Anita Sil
University of California-San Francisco, CA·Microbiology & Immunology
Some fungi in the soil switch body shape when they enter a human lung, and that switch helps them cause disease. Histoplasma capsulatum and Coccidioides (the cause of Valley Fever) are thermally dimorphic fungi, meaning they change form in response to temperature.
- Fields
Microbiology & Immunology
Genetics
Medicine & Clinical Research
- Topics
Histoplasma capsulatum
histoplasmosis
Coccidioides
- Grants
- 5 known grants, through Apr 2030
What they work on
- Define how the Ryp1–4 transcription factors and the heat shock pathway, including the chaperone Hsp90, work together to drive temperature-triggered yeast growth and virulence in Histoplasma capsulatum.
- Determine which genes in a naturally occurring, reversible chromosome duplication speed filament formation, and probe how temperature changes chromatin accessibility in Histoplasma.
- Test how single and multiple knottin proteins (small, highly stable secreted proteins) contribute to Histoplasma virulence, using CRISPR-generated mutants in macrophage and mouse infection models.
- Compare macrophage gene expression after infection with wild-type versus knottin-mutant Histoplasma to see how knottins shape the integrated stress response and the blocking of phagosome maturation.
- Identify where selected knottins localize in infected macrophages and which proteins they bind, to reveal how they work at the molecular level.
- Find Coccidioides genes that control spherule development using genome-wide association studies, transcriptomics and proteomics of spherulation, and drug-repurposing screens for compounds that block spherulation or growth.
- Profile the human immune response to Valley Fever using mass cytometry and single-cell RNA sequencing of lung nodules, and analyze cerebrospinal fluid from patients with coccidioidal meningitis.
- Map the most immunogenic regions of the Coccidioides proteome with phage-display epitope mapping to find antigens with diagnostic potential.
More about the research
They grow as mold-like threads in soil. Once their spores are inhaled, they switch into a form adapted to the body. Histoplasma alone infects about 500,000 people a year in the U.S. The lab studies how these fungi sense the host, which genes and secreted proteins let them take over immune cells, and how the human immune system responds. It uses molecular genetics, genomics and infection models with macrophages (immune cells that engulf microbes) and mice. Its Coccidioides work is part of a multi-project research center.
Why it matters
Histoplasmosis and Valley Fever (coccidioidomycosis) sicken many people, especially where these fungi are common, such as California for Valley Fever. Infections range from silent to pneumonia to deadly meningitis. By finding the fungal genes and secreted proteins that drive disease, and the host responses linked to severe outcomes, this work could reveal new antifungal drug targets, repurposed drugs, and antigen- or biomarker-based diagnostics that close current gaps in diagnosing and treating these infections.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Qian Shen
Rhodes College, TN·Microbiology & Immunology
Genetically and biochemically characterize the putative carbonic anhydrases of Histoplasma capsulatum, enzymes that interconvert CO2 and water with bicarbonate and protons, to learn their role in sensing CO2.
Thomas Patterson
University of Texas at San Antonio, TX·Microbiology & Immunology
Determine whether reduced laboratory susceptibility to azole antifungals predicts poorer treatment response in living hosts, by treating mice with pulmonary and central nervous system coccidioidomycosis caused by susceptible versus resistant Coccidioides isolates.
Vincent Michael Bruno
University of Maryland, Baltimore, MD·Microbiology & Immunology
Determine the role of ANGPTL4, a protein produced downstream of the host hypoxia-response pathway, in Mucorales lung invasion, and test whether blocking it treats mucormycosis in mice.
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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