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: Haley Cronshaw, hcronshaw@hsph.harvard.edu

B.A.
University of Wisconsin , Madison

Ph.D., 1978
Massachusetts Institute of Technology

Alice and C.C. Wang Award in Molecular Parasitology2022
he American Society for Biochemistry and Molecular Biology

Walter Reed Medal 2021
American Society of Tropical Medicine and Hygiene

Honorary Fellow2019
American Association for the Advancement of Science

Lifetime Achievement Award2018
BioMalPar

Faculty Mentoring Award2016
Committee on the Advancement of Women Faculty (CAWF), Harvard T.H. Chan School of Public Health

Fellow2016
American Society of Tropical Medicine and Hygiene

Joseph Augustin LePrince Medal2015
American Society of Tropical Medicine and Hygiene

Fellow2010
American Academy of Microbiology

Member2004
Institute of medicine of the National Academies

President1998-1999
American Society of Tropical Medicine and Hygiene

Bailey K. Ashford Award1995
American Society of Tropical Medicine and Hygiene

Award in Molecular Parasitology1985-1990
Burroughs Wellcome

Award in Molecular Parasitology1982
Burroughs Wellcome

Fellowship1978-1981
Helen Hay Whitney

Predoctoral Fellowship1973-1978
National Institutes of Health

Fellow1972-1973
Fulbright Foundation

Phi Beta Kappa1972

B.A. with Highest Honors1972
University of Wisconsin, Madison


Bibliography

Genotypic analysis of RTS,S/AS01E malaria vaccine efficacy against parasite infection as a function of dosage regimen and baseline malaria infection status in children aged 5-17 months in Ghana and Kenya: a longitudinal phase 2b randomised controlled trial.

Juraska M, Early AM, Li L, Schaffner SF, Lievens M, Khorgade A, Simpkins B, Hejazi NS, Benkeser D, Wang Q, Mercer LD, Adjei S, Agbenyega T, Anderson S, Ansong D, Bii DK, Buabeng PBY, English S, Fitzgerald N, Grimsby J, Kariuki SK, Otieno K, Roman F, Samuels AM, Westercamp N, Ockenhouse CF, Ofori-Anyinam O, Lee CK, MacInnis BL, Wirth DF, Gilbert PB, Neafsey DE.

Lancet Infect Dis. 2024 May 06. PMID: 38723650

Baseline malaria infection status and RTS,S/AS01E malaria vaccine efficacy.

Juraska M, Early AM, Li L, Schaffner SF, Lievens M, Khorgade A, Simpkins B, Hejazi NS, Benkeser DA, Wang Q, Mercer LD, Adjei S, Agbenyega T, Anderson S, Ansong D, Bii DK, Buabeng PBY, English S, Fitzgerald N, Grimsby J, Kariuki SK, Otieno K, Roman F, Samuels AM, Westercamp N, Ockenhouse CF, Ofori-Anyinam O, Lee CK, MacInnis BL, Wirth DF, Gilbert PB, Neafsey DE.

medRxiv. 2023 Nov 23. PMID: 38045387

Malaria surveillance reveals parasite relatedness, signatures of selection, and correlates of transmission across Senegal.

Schaffner SF, Badiane A, Khorgade A, Ndiop M, Gomis J, Wong W, Ndiaye YD, Diedhiou Y, Thwing J, Seck MC, Early A, Sy M, Deme A, Diallo MA, Sy N, Sene A, Ndiaye T, Sow D, Dieye B, Ndiaye IM, Gaye A, Ndiaye A, Battle KE, Proctor JL, Bever C, Fall FB, Diallo I, Gaye S, Sene D, Hartl DL, Wirth DF, MacInnis B, Ndiaye D, Volkman SK.

Nat Commun. 2023 11 10. 14(1):7268. PMID: 37949851

Two decades of molecular surveillance in Senegal reveal changes in known drug resistance mutations associated with historical drug use and seasonal malaria chemoprevention.

Ndiaye YD, Wong W, Thwing J, Schaffner SS, Tine A, Diallo MA, Deme A, Sy M, Bei AK, Thiaw AB, Daniels R, Ndiaye T, Gaye A, Ndiaye IM, Toure M, Gadiaga N, Sene A, Sow D, Garba MN, Yade MS, Dieye B, Diongue K, Zoumarou D, Ndiaye A, Gomis J, Fall FB, Ndiop M, Diallo I, Sene D, Macinnis B, Seck MC, Ndiaye M, Badiane AS, Hartl DL, Volkman SK, Wirth DF, Ndiaye D.

medRxiv. 2023 Apr 26. PMID: 37163114


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.