Investigating molecular mechanisms that underlie thermal dimorphism and pathogenesis of Histoplasma capsulatum by Sarah Heater

Sarah Heater

UC San Francisco | MJ Whitehouse, MD & Michael Heffernan

It is estimated that every day we inhale thousands of fungal spores—most of these are harmless, but some are able to cause disease. In order to survive in humans, many of these inhaled fungi must first sense that they are inside of a body. My research focuses on how a set of fungi are able to sense body temperature when inhaled, which initiates a drastic change of form and enables these fungi to cause illness.


I study the human fungal pathogens Histoplasma capsulatum, which causes respiratory and systemic illness, and Coccidioides, the causative agent of Valley Fever which is endemic in the Southwestern U.S.. These fungi grow as multicellular root-like hyphae in soil, producing infectious spores. When aerosolized by wind or digging, hyphae and spores can be inhaled by mammals. To cause disease after inhalation, these fungi must sense and respond to body temperature, transitioning to growth as unicellular yeast or spherules. In a laboratory, the shift from environmental temperature to body temperature is sufficient to change morphology and trigger a broad virulence response. The objective of my primary project is to investigate mechanisms of regulation in temperature response pathways in Histoplasma capsulatum with the goal of uncovering a molecular thermometer that triggers morphological changes and virulence in response to temperature. I have identified two candidate molecular thermometers that have compelling similarities with known thermo-sensors in other organisms, and have begun investigating the mechanism by which these molecules are regulated.


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