998-1999
American Society of Tropical Medicine and Hygiene

Member
Institute of medicine of the National Academies

Fellow
American Academy of Microbiology

Joseph Augustin LePrince Medal
American Society of Tropical Medicine and Hygiene

Faculty Mentoring Award
Committee on the Advancement of Women Faculty (CAWF), Harvard T.H. Chan School of Public Health

Fellow
American Society of Tropical Medicine and Hygiene

Lifetime Achievement Award
BioMalPar


Bibliography

Adaptive laboratory evolution in S. cerevisiae highlights role of transcription factors in fungal xenobiotic resistance.

Ottilie S, Luth MR, Hellemann E, Goldgof GM, Vigil E, Kumar P, Cheung AL, Song M, Godinez-Macias KP, Carolino K, Yang J, Lopez G, Abraham M, Tarsio M, LeBlanc E, Whitesell L, Schenken J, Gunawan F, Patel R, Smith J, Love MS, Williams RM, McNamara CW, Gerwick WH, Ideker T, Suzuki Y, Wirth DF, Lukens AK, Kane PM, Cowen LE, Durrant JD, Winzeler EA.

Commun Biol. 2022 02 11. 5(1):128. PMID: 35149760

Chemogenomics identifies acetyl-coenzyme A synthetase as a target for malaria treatment and prevention.

Summers RL, Pasaje CFA, Pisco JP, Striepen J, Luth MR, Kumpornsin K, Carpenter EF, Munro JT, Plater A, Punekar AS, Shepherd AM, Shepherd SM, Vanaerschot M, Murithi JM, Rubiano K, Akidil A, Ottilie S, Mittal N, Dilmore AH, Won M, Mandt REK, McGowen K, Owen E, Walpole C, Llinás M, Lee MCS, Winzeler EA, Fidock DA, Gilbert IH, Wirth DF, Niles JC, Baragaña B, Lukens AK.

Cell Chem Biol. 2022 02 17. 29(2):191-201.e8. PMID: 34348113

The Plasmodium falciparum ABC transporter ABCI3 confers parasite strain-dependent pleiotropic antimalarial drug resistance.

Murithi JM, Deni I, Pasaje CFA, Okombo J, Bridgford JL, Gnädig NF, Edwards RL, Yeo T, Mok S, Burkhard AY, Coburn-Flynn O, Istvan ES, Sakata-Kato T, Gomez-Lorenzo MG, Cowell AN, Wicht KJ, Le Manach C, Kalantarov GF, Dey S, Duffey M, Laleu B, Lukens AK, Ottilie S, Vanaerschot M, Trakht IN, Gamo FJ, Wirth DF, Goldberg DE, Odom John AR, Chibale K, Winzeler EA, Niles JC, Fidock DA.

Cell Chem Biol. 2022 05 19. 29(5):824-839.e6. PMID: 34233174


News

Malaria expert predicts vaccine will spur innovation

In October, the World Health Organization (WHO) for the first time recommended a broad rollout of a vaccine that protects against Plasmodium falciparum, the deadliest malaria parasite globally and the most prevalent in Africa.

Stephen Marks, Dyann Wirth named AAAS Fellows

Professors Stephen Marks and Dyann Wirth of Harvard T.H. Chan School of Public Health have been named Fellows of the American Association for the Advancement of Science (AAAS). Marks, François-Xavier Bagnoud Professor of Health and Human Rights in…