We study soil fungi that cause disease when fungal cells are inhaled by mammalian hosts, including people.
Areas of interest:
Microbial Signal Transduction
How do microbial cells sense temperature?
Thermally dimorphic fungi such as Histoplasma
and Coccidioides species are primary pathogens that cause
disease in both healthy and immunocompromised hosts. These
pathogenic fungi undergo drastic transitions in cell shape and
gene expression when exposed to different temperatures, and host
temperature is the key signal that triggers a developmental
pathway resulting in cell shape changes and virulence gene
expression required to cause disease. We use genetics and
functional genomics to elucidate molecules that sense and
respond to temperature.
How do fungi specify cell fate?
Fungal developmental programs require multiple regulatory
proteins that have been rewired across the fungal kingdom to
respond to different inputs. As experts in transcriptomics, we
study how transcriptional networks and other regulatory modules
function across fungal species to trigger key cell fate
How do fungal pathogens counter the innate immune response?
Histoplasma and Coccidioides species can subvert
the innate immune response to replicate and cause disease. We
study the ability of Histoplasma to evade anti-microbial
defenses and colonize macrophages.
How do intracellular fungi subvert the normal cell biology of the macrophage?
Histoplasma replicates within the macrophage phagosome,
and unknown mechanisms are used to recruit host membrane around
each microbial cell as it divides. We want to understand
how Histoplasma manipulates the fundamental biology of
the host cell.
Mammalian Cell Death
How do intracellular fungi exit their host cell?
We have shown that the ability of Histoplasma to trigger
host cell lysis is dependent on secreted effectors from the
fungus. We study how these effectors trigger cellular stress and
host cell death.