PIPages
Labs

Arturo Casadevall

Johns Hopkins University, MD·Microbiology & Immunology

Fungal infections kill thousands of people with weakened immune systems each year and are notoriously hard to cure. Cryptococcus neoformans, a yeast that can infect the brain, is a major example.

Fields

Microbiology & Immunology

Biochemistry

Medicine & Clinical Research

Topics

Cryptococcus neoformans

cryptococcosis

fungal pathogen

Grants
2 known grants, through Jan 2028

What they work on

  1. Establish how Cryptococcus neoformans melanizes its cell wall, including the vesicle-based pathway (small membrane bubbles) that exports melanin outside the cell.
  2. Determine how neutral lipids stored in lipid droplets influence melanin synthesis and deposition in C. neoformans, using biochemical, cell biology and solid-state NMR approaches.
  3. Establish how melanization subverts interactions between C. neoformans and macrophages, the immune cells that engulf and kill microbes.
  4. Identify small-molecule inhibitors of C. neoformans melanin production and determine their mechanisms of action as potential broad antifungal agents.
  5. Map the catalytic site of monoclonal antibodies that cut the capsular polysaccharide GXM, using site-directed mutagenesis to generate matched antibodies with and without catalytic activity.
  6. Test whether catalytic antibodies clear cryptococcal capsular polysaccharide from tissue in normal and immunodeficient mice, and how this affects fungal cells and protection.

More about the research

It protects itself in two ways: a dark pigment called melanin and a thick sugar coat called a capsule. These projects ask how those defenses work and how they could be disarmed. One studies how the fungus makes and uses melanin. The other develops antibodies that can cut apart the capsule.

Why it matters

Cryptococcosis mainly strikes immunosuppressed people, especially patients with AIDS, and current treatment cannot remove the immune-suppressing capsule material left in tissue. Catalytic antibodies that degrade it could become a new type of antibody therapy for AIDS-associated cryptococcosis. Melanin inhibitors could make fungi easier to treat with existing drugs and could act against many melanin-producing pathogenic fungi.

Known grants

From NIH and NSF research grants. Labs often have other funding we can't see.

The biology of Cryptococcus neoformans melanization

NIH · Feb 2023 – Jan 2028

Exploiting antibody catalysis for treating Cryptococcosis

NIH · May 2021 – Apr 2027

Closest labs

Wendy Watford

University of Georgia, GA·Microbiology & Immunology

Identify which immune cell types are required for protection when CD4+ T cell-deficient mice, a model of AIDS, are vaccinated with ZNF2oe, a harmless filament-forming Cryptococcus strain that overproduces the Znf2 regulator.

Stuart Levitz

University of Massachusetts Chan Medical School, MA·Microbiology & Immunology

Test how well each of seven recombinant cryptococcal proteins, combined with the adjuvant CAF01, protects mice against virulent Cryptococcus strains found around the world.

Ryan Peterson

Texas State University, TX·Microbiology & Immunology

Identify and characterize the copper-binding metallophore that Pseudogymnoascus destructans secretes under copper limitation, testing the hypothesis that it is an opine-based metallophore, a class previously known only in bacteria.

The school

Johns Hopkins University: 100 labs on PI Pages, $4.1B a year on research, 622 research doctorates a year.

More about Johns Hopkins University

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