Danielle Alfano
Washington University in St Louis, MO·Microbiology & Immunology·Early-career
Sepsis happens when the body's response to an infection goes wrong and begins damaging its own organs. It is among the leading causes of death worldwide.
- Fields
Microbiology & Immunology
Medicine & Clinical Research
Biology
- Topics
sepsis
endothelium
endothelial injury
- Grants
- 1 known grant, through Jun 2029
What they work on
- Determine the molecular mechanisms by which diverse live pathogens activate endothelial ADAM10, the cell-surface protein that acts as the S. aureus alpha-toxin receptor, using unique mouse lines.
- Characterize the specific ADAM10 substrates, proteins cut and released by ADAM10, that are shed during systemic infection, using proteomic approaches.
- Examine whether an ADAM10 SNP, a single-letter genetic variant, confers increased risk of lethal sepsis, linking host genetics to blood-vessel injury.
More about the research
Decades of work focused on an overactive immune response have produced no new effective therapies. This project looks instead at the endothelium, the cell layer lining blood vessels, which helps control how the body responds to infection and how organs become injured.
Why it matters
Sepsis kills enormous numbers of people and still has no targeted therapy. Clarifying how diverse human pathogens use ADAM10 to injure blood vessels could reveal new strategies to prevent or treat lethal infection, and studying an ADAM10 genetic variant may help explain why some people are at far higher risk of life-threatening sepsis.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Juliane Bubeck Wardenburg
Washington University in St Louis, MO·Microbiology & Immunology
Determine how S. aureus alpha-toxin (Hla) impairs antigen-specific CD4+ T cells in skin infection, examining antigen trafficking, T-cell receptor signaling during infection, and whether T-cell ADAM10 levels predict susceptibility, using cell-type-specific transgenic mice and a human biorepository.
Masanori Matsumoto
University of Illinois Urbana-Champaign, IL·Microbiology & Immunology·Early-career
Use a new atopic dermatitis-like mouse model, with S. aureus applied to the skin, to test whether the Agr quorum-sensing system drives skin inflammation by causing keratinocytes to release alarmin danger signals.
Madison Collins
Montana State University, MT·Microbiology & Immunology
Test the hypothesis that molecules controlled by the S. aureus SaeR/S gene regulatory system disrupt autophagy, a self-digestion process that kills trapped microbes, in human neutrophils after they swallow the bacteria.
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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