Makedonka Mitreva
Washington University in St Louis, MO·Microbiology & Immunology
Parasitic worms called nematodes infect billions of people. They cause disabilities such as elephantiasis and river blindness and keep communities trapped in poverty.
- Fields
Microbiology & Immunology
Genetics
Pharmacology
- Topics
lymphatic filariasis
Wuchereria bancrofti
onchocerciasis
- Grants
- 3 known grants, through Jul 2030
What they work on
- Track the reproducing adult female Wuchereria bancrofti worms over time by reconstructing sibling relationships among larvae (microfilariae) from repeated blood samples, using whole-genome sequencing of single larvae.
- Identify the sources of lymphatic filariasis transmission by genomically comparing larvae sampled across locations, and feed these estimates into transmission models that predict the risk and pace of resurgence.
- Design new drugs that kill adult river blindness worms by chemically optimizing HIV protease inhibitors such as ritonavir, lopinavir and nelfinavir that block worm aspartic proteases, a family of protein-cutting enzymes.
- Test in animal models whether moxidectin and emodepside prevent young Onchocerca worms from becoming adults, and model which combined treatment regimens could best speed river blindness elimination in Africa.
- Confirm the worm enzyme targets of lead compounds hitting CPT, mTOR/PI3K and PDE, using purified nematode enzymes, affinity labeling and worms with reduced levels of the target.
- Optimize nematode-selective inhibitors using X-ray structure-based drug design and test the best compounds in hamster and mouse infection models of hookworm (Ancylostoma ceylanicum) and whipworm (Trichuris muris).
More about the research
Global programs fight them by giving whole populations drugs. Yet infections persist or return, and the few available drugs face growing resistance. These projects use genomics, drug discovery and mathematical modeling to answer two linked questions: why do worm infections survive mass treatment, and what new drugs and treatment schedules could finish the job?
Why it matters
Lymphatic filariasis, river blindness and intestinal worm infections affect billions of people, mostly in poor communities, and many in sub-Saharan Africa. Genetic tools that reveal where returning infections come from could help elimination programs decide where and how to watch for resurgence. New drug candidates that kill adult worms or work against many species, along with better treatment schedules, could give these programs tools beyond ivermectin and help counter drug resistance.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Advancing lymphatic filariasis elimination with parasite genomic epidemiology
NIH · Aug 2025 – Jul 2030
Innovative therapeutic strategies to support elimination of river blindness
NIH · Sep 2023 – Aug 2027
Development of small molecule inhibitors of metabolic enzymes as broad spectrum anthelmintic drugs
NIH · Mar 2021 – Feb 2027
Closest labs
Richard Martin
Iowa State University, IA·Pharmacology
Measure whether emodepside potently activates KCNMA1, the human BK potassium channel, in HEK293 and CHO cell lines using whole-cell patch-clamp, to judge its potential for side effects.
Elia D Tait Wojno
University of Washington, WA·Microbiology & Immunology
Test how Notch signaling inside basophils controls where they sit in the large intestine and how they contact CD4+ T cells during Trichuris muris worm infection, including a role for alpha4 integrin.
Clayton Cressler
University of Nebraska-Lincoln, NE·Ecology & Evolution
Test whether positive feedback loops between immune cells and parasitic worms, and among immune cells, create tipping points that send an infection toward rapid clearance or chronic infection.
The school
Washington University in St Louis: 97 labs on PI Pages, $1.2B a year on research, 365 research doctorates a year.
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