Bryan Greenhouse
University of California-San Francisco, CA·Microbiology & Immunology·Early-career
People who live in places with intense malaria transmission eventually become resistant to getting sick, but it takes years of repeated infections to get there. One reason is that the parasite Plasmodium falciparum keeps changing a protein it displays on the surface of infected red blood cells.
- Fields
Microbiology & Immunology
Public Health & Epidemiology
Genetics
- Topics
malaria
Plasmodium falciparum
PfEMP1
- Grants
- 4 known grants, through Jul 2031
What they work on
- Determine how a person's existing anti-PfEMP1 antibodies and the var genes a parasite first switches on together shape the outcome of new Plasmodium falciparum infections, using plasma, RNA sequencing and clinical records from a Ugandan cohort.
- Test whether antibody pressure drives var gene switching during long-lasting, symptom-free infections and whether particular antibody responses predict a person clearing the parasite on their own.
- Build a PhIP-seq array, which displays short parasite protein fragments on viruses to see which antibodies bind, that samples the full global diversity of PfEMP1 at epitope-level resolution, validated with monoclonal antibodies and immune sera.
- Expand var gene reference diversity by de novo assembly of sequences from all publicly available P. falciparum whole genomes plus newly generated sequence data, using the lab's short-read assembly method.
- Profile how anti-PfEMP1 antibody responses accumulate from infancy to adulthood by applying PhIP-seq to cross-sectional and longitudinal time points from existing Ugandan cohort samples.
- Develop bioinformatic pipelines and data-sharing tools for targeted amplicon sequencing of eukaryotic pathogens, handling the mixed-clone infections and recombination that break tools designed for viruses and bacteria.
- Create a modular statistical toolkit, plus harmonized genomic, epidemiological and clinical data standards, for population-genetic and epidemiologic analyses of pathogens such as P. falciparum.
- Characterize the pathogens causing non-malarial febrile illness in Uganda and the transmission of respiratory pathogens in an urban immigrant community in San Francisco, using multi-pathogen surveillance methods.
- Establish an interactive online training platform in genomic epidemiologic analysis to extend existing workshops and longitudinal training programs for African scientists.
More about the research
That protein, called PfEMP1 (P. falciparum erythrocyte membrane protein 1), sticks infected cells to blood vessel walls so the spleen cannot filter them out. Each parasite carries about 60 interchangeable "var" genes encoding different PfEMP1 versions and switches between them to stay ahead of the antibodies the host makes. Work here asks which antibody responses against PfEMP1 actually protect people, builds the tools needed to measure those responses at scale, and develops the software other scientists need to analyze parasite genetic data. A long-running cohort of children and adults in Uganda, with clinical records, stored blood plasma and frozen parasites, anchors most of the projects.
Why it matters
Malaria remains a leading cause of illness and death in endemic countries, and the long, silent infections that this work targets are the main engine of continued transmission. Pinpointing which PfEMP1 regions protective antibodies recognize could supply targets for vaccines or monoclonal antibody treatments aimed at severe and placental malaria. The shared software and data standards could make parasite genomic data usable for routine surveillance of drug resistance and transmission, and the training components build analysis capacity among scientists in affected countries.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Longitudinal evaluation of interactions between variable PfEMP1 virulence genes, the anti-PfEMP1 antibody repertoire, and outcomes of naturally occurring Plasmodium falciparum infections
NIH · Aug 2026 – Jul 2031
Mentoring translational scientists in international infectious disease research
NIH · Jan 2019 – Dec 2028
Comprehensive, high-resolution arrays to trace the development of antibody responses to variant Plasmodium falciparum antigens in naturally exposed cohorts
NIH · Aug 2025 – Jul 2027
Closest labs
Jessica Briggs
University of California-San Francisco, CA·Public Health & Epidemiology·Early-career
Genotype every Plasmodium falciparum infection in a Ugandan birth cohort of 924 children to estimate the molecular force of infection (the rate at which new parasite clones establish infection) and compare children given DP chemoprevention with those given placebo.
Evelien Bunnik
University of Texas Health Science Center at San Antonio, TX·Microbiology & Immunology
Identify which atypical B cell subsets are linked to protection against malaria, using spectral flow cytometry on malaria-experienced children matched for age and exposure but differing in immunity.
Cristian Koepfli
University of Notre Dame, IN·Public Health & Epidemiology
Sequence more than 1,000 Plasmodium falciparum and more than 800 Plasmodium vivax samples collected since 2019 in the Ethiopian highlands to distinguish imported from locally transmitted infections and test whether imported parasites spread locally.
The school
University of California-San Francisco: 89 labs on PI Pages, $2.1B a year on research, 164 research doctorates a year.
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