How tiny fungal proteins help Histoplasma infect immune cells
Role of secreted cystine-knot proteins in Histoplasma-host interactions
['FUNDING_R01'] · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · NIH-11258875
This work looks at whether small, heat‑resistant 'knottin' proteins made by the fungus Histoplasma help it survive inside immune cells and lead to infection in people.
Quick facts
| Phase | ['FUNDING_R01'] |
|---|---|
| Study type | Nih_funding |
| Sex | All |
| Sponsor | UNIVERSITY OF CALIFORNIA, SAN FRANCISCO (nih funded) |
| Locations | 1 site (SAN FRANCISCO, UNITED STATES) |
| Trial ID | NIH-11258875 on ClinicalTrials.gov |
What this research studies
From a patient perspective, researchers are comparing normal Histoplasma fungi with mutant strains that lack specific small secreted 'knottin' proteins to see how those proteins affect infection. They will use genetic tools like CRISPR to remove or alter the knottin genes, measure which fungal genes are turned on when the fungus shifts to the yeast form at body temperature, and analyze protein interactions and stability in the lab. The team will also test mutant and normal strains in mouse infection models to see whether loss of these proteins reduces the fungus's ability to cause disease. Results aim to reveal whether these knottin proteins are key to how the fungus survives inside macrophages and causes illness.
Who could benefit from this research
Good fit: People with a past history of histoplasmosis or those at higher occupational or environmental risk (for example, frequent exposure to bird or bat droppings) would be most interested, though the work is primarily lab‑based rather than a clinical treatment trial.
Not a fit: Patients with an active histoplasmosis infection are unlikely to receive direct clinical benefit from participating because the grant supports preclinical laboratory and animal research.
Why it matters
Potential benefit: If successful, this could point to new targets for drugs or vaccines to prevent or treat histoplasmosis.
How similar studies have performed: Preliminary mouse experiments already show that mutant fungi lacking individual knottin proteins cause less severe infection in mice, suggesting promise but still early-stage translation to humans.
Where this research is happening
SAN FRANCISCO, UNITED STATES
- UNIVERSITY OF CALIFORNIA, SAN FRANCISCO — SAN FRANCISCO, UNITED STATES (ACTIVE)
Researchers
- Principal investigator: SIL, ANITA — UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- Study coordinator: SIL, ANITA
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.